A Phase 1 Study of R-(-)-Gossypol (AT-101) in Combination With Cisplatin and Etoposide in Patients With Advanced Solid Tumors and Extensive-Stage Small Cell Lung Cancer
I. To determine the maximum tolerated dose (MTD) or recommended phase II dose (RP2D) of
AT-101 (R-(-)-gossypol) when combined with cisplatin and etoposide in patients with
advanced, refractory solid tumors and/or extensive stage small cell lung cancer (ES-SCLC).
In addition, to determine the MTD or RP2D of AT-101 when combined with cisplatin, etoposide,
II. To evaluate the toxicity and tolerability of AT-101 in combination with cisplatin and
etoposide in patients with advanced, refractory solid tumors and/or ES-SCLC. In addition,
evaluate the toxicity and tolerability of AT-101 with cisplatin, etoposide, and Neulasta.
III. To evaluate the antitumor activity of this combination per tumor measurements using the
Response Evaluation Criteria In Solid Tumors (RECIST) criteria.
I. To evaluate the pharmacokinetics of AT-101 as a single agent and in combination with
cisplatin and etoposide in plasma.
II. To perform pharmacodynamic studies (genotyping of drug metabolizing enzymes, gene
expression, and proteomics of drug-related pathways) on archived blood samples from patients
treated with AT-101 in combination with cisplatin and etoposide.
OUTLINE: This is a dose-escalation study of R-(-)-gossypol.
Patients receive oral R-(-)-gossypol twice daily on days 1-3, cisplatin intravenously (IV)
over 60 minutes on day 1*, and etoposide IV over 30 minutes on days 1*-3. Treatment repeats
every 21 days for up to 6 courses during the dose escalation and 4 courses in the expanded
extensive stage small cell lung cancer cohort, in the absence of disease progression or
Blood samples are collected on day 1 of courses 1 and 2 for pharmacokinetic analysis,
biomarker assays, and correlative studies.
After completion of study treatment, patients are followed for 30 days.
[Note: *Cisplatin and etoposide will be started on day 2 during course 1; they will be given
on day 1 during all subsequent courses.]
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Toxicity and tolerability of R-(-)-gossypol acetic acid in combination with cisplatin and etoposide in terms of types and severities by the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 3.0
The 95% confidence interval will be obtained.
Assessed up to 30 days after completion of study treatment
University of Wisconsin Hospital and Clinics
United States: Food and Drug Administration
|University of Wisconsin Hospital and Clinics||Madison, Wisconsin 53792-0001|
|Sanford Cancer Center-Oncology Clinic||Sioux Falls, South Dakota 57104|
|UW Health Oncology - 1 South Park||Madison, Wisconsin 53715|
|Gundersen Lutheran||La Crosse, Wisconsin 54601|