Experimental Cancer Drug Access To Be Topic Of FDA Consensus Conference

FDA is planning a consensus conference to discuss issues surrounding single-patient INDs and expanded access programs for unapproved oncology agents, Oncologic Drug Products Division Medical Team Leader Grant Williams, MD, told FDA's Oncologic Drugs Advisory Committee June 7.

Questions FDA would like to discuss at the conference, Williams said, include: "When should a company provide access to experimental treatment? And how should the drug be distributed so the patients are treated fairly?"

"We believe that FDA and the National Cancer Institute can play an important role in facilitating this dialogue," Williams said. One possibility would be to work with the American Society of Clinical Oncology for the conference.

FDA would like to help manufacturers and the patient community agree on a set of norms about when expanded access is appropriate.

Compassionate use programs are among the topics to be discussed during an FDA meeting, "A Conversation About Cancer Drug Development With Cancer Patient Advocates," scheduled for June 29. The meeting, which will also address fast-track designation, quality of life issues and the Patient Consultant Program, will be held at the Westin Fairfax Hotel in Washington, D.C. beginning at 2 p.m.

The June 7 discussion, which focused on single-patient use of investigational cancer drugs, was a continuation of a December meeting (¹ (Also see "Experimental Cancer Drug Use Increased By Trial "Hype" - FDA Cmte. Guest" - Pink Sheet, 18 Dec, 2000.)). FDA is seeking input as it refines its criteria for evaluating requests for compassionate use INDs.

The committee suggested that inequities in access to unapproved cancer drugs should be addressed as a part of an overall reform of the clinical trial process.

Unequal access to Treatment INDs and expanded access programs reflects a larger problem - that patients are poorly informed about ongoing clinical trials, the panel told FDA.

The FDA Modernization Act of 1997 included a provision designed to increase access to information about trials via a National Institutes of Health's data bank, "ClinicalTrials.gov." FDA issued a draft guidance a year ago with recommendations for IND sponsors submitting trial information to the database. (² (Also see "Mandatory Trial Reporting To Be Required For Nearly Half Of IND Protocols" - Pink Sheet, 3 Apr, 2000.)).

FDA will make "another guidance document available very shortly that will tell sponsors how to get their trials into ClinicalTrials.gov," Office of Special Health Issues Associate Commissioner Theresa Toigo said.

FDA currently asks that companies list expanded access programs for cancer drugs in the National Cancer Institute's Physician Data Query database.

However, industry "compliance with PDQ in general has been very poor," FDA's Cancer Liaison Program Public Health Specialist Patricia Delaney said. With about "1,850 clinical trials in the database, the number of industry-sponsored trials...was 200 and it's now going down."

FDA should "encourage [industry] to be proactive and think about a planned access program as part of their drug development process, especially if the sponsor is planning a big media campaign in advance of drug approval," committee member Douglas Blayney, MD, Wilshire Oncology Medical Group, said.

During the December meeting, AstraZeneca VP-Medical Oncology Gerard Kennealey, MD, asked FDA to address how data from expanded access protocols might be used by the agency when it evaluates the NDA for that agent.

"The most important data to collect are clearly those on adverse reactions, especially serious events and unexpected toxicity," FDA's Williams said. "Other data are probably seldom very useful in this setting."

Expanded access protocols may be able to answer some limited questions, Williams said. "What we might consider doing is some more simple randomized studies in this setting, comparing two doses of investigational drug...and evaluate very simple safety or efficacy endpoints such as survival."

"Some forms of expanded access could actually be done in the form of large, simple trials," Office of Drug Evaluation I Director Robert Temple, MD, agreed.

Temple will testify June 20 at a House Government Reform committee hearing on providing access to experimental drugs to terminally ill patients.

The committee was asked to consider standard clinical scenarios and assess when single-patient treatment with an unapproved oncology drug might be appropriate.

Committee Chair Stacy Nerenstone, MD, Hartford Hospital, summarized the committee view that "pretty much under no circumstance would I say a Phase I drug should be given out for a single-patient IND."

A majority of the committee said that when no standard therapy exists, access to a Phase II oncologic agent should be allowed on a case-by-case basis. Nerenstone described Phase II as a "gray area," emphasizing that the "likelihood that this patient is going to benefit is indeed quite small."

Toxicity will remain a concern with an early Phase II agent, the committee said. AstraZeneca Senior Medical Director-Oncology Steven Averbuch, MD, suggested. "It is only going to be at the end of Phase II where we begin to have a level of confidence about that risk" and can "begin to make judgments about expanded access."

Temple observed that the committee's comments were "entirely consistent with the rules for Treatment IND" currently in place at FDA, which suggest "there has to be reasonable evidence of effectiveness."

In a scenario where available treatment shows a marginal survival benefit, the committee emphasized the importance of patient education. The consensus of the panel was that a Phase II agent could be permitted in that case.

When standard therapy is available that provides a substantial prolongation of median survival, the committee agreed FDA should not permit single-patient treatment with an investigational new drug, regardless of its phase of development.

Oncology Drug Products Division Director Richard Pazdur, MD, told the committee that "the vast majority" of patients seeking a single-patient IND are ineligible for enrollment in clinical trials for the drug because they are receiving too many therapies.

"If the majority of patients fit this category, then maybe the clinical study should have a stratification that defines that subgroup," committee member Victor Santana, MD, University of Tennessee, suggested.