BETHESDA, MarylandThe 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
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
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 arm19% complete response and 10% partial responsecompared
with a 2% complete response rate and no partial responders in patients
receiving the placebo gel.