R-(-)-Gossypol Acetic Acid in Treating Patients With Recurrent Extensive-Stage Small Cell Lung Cancer

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00773955
First received: October 15, 2008
Last updated: April 23, 2014
Last verified: October 2011
  Purpose

This phase II trial is studying how well R-(-)-gossypol acetic acid works in treating patients with recurrent extensive-stage small cell lung cancer. Drugs used in chemotherapy, such as R-(-)-gossypol acetic acid, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing.


Condition Intervention Phase
Extensive Stage Small Cell Lung Cancer
Recurrent Small Cell Lung Cancer
Drug: R-(-)-gossypol acetic acid
Other: pharmacological study
Other: laboratory biomarker analysis
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase II Study of AT-101 in Recurrent Extensive Stage Small Cell Lung Cancer

Resource links provided by NLM:


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

Primary Outcome Measures:
  • Number of Participants With Confirmed Tumor Response Defined to be Either a Complete Response (CR) or Partial Response (PR) [ Time Frame: During the first 6 courses of treatment ] [ Designated as safety issue: No ]

    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.



Secondary Outcome Measures:
  • Survival Time [ Time Frame: From registration to death due to any cause, assessed up to 5 years ] [ Designated as safety issue: No ]
    Estimated using the method of Kaplan-Meier.

  • Time to Disease Progression [ Time Frame: From registration to the earliest date documentation of disease progression, assessed up to 5 years ] [ Designated as safety issue: No ]

    Time to disease progression is defined as the time from registration to the earliest date documentation of disease progression. Estimated using the method of Kaplan-Meier.

    Per the RECIST criteria, progression is defined as at least a 20% increase in the sum of Longest Dimension (LD) of target lesions taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions.


  • Duration of Response [ Time Frame: From the date at which the patient's earliest best objective status is first noted to be either a CR or PR to the earliest date progression is documented, assessed up to 5 years ] [ Designated as safety issue: No ]

Enrollment: 15
Study Start Date: November 2008
Study Completion Date: August 2010
Primary Completion Date: October 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment (R-(-)-gossypol)
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.
Drug: R-(-)-gossypol acetic acid
Given orally
Other Name: AT-101
Other: pharmacological study
Correlative studies
Other Name: pharmacological studies
Other: laboratory biomarker analysis
Correlative studies

Detailed Description:

PRIMARY OBJECTIVES:

I. To determine the objective response rate of R-(-)-gossypol in patients with recurrent chemotherapy-sensitive extensive stage small cell lung cancer.

II. To determine the time to disease progression. III. To determine the overall survival. IV. To assess the toxicities associated with this drug. V. To explore whether intratumoral Bcl-2 family member expression correlates with sensitivity to targeting by R-(-)-gossypol.

VI. 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.

  Eligibility

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

Inclusion Criteria:

  • Histologically or cytologically confirmed small cell lung cancer

    • Extensive stage disease
    • Recurrent disease
  • Measurable disease
  • Chemotherapy-sensitive disease, defined as:

    • No progression during first-line chemotherapy
    • No disease recurrence < 2 months after completion of first-line chemotherapy
  • Must have received prior platinum-based chemotherapy
  • No symptomatic or progressive brain metastases

    • Patients with previously treated brain metastases who are clinically and radiographically stable or improved and have been off steroids ≥ 14 days are eligible
  • ECOG performance status 0-2
  • Life expectancy > 12 weeks
  • Leukocytes ≥ 3,000/μL
  • ANC ≥ 1,500/μL
  • Platelet count ≥ 100,000/μL
  • Total bilirubin < 1.5 mg/dL
  • AST and ALT ≤ 2.5 times upper limit of normal
  • Serum creatinine ≤ 1.5 mg/dL OR creatinine clearance ≥ 60 mL/min
  • Hemoglobin > 8 g/dL
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception before, during, and for 30 days after completion of study therapy
  • Able to take oral medications on a regular basis
  • Willing to provide blood samples for mandatory correlative studies
  • No condition that impairs the ability to swallow and retain R-(-)-gossypol tablets, including the following:

    • Gastrointestinal tract disease resulting in an inability to take oral medication or a requirement for IV alimentation
    • Active peptic ulcer disease
  • No malabsorption syndrome or disease significantly affecting gastrointestinal function
  • No ulcerative colitis, inflammatory bowel disease, or a partial or complete small bowel obstruction
  • No uncontrolled concurrent 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
  • No symptomatic hypercalcemia > grade 2
  • No requirement for routine use of hematopoietic growth factors (including G-CSF, GM-CSF, or IL-11) or platelet transfusions to maintain ANC or platelet counts
  • No history of allergic reactions attributed to compounds of similar chemical or biologic composition to R-(-)-gossypol
  • No HIV positivity
  • Recovered from all prior therapy, including prior surgical procedures
  • No prior surgical procedures affecting absorption
  • No prior resection of the stomach or small bowel
  • No more than one prior chemotherapy regimen
  • No prior racemic gossypol or R-(-)-gossypol
  • At least 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin C)
  • At least 4 weeks since prior radiotherapy, hormonal agents, or biologic response modifiers
  • At least 4 weeks since prior and no concurrent investigational agents or devices
  • No concurrent prophylactic hematopoietic growth factors (including filgrastim [G-CSF], sargramostim [GM-CSF], or interleukin-11 [IL-11]) during course one
  • No concurrent combination antiretroviral therapy for HIV-positive patients
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00773955

Locations
United States, Minnesota
Mayo Clinic
Rochester, Minnesota, United States, 55905
Sponsors and Collaborators
Investigators
Principal Investigator: Maria Baggstrom Mayo Clinic
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00773955     History of Changes
Obsolete Identifiers: NCT01647113
Other Study ID Numbers: NCI-2009-01058, NCI-2009-01058, MAYO-MC0721, CDR0000616965, MC0721, 8027, N01CM62205, P30CA015083, N01CM62209
Study First Received: October 15, 2008
Results First Received: February 13, 2013
Last Updated: April 23, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Lung Neoplasms
Small Cell Lung Carcinoma
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
Carcinoma, Bronchogenic
Bronchial Neoplasms
Retinol acetate
Gossypol acetic acid
Gossypol
Adjuvants, Immunologic
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Anticarcinogenic Agents
Protective Agents
Antineoplastic Agents
Therapeutic Uses
Contraceptive Agents, Male
Contraceptive Agents
Reproductive Control Agents
Antineoplastic Agents, Phytogenic
Contraceptive Agents, Female
Spermatocidal Agents
Antispermatogenic Agents

ClinicalTrials.gov processed this record on August 19, 2014