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Fall 2005 Volume 6, Issue 6:
Making Clinical Trials More Patient-Friendly
By A Special Report by
The Unknown Patient
All new cancer drugs must be proven safe and effective in clinical trials before they can be made available to patients. At the 2005 IMF Support Group Leader Retreat, IMFer and leader of the Manhattan and White Plains (New York) myeloma support group
All new cancer drugs must be proven safe and effective in clinical trials before they can be made available to patients. At the 2005 IMF Support Group Leader Retreat, IMFer and leader of the Manhattan and White Plains (New York) myeloma support groups, Mike Katz, facilitated a focus group on patient concerns and preferences relative to clinical trials. Many issues previously Unknown to your reclusive author were discussed at this session and I thought it would be helpful to put some of them on paper.

Clinical trials are very important to patients. Without clinical trials, there could be no new drugs approved for the treatment of myeloma. When a promising new drug comes out of the laboratory, it must be tested in people via clinical trials. Clinical trials are conducted under very strict ethical standards, with many layers of scientific and regulatory review. As a result, they are very expensive and time-consuming to conduct. In recent years, patients have been brought more and more into the design process, which is very good news.

IMFer Mike Katz is co-chair of the Patient Representative Committee at the Eastern Cooperative Oncology Group (ECOG) and the liaison to ECOG's Myeloma Committee. This committee is co-chaired by Dr. Phillip Greipp (Mayo Clinic) and Dr. David Vesole (St. Vincent's Comprehensive Cancer Center).

ECOG has conducted many important cancer clinical trials. It is a cooperative group, funded by the National Cancer Institute (NCI), and its trials are available to patients via hundreds of participating treatment centers. ECOG's Myeloma Committee recently concluded a trial proving the safety and superiority of thalidomide and dexamethasone versus dexamethasone alone. This trial was cited in the "Approvable Letter" issued by the FDA in response to Celegene's submission of thalidomide. The FDA said that it expected to approve thalidomide after the results of this trial are submitted. The trial has already had a profound impact on patient care, with the thalidomide/dexamethasone combination all but replacing VAD (vincristine, Adriamycin, dexamethasone) as the standard front-line treatment for patients planning a stem cell transplant.

ECOG is currently conducting a trial testing the new agent Revlimid®. However, the Myeloma Committee designed this trial to go beyond the question of whether Revlimid is a safe and effective front-line treatment for myeloma. (Further information about this trial can be found at http://e4a03.myeloma.org.)The trial is asking two questions that are very important to patients:

  • If Revlimid does not work, will thalidomide work?

  • When given with Revlimid or thalidomide, will a lower dose of dexamethasone (40mg, given 1 day on, 7 days off) be as effective as the standard dose (40 mg, given 4 days on, 4 days off)?

This trial design received rave reviews at the 2004 IMF Support Group Leader Retreat. It was approved by the NCI in record time and is enrolling patients faster than original projections. It is an example of a "patient-friendly" trial in that it asks questions important to patients and is actually testing the efficacy of potentially less toxic treatments (Revlimid versus thalidomide, lower-dose versus standard-dose dexamethasone.) Traditionally, trials used "maximum tolerated doses" to maximize the possibility of a positive result for the treatment being tested, often in support of drug approval applications.

Having Mike Katz on the Myeloma Committee and having the Myeloma Committee participate in a focus group with the IMF Support Group Leaders clearly played a part in making this trial design more "patient-friendly." ECOG has been a pioneer in this area. Mike and his co-chair, Mary Lou Smith, sit on the ECOG Executive Committee, which reviews and approves all trial concepts.

At this year's IMF Support Group Leader Retreat, the Myeloma Committee once again participated in a focus group discussion with the attendees. The discussion first covered general issues that the support group leaders had with myeloma treatment and clinical trials, including:

  • Whether to have a stem cell transplant and the appropriate timing

  • If and when stem cells should be harvested if not having a transplant

  • Whether there are better therapies than stem cell transplants that patients would be forgoing by tracking into a front-line transplant program

  • What the alternatives to a stem cell transplant are

  • How to sort through all of the available combination therapies available today, both in terms of effectiveness of treatment as well as side effects/risks

  • General frustration with continued role of high-dose dexamethasone in so many treatment regimens and trials, given the side effects

  • Concerns about wasting time with drugs/treatments that don't work

  • Concerns that patients are being steered into clinical trials without being told what the alternative standard treatments would be

  • Feeling that the informed consent forms for clinical trials are too long and too hard to understand

  • Insurance coverage issues often influencing choice to enter clinical trial based on availability of free drug, leading more people with insurance issues to enroll

  • The need for more information on alternative/complimentary therapies, such as curcumin, particularly for MGUS and smoldering patient who have no imperative for standard treatment options but are looking to do something

  • The need for better pain management services

The next part of the discussion focused on clinical trials designs being considered by ECOG for the future. While confidentiality issues prevent discussion of the details of those designs, there were some general conclusions worth sharing:

  • In discussing potential trials for patients with Smoldering Myeloma, the group saw the following pros/cons but felt it was worth having trials available for patients who were anxious to do something beyond "watchful waiting":
    • Pros: Opportunity for a patient who feels like there's a "time bomb" in his/her body to participate in a trial that would allow one to do something to stop it from "exploding"

    • Cons:
      • Why should patients take a drug with possible side effects and risks when they are symptom free and feeling well?
      • Why should a patient risk developing a resistance to a medication that might be needed more urgently later on in the disease progression?

  • A number of concepts for front-line trials were discussed. The group strongly encouraged the Committee to consider designs that used newer, less toxic agents than thalidomide, the feeling being that patients need not be subjected to thalidomide's side-effects and risks if there were better alternatives available.

  • A concept for a consolidation therapy trial was discussed:
    • Consolidation therapy is given after the myeloma has been driven into remission by another therapy. For example, transplant is a consolidation therapy, as it is given after another therapy has driven the myeloma into remission.
    • The group was receptive to the trial concept, as they had been when an earlier version was discussed with them at the 2004 retreat. It was felt to be a good alternative for people who did not want do pursue transplant immediately after front-line therapy. People also liked the idea of having their stem cells harvested early in the process, as this was part of the trial design.
    • There was concern about the specification of double transplant as the salvage regimen (to be used if the patient relapsed after consolidation therapy). However, the Myeloma Committee representatives explained that the salvage regimen was not part of the trial protocol and did not necessarily have to be a tandem transplant or even an auto transplant.

The attendees felt empowered to be able to engage directly in the design process and the Myeloma Committee was grateful for their input. It does no one any good to go through the time and expense of opening clinical trials that are not attractive to patients.

The success of the Myeloma Committee Focus Group paved the way for a recommendation that annual patient focus groups be incorporated into the NCI's Blueprint for a Redesigned National Clinical Trials system. This recommendation was presented to the National Cancer Advisory Board and accepted for implementation. So, the myeloma community has once again led the way, setting an example for how to get things right in cancer treatment and research.

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