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Gossypol, Cisplatin, and Etoposide in Treating Patients With Advanced Solid Tumors or Extensive Stage Small Cell Lung Cancer
This study is currently recruiting participants.
Verified by National Cancer Institute (NCI), April 2008
First Received: October 13, 2007   Last Updated: January 21, 2009   History of Changes
Sponsors and Collaborators: University of Wisconsin, Madison
National Cancer Institute (NCI)
Information provided by: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00544596
  Purpose

RATIONALE: Gossypol 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 gossypol together with combination chemotherapy may help kill more tumor cells.

PURPOSE: This phase I trial is studying the side effects and best dose of gossypol when given together with cisplatin and etoposide in treating patients with advanced solid tumors or extensive stage small cell lung cancer.


Condition Intervention Phase
Lung Cancer
Unspecified Adult Solid Tumor, Protocol Specific
Drug: R-(-)-gossypol acetic acid
Drug: cisplatin
Drug: etoposide
Phase I

MedlinePlus related topics: Cancer Lung Cancer
Drug Information available for: Acetic acid Cisplatin Etoposide Etoposide phosphate
U.S. FDA Resources
Study Type: Interventional
Study Design: Treatment
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

Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Toxicity and tolerability [ Designated as safety issue: Yes ]
  • 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 [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Pharmacokinetics [ Designated as safety issue: No ]

Estimated Enrollment: 34
Study Start Date: September 2007
Estimated Primary Completion Date: November 2008 (Final data collection date for primary outcome measure)
Detailed Description:

OBJECTIVES:

Primary

  • 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).
  • 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.
  • To evaluate the antitumor activity of this combination per tumor measurements using the RECIST criteria.

Secondary

  • To evaluate the pharmacokinetics of R-(-)-gossypol as a single agent and in combination with cisplatin and etoposide in plasma.
  • 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.

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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

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)

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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00544596

Locations
United States, Wisconsin
University of Wisconsin Paul P. Carbone Comprehensive Cancer Center Recruiting
Madison, Wisconsin, United States, 53792-6164
Contact: Clinical Trials Office - University of Wisconsin Paul P. Carbo     608-262-5223        
Sponsors and Collaborators
University of Wisconsin, Madison
Investigators
Principal Investigator: George Wilding, MD University of Wisconsin, Madison
  More Information

Additional Information:
No publications provided

Study ID Numbers: CDR0000570006, WCCC-CO-07901
Study First Received: October 13, 2007
Last Updated: January 21, 2009
ClinicalTrials.gov Identifier: NCT00544596     History of Changes
Health Authority: Unspecified

Keywords provided by National Cancer Institute (NCI):
unspecified adult solid tumor, protocol specific
extensive stage small cell lung cancer

Study placed in the following topic categories:
Thoracic Neoplasms
Carcinoma, Neuroendocrine
Contraceptive Agents
Contraceptive Agents, Female
Contraceptive Agents, Male
Gossypol acetic acid
Etoposide phosphate
Gossypol
Carcinoma
Neuroendocrine Tumors
Carcinoma, Small Cell
Neuroectodermal Tumors
Radiation-Sensitizing Agents
Cisplatin
Respiratory Tract Diseases
Lung Neoplasms
Lung Diseases
Neoplasms, Germ Cell and Embryonal
Retinol acetate
Neuroepithelioma
Adenocarcinoma
Antineoplastic Agents, Phytogenic
Etoposide
Neoplasms, Glandular and Epithelial

Additional relevant MeSH terms:
Thoracic Neoplasms
Carcinoma, Neuroendocrine
Contraceptive Agents
Antineoplastic Agents
Physiological Effects of Drugs
Neoplasms, Nerve Tissue
Contraceptive Agents, Female
Reproductive Control Agents
Contraceptive Agents, Male
Etoposide phosphate
Gossypol
Neoplasms by Site
Respiratory Tract Diseases
Cisplatin
Lung Neoplasms
Neoplasms, Germ Cell and Embryonal
Therapeutic Uses
Antispermatogenic Agents
Etoposide
Respiratory Tract Neoplasms
Neoplasms by Histologic Type
Gossypol acetic acid
Pharmacologic Actions
Neuroendocrine Tumors
Carcinoma
Carcinoma, Small Cell
Neuroectodermal Tumors
Neoplasms
Radiation-Sensitizing Agents
Lung Diseases

ClinicalTrials.gov processed this record on May 06, 2009