A Phase II Study of AT-101 in Recurrent Extensive Stage Small Cell Lung Cancer
I. To determine the objective response rate of R-(-)-gossypol in patients with recurrent
chemotherapy-sensitive extensive stage small cell lung cancer.
I. To determine the time to disease progression. II. To determine the overall survival. III.
To assess the toxicities associated with this drug. IV. To explore whether intratumoral
Bcl-2 family member expression correlates with sensitivity to targeting by R-(-)-gossypol.
V. To explore whether the administration of R-(-)-gossypol causes specific induction of the
intrinsic apoptotic pathway.
OUTLINE: This is a multicenter study.
Patients receive oral R-(-)-gossypol once daily on days 1-21. Courses repeat every 28 days
in the absence of disease progression or unacceptable toxicity.
Blood is collected periodically during treatment for pharmacodynamic analysis. Peripheral
blood mononuclear cells are analyzed via protein isolation and western blotting for Bcl-2,
cytoplasmic release of cytochrome c, and caspase activation. Available tumor tissue blocks
are assessed by immunohistochemistry.
After completion of study therapy, patients are followed periodically for up to 5 years.
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Number of Participants With Confirmed Tumor Response Defined to be Either a Complete Response (CR) or Partial Response (PR)
The number of successes will be estimated by counting the number of participants with confirmed responses. A confirmed tumor response is defined to be either a CR or PR noted as the objective status on 2 consecutive evaluations at least 4 weeks apart. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions: A Complete Response (CR) requires the disappearance of all target lesions A Partial Response (PR) requires a >=30% decrease in the sum of the longest diameter of target lesions from baseline measurements.
During the first 6 courses of treatment
United States: Food and Drug Administration
|Mayo Clinic||Rochester, Minnesota 55905|
|University of Pittsburgh Cancer Institute||Pittsburgh, Pennsylvania 15213|