ODAC Rejects IntraDose for Head and Neck Cancer

BETHESDA, Maryland—The FDA’s Oncologic Drugs Advisory Committee (ODAC) has voted not to recommend that the agency approve IntraDose (injectable cisplatin/epinephrine gel, Matrix Pharmaceuticals). Matrix is seeking to market the drug for the treatment of recurrent or refractory squamous cell carcinoma of the head and neck in patients not considered curable with surgery or radiotherapy.

IntraDose is a gel formulation that is injected directly into tumors to deliver high concentrations of cisplatin (Platinol) for an extended period of time. In addition to head and neck cancers, it is in clinical trials as a treatment for primary hepatic carcinoma and colorectal cancer.

FDA may approve a drug for marketing under either what is commonly known as regular approval or accelerated approval. Both require an agent to meet the same standards of safety and efficacy. Accelerated approval, however, requires the sponsor to carry out a phase IV post-marketing study to further confirm a drug’s efficacy. In bringing drugs before ODAC, companies specify under which of the categories they seek approval.

Matrix sought regular approval for IntraDose, but in response to a question from the panel, company officials indicated they would accept accelerated approval.

After hearing and discussing presentations by the company and a FDA medical review team, the committee unanimously voted against recommending regular approval for IntraDose. Then, at the request of panel member Scott D. Lippman, MD, professor of medicine and cancer prevention, M.D. Anderson Cancer Center, the panel voted on whether to recommend IntraDose for accelerated approval. That vote failed 9 to 3, with one abstention.

Matrix presented two double-blinded studies with identical designs of Intra-Dose vs placebo in which a total of 178 patients were randomized 2 to 1 in favor of the active agent.

In the two studies, the company reported a combined overall response rate of 29% for the IntraDose arm—19% complete response and 10% partial response—compared with a 2% complete response rate and no partial responders in patients receiving the placebo gel.

However, the FDA product review team and ODAC members raised a number of issues critical of the two studies. They questioned, for example, the design, whether the two trials were adequately blinded, the number of dosing errors that occurred throughout their duration, and the number of patients terminated due to disease progression.

These issues led the FDA and ODAC members to question whether the study results adequately demonstrated a true clinical benefit for patients. "FDA found there was a reasonable rate of local tumor response, but little evidence of clinical benefit," said medical team leader Grant Williams, MD.

Matrix officials indicated after the committee vote that they would continue their research of IntraDose for the treatment of head and neck cancer, and would return late to seek FDA approval of the drug.