Clinical Trials in Patients with Resected Stage IIB and III Melanoma

1
Clinical Trials in Patients with Resected Stage
IIB and III Melanoma

• Craig L. Slingluff, Jr., M.D.
• Professor of Surgery, University of Virginia
• Director, Human Immune Therapy Center, UVA
• Co-chair, Melanoma Committee, ECOG
• Vice-chair, Melanoma Committee, ACOSOG
• NIH funded investigator on multiple
  investigator-initiated clinical trials. R01
  CA57653, R01 CA78519, R21 89937

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UVA-Mel39

• A synthetic peptide vaccine trial in patients
  with stage IIB-III melanoma was proposed (IND
  9847) for patients who refuse IFN or are not
  candidates for IFN
• The FDA ruling
• patients who simply refuse IFN are not
  candidates.
• patients who have refused IFN and who are 6
  months or more after definitive surgery are no
  longer considered to be IFN candidates.
• Thus, patients who refuse IFN can enter this
  trial once 6 months have elapsed.

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Risk of opening trials to those who refuse IFN

• The only salient argument for legislating
  against the freedom of patients to decide to
  enter a clinical trial after refusal of an
  approved therapy is that patients may be exposed
  to risk of obtaining inadequate information about
  the standard therapy because of real or perceived
  bias on the part of some clinical investigators.
   

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The process of informed consent

• However, the process of informed consent for
  clinical trial entry is based on the belief that
  patients can be informed adequately to consent to
  clinical studies that may have unknown benefit
  and known or unknown risks.
• To argue that informed consent cannot provide
  adequate protection of patients who choose not to
  take an approved therapy, is tantamount to
  arguing that informed consent cannot provide
  adequate protection of patients in any setting.

5
Proposal for phase II trials in patients eligible
for HD-IFN?.

• A tenable policy for design of phase II
  clinical trials in patients who may be eligible
  for an FDA-approved therapy should assure patient
  protection while also ensuring freedom of
  self-determination by patients. My suggestion is
  thatpatients eligible for a standard therapy
  should be required to study and to document
  understanding of an FDA-approved document
  detailing the risks and benefits of the
  FDA-approved therapy.

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Benefits of system for informed consent

• Ensure that no patient who is eligible for an
  FDA-approved therapy would refuse that therapy
  and enter a clinical trial without receiving
  acceptable information about the standard
  therapy.
• Lead to more uniform information dissemination
  about the standard therapy than is currently
  provided to patients who refuse that therapy.
• Permit patients the freedom to choose the
  management they find most consistent with their
  priorities (survival and quality of life).
• Increase the proportion of patients whose therapy
  is regulated and monitored by the FDA, thereby
  improving patient safety generally.

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Alternate recommendation Shorten wait after
refusal of IFN

• If the FDA develops a policy that it will not
  allow any patients to enter phase II clinical
  trials who are candidates for an FDA-approved
  therapy, then it is requested that this policy be
  applied strictly, based on the conditions in
  which the drug was originally tested.
• The clinical trials of HD-IFN have restricted
  entry to patients treated within 56 days of
  definitive surgical therapy. More recent trials
  permit entry up to almost 3 months after
  definitive therapy.
• There are no conclusive data addressing the
  therapeutic value of HD-IFN administered more
  than 3 months after definitive therapy.
• Thus, it is requested that the FDA allow entry of
  patients onto experimental phase II trials 3
  months after definitive therapy (rather than 6
  months). 

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Summary

• Patients have the right to refuse any or all
  standard therapy, for any disease, because of
  their personal goals related to quality of life
  issues, toxicity, or other perceptions of the
  effects of that therapy.
• Patients who choose not to take an approved
  therapy, after adequate information is provided,
  should not be excluded from trials that other
  patients with the same stage disease are allowed
  to enter. This can be accomplished with informed
  consent.
• To disallow that freedom interferes with patient
  rights and also is harmful to investigation of
  new therapies, which are sorely needed for
  melanoma and for most cancers.