Trials of drugs to treat cancer in the central nervous system (CNS) that has metastasized from solid tumors outside the CNS should examine whether the treatment controls the cancer at all disease sites, according to an FDA draft guidance released last week.

Because metastatic cancer is a systemic disease, the guidance says, it is not enough to assess a drug by its ability to shrink tumors in the CNS alone. The guidance offers recommendations for the design of trials of systemic anticancer drugs that include patients with CNS metastases as well as trials conducted exclusively in patients with CNS metastases.

Efficacy claims based on endpoints measuring CNS activity alone “may not be appropriate,” and the same goes for labeling indications, the agency says, adding that the effectiveness of investigational cancer drugs depends on “whether the cancer is controlled at all disease sites.”

The FDA recommends that clinical trial designs for drugs to treat such cancers include case report forms that ask for information on all prior CNS-directed treatments patients may have received; that the protocol specify a gap of at least 12 weeks, generally, between patients’ completion of CNS radiation therapy and study entry; and that the protocol specify appropriate stratification factors for randomization to minimize bias based on prior treatments the patients may have undergone.

Study endpoints could include time-to-event, overall survival, tumor assessment, capture duration of response and time from prior radiation therapy.

Comments on the draft guidance are due Oct. 26.

Read the draft guidance here: https://bit.ly/2QxgYGz.