RRP Task Force Minutes September 22, 2008
AAO-HNS meeting Chicago, Illinois
Sheraton Chicago Erie Room
Craig Derkay, Richard Smith, Stephen Conley, David Tunkel, Brian Wiatrak, Seth Pransky, Scott McMurray, Jerry Thompson, Matt Brigger, Adam Klein, Karen Zur, Shirley Pignatori, Juliana Sato, Farrel Buchinsky, Mark Gerber and Nancy Bauman
I. Members introduced themselves, updated contact information and approved minutes from our meeting in Orlando from May 2008.
II. The Chair discussed his efforts to arrange for this meeting to be available by teleconference so that members unable to travel to Chicago would have an opportunity to participate. Hotel and financial obstacles were discussed. Dr. Buchinsky recommended a future solution to the problem utilizing a hook-up through his laptop computer with Skype that will provide both audio and video teleconferencing for the cost of a wireless internet connection in the conference room. The group endorsed this approach and will endeavor to have this in place for the May meeting in Seattle, Washington.
III. Old Business
A. Reviews of ongoing studies
1. Serology in RRP (SyRRyuP). Dr. Buchinsky related his progress (about 25 current patients enrolled) and the steps needed to become EITHER a participating site or to directly enroll your patients through his institution. After email distribution of these minutes, Dr. Buchinsky will attach the google document links to these minutes to help centers get started.
He also discussed collaboration with his European and Canadian counterparts to enroll patients outside of the US using a similar protocol.
2. PDL multi-site study: Dr, Brigger related the progress of this study with concerns with slow patient enrollment and the possibility of the sites having to return the PDL lasers to Kay Pentax.
3. RRP Genetics Study: Dr. Buchinsky updated the group on his progress (310 probands with a goal of around 300 more) and received advice regarding comparisons with a control group for making genetic comparisons.
4. Celebrex: Dr. Derkay distributed information prepared by Bettie Steinberg regarding the Celebrex study sponsored by LIJ and NIH. Dr. Pransky, who serves on the DSMB for the study, encouraged the group to refer their adult and pediatric patients to regional centers or to contact Dr. Steinberg to become a participating center. Dr. Klein announced that Emory has recently finished submitting the necessary IRB paperwork to begin enrolling patients. Information on this will be attached to these minutes.
5. Merck-sponsored Incidence and prevalence study: Dr. Derkay announced that Merck is working with a private research group to update the national estimates of RRP incidence and prevalence.
B. Review of recent publications
1. RRP reviews that have either recently been published or are scheduled to be in print before the next Task Force meeting include articles in Laryngoscope, Current Opinion, Expert Opinion and Otolaryngology Clinics of North America.
IV. New business
A. A letter was distributed to the group from the International RRP ISA center and the RRP Foundation (via Michael Green and Bill Stern) requesting the Task Force to issue a public statement recommending that research into the use of Artemisinin and its analogues be moved toward the top of any short list of research initiatives. After discussion, the group elected to contact Dr. Richard Schlegel and ask for him to make a 5-10 minute presentation to the Task Force at its May meeting regarding his work in this area. Additionally, Dr. Wiatrak volunteered to try and put Dr. Schlegel in touch with Dr. Tom Broker to review the available data and suggest further applications for translational research involving RRP.
B. Dr. Wiatrak made a brief presentation to the group regarding advances in adjuvant therapies covering Pegasys (a new formulation of interferon alpha that is being widely used to treat Hepatitis C and cms100 (an anti-smallpox DS DNA experimental drug that is a lipid derivative of Cidofovir and could be administered orally). Dr. Wiatrak will try and arrange for the lead investigator, Neal Frazier, to address the Task Force at one its upcoming meetings on this new formulation (predicted to be 3-4 years away from approval).
C. HPV sub-typing: The commercially available Roche Linear array test is now slated for becoming available in 2009.
D. A helpful discussion took place among the members regarding innovations in surgical instruments and lasers for use in RRP patients. This included a few “tricks of the trade” with respect to the coblator, flexible CO2 laser, PDL and KTP-PDL lasers.
E. Therapeutic use of Gardasil: The group discussed the pros and cons of administering Gardasil to RRP patients outside of a clinical protocol and resolved to try and hold off on this approach until after preliminary data from the SyRRyuP study becomes available.
V. Upcoming meetings.
A. Dr. Pransky announced his intention to put on “Endoscopy Day” in San Diego the Friday prior to the AAO_HNS 2009 meeting in October with a section theme of updates on RRP treatment.
B. The RRPF and International ISA may be planning a “stand-alone” session in the coming months. Information will be distributed regarding this when it becomes available.
There being no further business, the meeting was adjourned at 1110am. The next scheduled meeting of the RRP Task Force will likely take place in Seattle, Washington over the Memorial Day weekend, May 22-25, 2009.
Craig Derkay, MD
Chair, RRP Task Force
RRP Task Force Meeting
Staged in conjunction with SENTAC December 1, 2007
Members in attendance:
(Brian Wiatrak by phone)
The meeting was called to order around 530pm.
The purpose of this meeting was outlined in a series of emails prior to the meeting to attempt to prioritize the Task Force’s resources with regard to support of clinical research involving RRP.
Lengthy discussion took place with regard to cataloguing the current RRP projects known to the Task Force. I will attempt to summarize these below. Ideas were floated along two avenues: to publicize this list (perhaps in the Bulletin) so that clinicians around the country can provide suitable patients; to survey the clinicians on the Task Force (through Survey Monkey) regarding their current patient loads with respect to the severity of disease, adjuvants being utilized, availability of research nurses and ease of working with local vs. national IRB’s.
The current list of known/proposed research is below:
1. The CDC has contacted the Task Force with an interest in reviving the RRP Registry as part of a long-term evaluation of the effect of the HPV vaccine on the incidence and prevalence of RRP in the US. The renewed registry will be organized through the STD branch of CDC but will utilize the help of Beth Unger. It will likely focus on a half-dozen geographically distinct medical communities and likely will begin in the Atlanta metropolitan area. This endeavor will require cooperation with the Task Force and was deemed to be a priority.
2. Along a similar line, Merck is launching an effort to measure the number of prevalent and incident cases in the US utilizing insurance databases. No Task Force resources are anticipated.
3. Paolo Campisi and colleagues in Canada are in the midst of organizing a Canadian RRP registry. Peter Bull is making similar efforts in Europe. No specific Task Force resources are involved aside from the provision of clinical information from the practices at Toronto and Vancouver.
4. A multi-center evaluation of the Pulse Dye Laser for treatment of RRP in children with an eye towards evaluating the effects on the children’s voice is taking place at UAB, Mass Eye and Ear, San Diego and Cincinnati.
5. LIJ has recently opened up the Celebrex study to include children. They are currently enrolling at 5 sites that include adults and children.
6. Farrel Buchinsky at Allegheney General in Pittsburgh continues to search for the genes responsible for susceptibility to RRP. He continues to recruit patients and centers with the assistance of the Task Force.
7. A large-scale attempt to measure the anti-HPV 6 and 11 antibody titers in a cohort of RRP patients is being undertaken in conjunction with Farrel Buchinsky’s study supported by Merck. The idea is to identify if the HPV vaccine may be of a therapeutic benefit to a cohort of RRP patients if their native antibody response to the virus is impaired. This study will likely require cooperation from the Task Force to logistically inform patients of the steps necessary to participate. It would be desirable to get these assays performed before patients are given vaccine outside of a research protocol so that information can be gleaned from the effects of the vaccine on antibody levels and clinical course.
8. Potential studies of the HPV vaccine in susceptible populations have been discussed. These would include: patients currently in remission; pregnant mothers with active condylomata or abnormal pap smears; neonates born to mothers with recognized HPV disease. The former would require cooperation with the Task Force to identify the eligible patients while the latter two would require cooperation with our OB-Gyn and neonatology colleagues.
9. New variations on LiVLP HPV vaccines are in the development stage to include additional subtypes of HPV, while the bivalent vaccine produced by GSK (Ceravix) is being evaluated by the FDA. Effects on RRP and availability for study are yet to be determined.
10. HspE7: Nventa has purchased the patents from Stressgen and is planning to revive its investigation into the benefits of this drug for treating HPV-related disease. The company intends to go back to the FDA with a proposal after standardizing the manufacturing process but will likely start back with CIS first before studying its effect in RRP. I suspect that this will be several years off.
11. Renewed interest in the Mumps/MMR vaccine has arisen. No formal proposals are out there for a clinical study.
12. Likewise, Cidofovir continues to be the most frequently utilized adjuvant therapy being used off-label. There are currently no blinded, placebo-controlled studies being planned or executed.
13. Dr. Schlegel at Georgetown is studying Artemissen though no clinical trial has been organized despite the potential for funding through the RRP-ISA.
No firm decisions were reached regarding prioritization.
The Task Force discussed the potential for conflict of interest with Industry representatives attending its meetings and resolved to limit their attendance to “by invitation” when it is deemed to be helpful to have them present.
Given the smaller than usual attendance at this special meeting, it was decided to circulate these minutes among the Task Force members and to proceed with a resource survey of sites. Ongoing cooperation will continue with the established projects and assistance will be offered as requested for the time being for additional projects as they come together.
The meeting was adjourned at 645pm.
The next meeting of the RRP Task Force will take place in conjunction with ASPO in Orlando, Florida. The tentative date will be Friday May 2, 2008 with exact location, time and date to follow.
Craig Derkay, MD
Chairman, RRP Task Force
RRP Task Force Minutes Monday September 17, 2007
Renaissance Hotel, Room 6
Members in Attendance:
Craig Derkay, MD
Farrel Buchinsky, MD
Jerry Thompson, MD
Karen Zur, MD
Stephen Conley, MD
Rose Mary Stokes, MD
Seth Pransky, MD
Nancy Bauman, MD
Keith Trimble, MD
Brian Wiatrak, MD
Andy Inglis, MD
Marshall Smith, MD
Guests: Kevin Kelly, Richard Haupt, MD, Soura Bhattacharyya
I. Members introduced themselves around the table.
II. Minutes from San Diego Task Force meeting approved
III. Old Business
A. Reviewed Dessert Symposium from Sunday evening. Attendance estimated at 400 at its peak. Merck and AAO-HNS acknowledged and thanked for their support.
B. RRP Focus Group meeting from Saturday discussed. Well-attended and very productive discussions. Medtronics acknowledged for their support. Bill Stern spoke of the desire to identify and fund a center to pursue a treatment regimen for RRP patients with distal (pulmonary) disease spread. Dr Thompson from St. Judes spoke of the possibility of doing this through his institution with Task Force support. Dr. Pransky asked to keep Dorothy Wiley from UCLA involved in planning this study. More to follow!
C. Clinical Controversies: Cidofovir—after a long period of waiting with reshuffling of the editors, the manuscript has been processed and should be able to be published in the next 12 months.
IV. Update on HPV Vaccine efforts
A. Dr Derkay speaking in Chicago tomorrow to ICAAC researchers
B. Drs Derkay and Pransky working with SCI-Med to produce a slide deck on RRP for OB-Gyn and primary care physicians
C. Dr Derkay working with Merck on a worldwide incidence and prevalence estimate of RRP burden of disease
D. Dr. Buchinsky reported on planning efforts along with Dalya Gurus from Merck to perform a serologic study looking at existing anti-HPV 6 and 11 antibody levels in a wide variety of RRP patients to ascertain whether a therapeutic role may exist for Gardasil. International effort with Sanofi-Aventis also coordinated by Dalya.
E. Dr Haupt spoke regarding Merck’s interest in working with RRP researchers to define a role for Gardasil in RRP (prevention and/or therapeutics) Merck is currently legally limited in what it can say on its website and in public forums about this role until the research has been done and the FDA “labels” the vaccine accordingly.
Questions rose regarding boys: this will be case-driven and most likely will not be acted upon by the FDA until at least late 2008 (along with the 23-45 year old female data). Not anticipating action on behalf of the FDA till 2009 regarding re-labeling.
F. Task Force suggested expanding the discussion to colleagues in Pediatrics via the AAP, Family medicine, OB-Gyn and Infectious disease through scientific presentations at their annual/regional meetings. Various Task Force members will initiate actions over the next year to help bring this about.
G. Handout distributed by Dr. Buchinsky on behalf of Michael Green and the RRP ISA regarding their proposal to fund a multi-center combined trial of Artemisinin plus Gardasil.
V. Research initiatives
A. HspE7 briefly discussed. Nventa is planning to start over with genital HPV studies and not likely to investigate its role with RRP for several years.
B. Celebrex study DSMB meeting this week in DC with Dr. Pransky acting as Otolaryngology monitor. Dr Derkay also involved as FDA advisor. Preliminary data suggests delay efficacy and approval for entering children appears imminent.
C. Dr. Trimble reported on the progress of the Canadian RRP registry.
D. Multi-center Pulse Dye Laser treatment study at UAB, Boston, Cincinnati and San Diego discussed.
E. Dr Buchinsky updated the group on the progress made in identifying potential genes involved with RRP susceptibility (over 250 patients enrolled now!)
F. Group discussed at some length the desirability of the RRP Task Force to identify worthy RRP research efforts and helps facilitate recruitment of patients and additional centers for the interested PI’s.
VI. Dr Wiatrak discussed the role of HPV sub typing. The Task Force will continue to defer on making the recommendation of universal sub typing at the time of diagnosis until the commercially available assay gets FDA approval.
VII. Future meetings
A. COSM/ASPO this year will be May2-4, 2008 in Orlando. Dr. Derkay will attempt to secure a room at a convenient time for participants.
B. Dr Pransky may try and organize an RRP session to take place in Milwaukee, WI the first weekend in December in conjunction with this year’s SENTAC meeting to further the discussion regarding prioritizing RRP research initiatives.
There being no further time or new business to discuss the meeting was adjourned at 1245pm.
Craig Derkay, MD
Chairman, RRP Task Force
April 24, 2007
Re: Prepared Statement (RRP ISA) Written in Advance of the 4/27/07 Meeting of the RRP Taskforce
As RRP ISA’s Executive Director, I have reluctantly decided to prepare a written statement of issues rather than incurring the expense of traveling to San Diego for a meeting of only an hour’s duration where key presenters (Merck, for example) are not even going to be present. I have previously asked for a slot on the agenda, and Dr. Derkay has agreed. In lieu of our presence at this meeting, I am asking that this prepared statement be read.
First of all, I would like to thank all of you who actually showed up today. It is important, however, to hear from the advocate groups. They are not just ancillary footnotes, just as the RRP Taskforce is not just a footnote to an otherwise jammed schedule of other interests. It is at the Taskforce that we network and share new ideas. I believe that longer meetings need to be convened on at least a twice a year basis.
This brings me to the second point of this prepared statement. Merck was scheduled to present today on what I understand may be the first of several proposed studies. Before the Taskforce signs off on any resolutions on this matter, either from Merck or from those who are not affiliated with Merck, I would like to offer the following points for your consideration.
My understanding is that a study may be proposed here that may lead to other studies, some of them possibly using Gardasil itself, if the data from the initial study confirms that RRP patients tend to have relatively low titers of neutralizing antibodies against HPV. I’m fine with regarding a serum study being conducted insofar as it has academic interest, but RRP ISA opposes any attempt to frame this so-called “first study” as a “gateway study” which could lead to further studies if and only if the data profile on RRP patients turns out to be low.
My objections are as follows: (1) I know from previous research with the AIDS community that while anal and genital HPV are opportunistic infections, RRP is as rare in persons living with AIDS as it is in people with fully intact serum immune systems. (2) This suggest that the determinative variable that either prevents or facilitates expression of RRP is to be found at the local mucosa, not in the serum immune system. (3) Since serum immune levels appear not to be a relevant factor in determining who gets RRP, why should we hold RRP patients to any “if and only if” standard in testing their blood? There is no logic for making further testing of Gardasil’s effect in any way contingent on this serum immune level at baseline. (4) To further complicate matters, most adults who have been exposed to genital HPV will almost certainly test positive for HPV antibodies, whether or not they ever had RRP. One couldn’t possibly use adults as patients in the test group, since their sexual histories would get in the way and introduce another independent variable. You would have to use children to obtain a sexually naïve group of subjects. This last issue wildly skews the data. The testing of serum immune markers in children may be interesting, but I believe that it is inappropriate to hold further testing of Gardasil hostage to the data.
What we really need to know NOW is how well Gardasil works on adults and children who have RRP. In this, serum testing before and after taking Gardasil makes perfect sense. Here, we can test for neutralizing antibody levels and compare the subject group with that of people without RRP. Granted, this is for early onset HPV, but still, doesn’t Merck want to know whether Gardasil even generates an immunological response in RRP patients? If yes, it might want to make the Gardasil available without cost to those researchers who want to test it NOW, not in 2-3 years.
This brings us to my third point, which is to introduce a specific research initiative for consideration. I have already discussed this with Merck. RRP ISA’s share of this research funding for 2007-8 can be as high as $100,000. Merck, it should be said, also has much deeper pockets than we do. It may chose to actually help fund the RFP that RRP ISA will be proposing to run in Lancet, Laryngoscope and Annals of Otolaryngology. It can also provide the Gardasil free of charge. In sharing this third point with you, I am providing a heads-up regarding the upcoming RFP.
I won’t attempt to go into the science or detail in this prepared statement, but VLP vaccines like Gardasil have led to some interesting clinical responses to HPV in animals. Gardasil has been thoroughly tested in the reproductive tract, and I believe Merck when it says that Gardasil cannot be used to treat pre-existing disease of the cervix. But does that also include the respiratory tract? Not even Merck can answer authoritatively on this and, in fact, the man often attributed to be inventor of Gardasil, Dr. Ian Fraser of Australia, is moving into phase 2 clinical testing of a VLP RRP vaccine that he says is very much like Gardasil but without the same adjuvant.
My point here is that there is a lot we don’t know about Gardasil, and even more importantly, we don’t know about its behavior with HPV disease of the respiratory tract or in the head and neck regions. Even if Gardasil can’t generate a massive enough cytotoxic assault on chronic head/neck/respiratory HPV disease, might not the massively heightened immunological effects of antibody levels somehow, in ways we don’t yet fully understand, also “turn on” the local immune system so patients might finally see HPV as an enemy against which to mount an assault? Could it not help, to use a rather hackneyed metaphor, “to turn on the light?”
I am an adult patient who has had RRP for over 30 years. My surgical need ranged from 4 a year to once very year and a half. I’m the kind of guy that still maintains a conservative stance when it comes to the use of cidofovir. I am naturally skeptical about any “new” therapy that’s been bandied around the family advocate online bulletin boards. I try and put anecdote in perspective whenever it pops up on RRP ISA’s online board.
Anyway, in March of last year, I began experimenting with artemisinin, as researched by Dr. Richard Schlegel and others on his team at Georgetown. Dr. Schlegel, who has a Bill and Melinda Gates to study HPV and who himself holds both a PhD and a MD, wrote very compellingly of research using artemisinin in dogs who had been inoculated with the canine variant of RRP. The artemisinin appears to resolve the canine infections. It is a unique cytotoxic agent in that it is selectively absorbed in cancer cells and cells infected with HPV. Other journal articles have also been published on artemisinin, not the least from the University of Washington. The drug is used all over the Far East to treat malaria. A few days ago, I heard from a South Korean otolaryngologist wishing to use it to treat RRP.
I have a hunch here that the two together may be greater than the sum of their parts. I’ve used artemisinin for over a year and I finished my three Gardasil shots last January. It may be an unrelated coincidence, but my voice has never been better in the 30 years I’ve had RRP.
RRP ISA is proposing to bear the lion’s share in funding a medical/scientific study to research the effect of using Gardasil and artemisinin-like substance on RRP. The PIs could use a crossover design testing Gardasil alone, artemisinin alone, and also the two together.
Thank you for your kind attention. I would be happy to correspond further with any and all. I can provide bibliographic references if asked. My hope is to put a proposal package in May. I would love to hear from you if you are interested in discussing this proposal further!
Michael Green, MSW, LICSW
President and Executive Director
International RRP ISA Center
RRP Task Force Meeting Friday, April 27, 2007
Manchester Grand Hyatt Hotel, Madeline A
San Diego, California
Members in Attendance:
Craig Derkay, MD Chair
Farrel Buchinsky, MD
Andy Inglis, MD
Fred Kozak, MD
Paolo Campisi, MD
Sukgi Choi, MD
Patrick Froehlich, MD
John Schweinforth, MD
Marc Thorne, MD
Clark Rosen, MD
Michael Haupert, MD
Bob and Susan Spock
Marshall Smith, MD
Dorothy Wiley, PhD
Seth Pransky, MD
Chris Hartnick, MD
Chuck Myer, MD
Bruce Maddern, MD
Dr. Derkay called the meeting to order at around 7am apologizing for the early hour. The members introduced themselves around the table.
The minutes from the Toronto Task Force meeting were approved without revision after having been previously distributed by email.
1. Old business: As discussed in Toronto, the Task Force was invited by the AAO-HNS to once again prepare a presentation on Sunday night of the Academy meeting in Washington DC on RRP and the HPV vaccine supported by an educational grant from Merck. The Dessert Symposium in Toronto was very well received with an overflowing audience. This year, Dr. Buchinsky, representing both the Task Force and the AAOHNS’ Infectious Disease committee, will moderate a panel consisting of Drs. Derkay and Wiatrak from the RRP Task Force, Dr. Eliav Barr and Dr. Bob Ferris. The presentation will again follow the President’s Reception and promises to be more interactive with a focus on what Otolaryngologists need to know about HPV disease.
2. Old business: As previously discussed in Toronto, LA and Chicago, an article has been submitted to the Archives for their Clinical Controversies section regarding the role of Cidofovir in the treatment of RRP. It continues to go through the Peer Review process.
Update on HPV vaccine related events/issues
1. Dr. Derkay and Dr. Pransky have been working with intermediates to prepare informative slides regarding RRP and the HPV vaccine for non-otolaryngologists lecturing around the country on the benefits of the HPV vaccine.
2. Dr. Derkay is assisting Merck in the design of a study to estimate the worldwide burden of RRP. The protocol being considered will attempt to estimate the current incidence of the disease in several geographically distinct regions in the US, Canada and Europe. It is hoped that this data will then serve as a baseline for measuring the effect of the vaccine in the future.
3. Dr. Buchinsky is organizing a multi-institutional (and patient initiated) analysis of anti-HPV titer levels in current RRP patients. Merck is considering funding this initiative and offering technical support for performing the ELISA assays. There are some regulatory (IRB) challenges as well as some logistical challenges to overcome (specimens need to be shipped on dry ice after the serum is separated). Task Force members should expect to hear more about this and ways for their patients to become enrolled later this summer. Dr Patrick Froehlich from Lyon, France is working with Dr. Peter Bull from the UK through the European RRP Task Force to achieve a similar investigation. The RRP Task Force will endeavor to merge the missions and protocols to try and get the most usable data out of the two studies. It was noted that in Europe, the pharmaceutical company with the license for the vaccine is Sanofi-Pasteur.
4. Richard Haupt, MD from Merck was unable to attend due to a prior commitment but has communicated Merck’s continued desire to support RRP research.
1. Dr. Derkay reported on the acquisition of Stressgen by Nventa and the declaration by the CEO to continue to pursue a Phase III study of HspE7.
2. Mark Shikowitz at LIJ is currently enrolling adults (and will shortly anticipate to begin enrolling children) in a clinical trial of the Cox 2 inhibitor Celebrex. Initial results have been promising.
3. Dr, Buchinsky gave an update to the group regarding his ongoing NIH study attempting to identify genes responsible for RRP susceptibility. To date, he has accumulated about 250 patient sets (pairs or triads) and has two candidate genes under investigation. He continues to recruit additional families. Please notify him of your desire to participate in this study.
4. Paolo Campisi reported on his efforts to organize a Canadian registry of RRP patients.
5. Dr. Froehlich reported on his efforts to coordinate with BAPO to form a European Working Group to study epidemiological characteristics of RRP and to work with Sanofi on a European HPV/RRP study similar to that being developed in the US.
6. Michael Green, representing the RRP ISA, submitted a prepared statement for the group regarding his views on Gardasil and other RRP treatment initiatives such as Artemisinin.
7. Bob and Susan Spock, representing the RRPF, submitted a prepared statement from their group supporting efforts to work with Merck to investigate the benefits of the quadrivalent vaccine as a therapy for RRP.
Updated statement on the role of HPV typing
1. Discussion ensued regarding the potential benefits of recommending that all RRP patients be subtyped (as 6, 11 or 6/11). The recent literature was discussed as well as the anecdotal experiences of the practitioners around the table.
2. In lieu of the anticipated introduction of a commercially available assay by Roche later this year, it was agreed that the Task Force will hold off on making a recommendation regarding this issue until the test is more readily accessible.
1. The RRPF is planning an RRP Focus Session to be held in Washington, DC on Saturday September 15, 2007 from 1pm-5pm. Anyone with specific presentation interests or questions should contact Bill Stern at email@example.com.
2. The next meeting of the RRP Task Force will take place at the AAO-HNS meeting in Washington, DC. The most likely dates are Sunday September 16 in the late afternoon or Monday morning September 17. I will pass along the specifics once the rooms and times are assigned.
There being no further business (or time), the meeting was adjourned shortly after 8am.
RRP Task Force Meeting Monday September 18, 2006
Royal York Hotel, New Brunswick Room
Members in attendance:
Craig Derkay, MD Chair
Dave Tunkel, MD
John McClay, MD
Jerry Thompson, MD
Farrel Buchinsky, MD
Robert Ruben, MD
Patrick Froehlich, MD
Seth Pransky, MD
Fred Kozak, MD
Paolo Campisi, MD
Clark Rosen, MD
Andy Inglis, MD
Scott Manning, MD
Steve Conley, MD
Nancy Bauman, MD
Chantal Giguere, MD
The meeting was called to order by Dr. Derkay at around 5pm. Chocolate was distributed to all members (in case they did not receive any on Sunday night).
The minutes from May’s meeting in Chicago were approved without revision.
1. Old business: As discussed in Chicago, the Task Force was invited by the AAO-HNSF to prepare a presentation on Sunday night at the Academy meeting on RRP and the HPV vaccine to be supported by an educational grant by Merck. This was scheduled to follow the President’s Reception and was to be termed a “Dessert Reception”. The speakers and topics included: Brian Wiatrak (moderator), Andy Inglis (introduction to RRP), Seth Pransky (update on medical management), Clark Rosen (update on surgical management) and Craig Derkay (update on the HPV vaccine). Somewhat to our surprise, the entire room filled up (around 400 people) and an additional 200-300 people were turned away. Needless to say, all of the chocolate was consumed. The Academy has already approached us regarding the possibility of doing this again next year in DC.
2. Old business: As previously discussed in LA and Chicago, an article was drafted for the Archives Clinical Controversies section regarding the role of Cidofovir in the treatment of RRP. It is currently going through the peer review process.
Update on HPV vaccine efforts.
1. Dr. Derkay attended the Sci-Med vaccine meeting in NYC to update the slide packet regarding RRP and Head and Neck cancer and the potential benefits of an HPV vaccine.
2. Drs. Campisi and Rosen attended the Merck investigators meeting in July to discuss research initiatives with the Merck scientists (Eliav Barr). The feedback was generally negative regarding the possibilities of Merck funding a wide-scale clinical trial regarding utilizing the vaccine as a therapeutic agent. Dr. Derkay has scheduled a conference call with the Merck executives for Wednesday September 27, 2007 to further discuss this issue.
3. Dr. Froehlich participated in a meeting with Aventis/Pasteur (they own the European rights to Gardasil) at the international HPV meeting in Prague and left with a much more optimistic impression of the possibilities of organizing a surveillance/epidemiology study of the therapeutic and preventative benefits of the vaccine. Dr. Bennett Lee from France is poised to take the lead in organizing this.
The Task Force discussed the relative benefits of accepting an unrestricted educational grant from Merck vs. seeking out funding from other organizations in order to carry out a study to obtain pilot data. Thoughts raised included use of the vaccine intra-lesionally in a cohort of “active” RRP patients; using the vaccine IM in a cohort of quiescent patients and using the vaccine in patients with disease outside the larynx. Also discussed was the potential for using it in pregnant patients (probably not feasible in the US) and in newborns at-risk for acquiring the disease. The consensus was to try and do something in a coordinated fashion so that useful data could be obtained. Dr. Derkay pledged to keep the group informed after his conference call with Merck to decide on the next step.
1. HsPE7: Phase III trial is currently on hold. NVenta has purchased Stressgen and is still tentatively planning a trial but this is most likely up to 2 years in the future.
2. Celebrex study at LIJ: Currently enrolling patients only at LIJ but awaiting potential funding from NIH to expand to 6 sites. Preliminary results encouraging.
3. RRP gene identification: Dr. Buchinsky has continued to recruit centers and has expanded the pool of patients by reaching out to the patient/parent groups. He has 4 candidate genes that he is investigating. He is applying for an RO1 grant to allow him to perform a genome-wide scan on the specimens. Three preliminary publications have already been generated from the research effort.
4. Topical agents: ICTV (a topical agent showing promise in the treatment of plantar warts) is being formulated for potential use with RRP.
5. Combination of PDL and surgery: Dr. Hartnick from Mass E&E has engaged Pentax in discussions of funding a multi-center investigation of the benefits of the pulse dye laser in children when used in conjunction with surgical resection.
6. Canadian Registry: Dr. Campisi is working with his Canadian colleagues to create a registry of RRP patients. The group discussed case definitions for inclusion in the registry. Similar registries are also being contemplated in the UK and in Sweden.
Updated statement on Viral typing:
Drs. Buchinsky, Wiatrak, Conley, Campisi and Pransky are working on formulating a Task Force statement regarding the need/role for HPV typing in RRP patients. They are engaged in a meta-analysis of the literature and hope to time the statement in coordination with the anticipated commercial launch of an assay by Roche.
The meeting was adjourned at 6pm. The next meeting of the Task Force is planned for San Diego, CA in conjunction with the COSM/ASPO meeting in late April.
RRP TASK FORCE MEETING MINUTES Tuesday September 27, 2005
La Brea Room, Westin Hotel
Los Angeles, CA
TASK FORCE MEMBERS IN ATTENDANCE:
Dr. Craig S. Derkay
Dr. Sukgi Choi
Dr. Seth Pransky
Dr. Andy Inglis
Dr. Farrel Buchinsky
Dr. Paolo Campisi
Dr. Marshall Smith
Dr. Brian Wiatrak
Dr. George Zalzal
Dr. Paul Willging
Dr. Chuck Bower
Dr. Stephen Conley
Angie Duggins, RN
Dr. Derkay called the meeting to order at 5:15pm. The members of the Task Force present introduced themselves to each other and the minutes from the May meeting were approved.
1. The group discussed the Cidofovir for RRP Reassessment of Risks Statement. Dr. Derkay discussed that this will be published in an edited format in the Bulletin and in the International Journal of Pediatric Otolaryngology. At the suggestion of the group, it will also be featured as a “Clinical Controversies” section of Archives this winter. Michael Green also offered to post it on the RRP ISA website.
1. Update on HPV vaccine efforts. Dr. Derkay discussed the Merck and GSK vaccine efforts. The quadrivalent Merck vaccine is likely to be the first to be addressed by FDA. Discussion ensued regarding advocacy efforts to assure that the Red Book committee and ACIP understand the importance to the RRP community of including HPV 6 and 11 in the vaccine. The group felt that education of our colleagues would be important as a first step and scientific presentations are planned for SENTAC in December and ASPO in May. A formal advocacy effort will wait licensing of the vaccine and will revolve around making recommendations regarding the target groups and the preferred product.
2. RRPF / International RRP ISA Focus group summary
Michael Green summarized the talks given at Saturday’s RRP Focus group meeting. These included discussions regarding current research into RRP (HspE7, Celebrex, Genetic susceptibility) and related HPV topics (Hamlet, Artemisinine) as well as reviews of the literature and personal anecdotes. Attendance was very good and discussions lively. The group expressed hope that the Focus group would continue to meet along side AAOHNS and COSM meetings.
3. Research initiatives
a. HspE7—the hope is that this phase III clinical trial will launch before the spring and will recruit up to 150 children from 30-35 sites. A PI meeting is anticipated for January/February.
b. Celebrex—study has been launched in adults with RRP with LIJ as main center (5-6 other centers planned). 2-year crossover design. Lower dose of Celebrex to allay fears with cardiac toxicity.
c. RRP gene identification—Dr. Buchinsky updated the group on his progress. Specimens from 82 subjects have been analyzed. A dedicated IRB consultant has made a big difference and may be the key to opening up several more centers’ patients.
d. Aldera and other topical agents—limited use at the present time.
e. Canadian registry—Dr. Campisi reported on the progress he is making in unifying the data in Canada and establishing a patient registry. They have started with their patients at Toronto Sick Kids and have data on 75 children over 10 years.
f. HPV vaccine effects—Keerti Shah from Johns Hopkins has planned a prospective surveillance of new cases to monitor the effectiveness of the new HPV vaccine in prevention of RRP.
4. Statement on Viral Typing
In lieu of several new publications on the topic, the group has asked Dr. Wiatrak to perform a meta-analysis regarding the value of HPV typing and report back to the Task Force in May. If indicated, the group may issue new guidelines this summer regarding the value of subtyping.
The group discussed “where to go from here” as a Task Force. With the advent of the HPV vaccines on the horizon there may be an opportunity to put RRP more in the forefront and to leverage additional research funds. Discussion ensued regarding whether we should form our own society, establish a “study group”, meet independent of ASPO and/or AAOHNS, involve the HPV research community and other disciplines, interact more/less with the patient groups or keep doing business as we have been. Drs. Derkay and Pransky agreed to formulate some options for the group and communicate these prior to the spring meeting.
6. Future meetings
The group will strive to meet in Chicago over the weekend of May 21-22, 2006 in conjunction with ASPO.
There being no further business and the hour getting late, the meeting was adjourned at 630pm.
The International RRP ISA Center is a member of the RRP Task Force and expects to attend the September 2003 meeting in Florida. The following is a summary of the May 3, 2003 meeting, which we did not attend.
Meeting format: The meeting was preceded by an RRP symposium sponsored by Stressgen regarding a possible Phase III trial for the HSP-E7 RRP drug. An ASPO [American Society of Pediatric Otolaryngology] Fellowship Directors followed.
CDC funding issue: A letter was distributed that was addressed to Dr. Julie Gerberding, Director of CDC, regarding the future of the Task Force. Our understanding is that the RRP Task Force is still unfunded despite hundreds of petitions, letters and advocacy to senators, etc. For more, click here.
Grant acceptance announcement: It was announced that Dr. Farrell Buchinsky's K08 NIH Grant to evaluate for genetic susceptibility in RRP was accepted and funded.
HspE7: The potential for a phase III investigation of a heat-shock protein linked to HPV that has shown efficacy in patients with ano-genital warts was also brought up; many Task Force sites may be recruited to provide patients.
Merck vaccine and RRP: The Task Force has made contact with the Merck investigators who have developed an HPV 6/11 vaccine; this was done with the intent of placing RRP on the investigators' radar screen.
ASPO survey results: The web-based ASPO member survey on RRP management, mortality and experience with adjuvant modalities was presented and discussed. At the Task Force’s request, this study also looked at RRP mortality (26 reported cases) and causes of death (progressive respiratory failure followed by anesthesia-related causes and malignant transformation). Microdebrider removal has now replaced the use of the CO2 laser as the most frequent tool, and spontaneous respiration has replaced the laser-safe ETT as the dominant means of providing anesthesia management. Cidofovir is presently the most common adjuvant agent utilized (34/35 practices using an adjuvant therapy) with experiences reported on 72 patients. Results with Cidofovir were generally favorable (about 2/3rds) though most rated it a 2-4 on a grading scale of 1-5 (5 being “a miracle drug”).
The Task Force expects to reconvene at the AAO-HNS meeting in Orlando over September 21-24, 2003.