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A Phase II Study of AT-101 in Recurrent Extensive Stage Small Cell Lung Cancer

Phase 2
18 Years
Not Enrolling
Extensive Stage Small Cell Lung Cancer, Recurrent Small Cell Lung Cancer

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Trial Information

A Phase II Study of AT-101 in Recurrent Extensive Stage Small Cell Lung Cancer


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


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

V. 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.

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

- 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

- 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

- Ongoing or active infection

- Symptomatic congestive heart failure

- Unstable angina pectoris

- Cardiac arrhythmia

- Psychiatric illness or social situations that would limit compliance with study

- 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

- 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

Type of Study:


Study Design:

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

Outcome Measure:

Number of Participants With Confirmed Tumor Response Defined to be Either a Complete Response (CR) or Partial Response (PR)

Outcome Description:

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.

Outcome Time Frame:

During the first 6 courses of treatment

Safety Issue:


Principal Investigator

Maria Baggstrom

Investigator Role:

Principal Investigator

Investigator Affiliation:

Mayo Clinic


United States: Food and Drug Administration

Study ID:




Start Date:

November 2008

Completion Date:

October 2009

Related Keywords:

  • Extensive Stage Small Cell Lung Cancer
  • Recurrent Small Cell Lung Cancer
  • Lung Neoplasms
  • Small Cell Lung Carcinoma



Mayo ClinicRochester, Minnesota  55905
University of Pittsburgh Cancer InstitutePittsburgh, Pennsylvania  15213