Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outcomes
Outline
Trial Contact Information
Registry Information

Alternate Title

Gossypol, Cisplatin, and Etoposide in Treating Patients With Advanced Solid Tumors or Extensive Stage Small Cell Lung Cancer

Basic Trial Information

Phase	Type	Status	Age	Sponsor	Protocol IDs
Phase I	Treatment	Active	18 and over	NCI	WCCC-CO-07901 8062, CO 07901, NCT00544596

Objectives

Primary

1. To determine the maximum tolerated dose or recommended phase II dose of 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).
2. To evaluate the toxicity and tolerability of R-(-)-gossypol in combination with cisplatin and etoposide in patients with advanced, refractory solid tumors and/or ES-SCLC.
3. To evaluate the antitumor activity of this combination per tumor measurements using the RECIST criteria.

Secondary

1. To evaluate the pharmacokinetics of R-(-)-gossypol as a single agent and in combination with cisplatin and etoposide in plasma.
2. To perform pharmacodynamic studies (i.e., genotyping of drug metabolizing enzymes, gene expression, and proteomics of drug-related pathways) on archived blood samples from patients treated with R-gossypol in combination with cisplatin and etoposide.

Entry Criteria

Disease Characteristics:

• Diagnosis of 1 of the following:
  • Histologically confirmed malignancy that is metastatic or unresectable and for which standard curative or palliative measures do not exist or are no longer effective (dose-escalation cohorts)
  • Histologically or cytologically confirmed extensive stage small cell lung cancer (ES-SCLC) (maximum tolerated dose expansion cohort)
• Patients with small cell lung carcinoma and brain metastases should have stable/improved lesions for at least 1 month following treatment, no neurological symptoms, and no requirement for corticosteroids
  • Prior whole-brain radiotherapy for brain metastases allowed for patients with small cell lung carcinoma

Prior/Concurrent Therapy:

Inclusion criteria

• See Disease Characteristics
• Recovered from prior therapy
• At least 4 weeks since prior chemotherapy (6 weeks for nitrosoureas and mitomycin C)
• At least 4 weeks since prior radiotherapy
• More than 4 weeks since prior and no other concurrent investigational agents
• Concurrent routine use of erythropoietin allowed at investigator's discretion

Exclusion criteria

• Prior therapy that inhibits the Bcl-2 family
• Prior chemotherapy or radiotherapy in patients with ES-SCLC
• Prior use of R-(-)-gossypol
• Requirement for routine or prophylactic use of hematopoietic growth factors (including granulocyte colony stimulating factor, granulocyte macrophage colony stimulating factor, or interleukin-11)
• Concurrent combination antiretroviral therapy for HIV-positive patients

Patient Characteristics:

Inclusion criteria

• ECOG performance status (PS) 0-2 (Karnofsky PS 60-100%)
• Life expectancy > 12 weeks
• Leukocytes ≥ 3,000/mcL
• Absolute neutrophil count ≥ 1,500/mcL (no transfusions allowed)
• Platelets ≥ 100,000/mcL (no transfusions allowed)
• Total bilirubin < 1.5 mg/dL
• AST(SGOT)/ALT(SGPT) ≤ 2.5 X institutional upper limit of normal
• Serum creatinine < 1.5 X institutional upper limit of normal OR creatinine clearance ≥ 45 mL/min
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception during and for at least 1 month after completion of study treatment

Exclusion criteria

• History of allergic reactions attributed to compounds of similar chemical or biologic composition to L-gossypol or other agents used in study
• Any condition (e.g., gastrointestinal tract disease resulting in an inability to take oral medication or a requirement for IV alimentation, prior surgical procedures affecting absorption, or active peptic ulcer disease) that impairs ability to swallow and retain R-(-)-gossypol tablets
• Patients with malabsorption syndrome, disease significantly affecting gastrointestinal function, or resection of the stomach or small bowel
• Patients with ulcerative colitis, inflammatory bowel disease, or a partial or complete small bowel obstruction
• Uncontrolled intercurrent illness including, but not limited to, any of the following:
  • Ongoing or active infection
  • Symptomatic congestive heart failure
  • Unstable angina pectoris
  • Cardiac arrhythmia
• Psychiatric illness or social situations that would limit compliance with study requirements
• Patients with > grade 2 symptomatic hypercalcemia (based on investigator discretion)

Expected Enrollment

Outcomes

Toxicity and tolerability
Response (complete and partial response, stable disease, or progressive disease; early death from systemic progression, CNS progression, or both; early death from toxicity, early death because of other cause, or unknown) as assessed by RECIST criteria

Pharmacokinetics

Outline

This is a dose-escalation study of R-(-)-gossypol.

Patients receive oral R-(-)-gossypol twice daily on days 1-3, cisplatin 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.]

Trial Contact Information

Trial Lead Organizations

University of Wisconsin Paul P. Carbone Comprehensive Cancer Center

George Wilding, MD, Principal investigator		Ph: 608-263-8610; 800-622-8922 Email: gxw@medicine.wisc.edu

U.S.A.
Wisconsin
	Madison
	University of Wisconsin Paul P. Carbone Comprehensive Cancer Center
		Clinical Trials Office - University of Wisconsin Paul P. Carbone Comprehensive Cancer Center	Ph:  608-262-5223

Registry Information
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
Trial Start Date		2007-09-11
Trial Completion Date		2008-11-04 (estimated)
Registered in ClinicalTrials.gov		NCT00544596
Date Submitted to PDQ		2007-09-11
Information Last Verified		2009-07-05
NCI Grant/Contract Number		CA62491

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