R-(-)-Gossypol Acetic Acid, Cisplatin, and Etoposide in Treating Patients With Advanced Solid Tumors or Extensive Stage Small Cell Lung Cancer

Unspecified Adult Solid Tumor, Protocol Specific Clinical Trial

Official title: 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

Status Completed

Clinical Trial Summary

This phase I trial is studying the side effects and best dose of R-(-)-gossypol acetic acid when given together with cisplatin and etoposide in treating patients with advanced solid tumors or extensive stage small cell lung cancer. R-(-)-gossypol acetic acid may stop the growth of cancer by blocking blood flow to the tumor. Drugs used in chemotherapy, such as cisplatin and etoposide, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving R-(-)-gossypol acetic acid together with combination chemotherapy may help kill more tumor cells.

Clinical Trial Description

PRIMARY OBJECTIVES:

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, and Neulasta.

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.

SECONDARY OBJECTIVES:

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 unacceptable toxicity.

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.] ;

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Extensive Stage Small Cell Lung Cancer
• Lung Neoplasms
• Small Cell Lung Carcinoma
• Unspecified Adult Solid Tumor, Protocol Specific

• NCT number: NCT00544596
• Study type: Interventional
• Source: National Cancer Institute (NCI)
• Status: Completed
• Phase: Phase 1
• Start date: September 2007