Non-Protocol Access to Experimental Agents

NCI provides experimental anti-cancer agents for children and adults with cancer primarily through clinical trials sponsored by the Cancer Therapy Evaluation Program (CTEP). Only well-designed clinical trials can reliably determine whether promising experimental anti-cancer agents actually help persons with cancer.

Outside of clinical trials, there are several mechanisms by which CTEP/NCI makes experimental agents available when there is substantial clinical evidence that the agents may provide benefit for persons with particular types of cancer. The two primary CTEP/NCI mechanisms for non-protocol access to experimental agents are the Special Exception process, and Treatment Referral Center Protocols. These programs are briefly summarized below, with links provided to the CTEP Investigator's Handbook, which provides further information about each program.

The ability of CTEP/NCI to provide non-protocol access for a specific investigational agent through one of these mechanisms depends upon several factors, in addition to evidence that the agent actually provides benefit for persons with specific types of cancer. Have standard therapies been exhausted for this patient? Is the patient ineligible or unable to be treated on a research protocol? There must be a sufficient supply of the agent for ongoing and planned clinical trials. The agent must be able to be given safely outside of a clinical trial environment. Also, if the agent is being co-developed by CTEP and a pharmaceutical company, the pharmaceutical collaborator must agree to provide the agent for this use.

The Special Exception process (similar to Single-Patient INDs through the FDA) is the most broadly applicable procedure for obtaining non-protocol access to experimental agents. Through the Special Exception process, CTEP/NCI makes experimental agents available when there is objective clinical evidence that the agent is active against the cancer for which the request is being made. Considerable evidence must attest to the activity of the agent for the requested indication, and reports of low response rates, or responses of brief duration, or anecdotal reports of an occasional response are not sufficient to justify approval. The Special Exception process may also be used to provide an experimental agent to someone who has previously received the agent in a clinical trial and has shown benefit from the agent, but who no longer is able to receive the agent through the clinical trial.

Examples of experimental agents that have been provided to children and adults with cancer over the past decade through our Special Exception procedures include topotecan (neuroblastoma), all-trans retinoic acid (acute promyelocytic leukemia), arsenic trioxide (acute promyelocytic leukemia), fenretinide (neuroblastoma), and compound 506U78 (T-cell acute lymphoblastic leukemia). The CTEP Investigator's Handbook (Section 18) describes the Special Exception process in more detail and provides procedures for receiving agents by Special Exception.

The other mechanism by which CTEP/NCI provides access to experimental agents is through Treatment Referral Center (TRC) Protocols. TRC Protocols are prepared for certain high priority diseases when NCI identifies a patient population for which it is felt an investigational agent should be made available. CTEP/NCI provides a TRC Protocol to Cancer Centers, which can then choose to use the TRC Protocol as a treatment option. The first TRC Protocol was developed by CTEP/NCI in 1991 to make paclitaxel available to patients with platinum refractory ovarian cancer who were not eligible for other clinical trials and who met criteria established to ensure patient safety. Further information about TRC Protocols is available in the CTEP Investigators' Handbook (Section 19)

27 January 2009