Gossypol Acetic Acid in Treating Patients With Recurrent, Metastatic, or Primary Adrenocortical Cancer That Cannot Be Removed By Surgery

Study Overview
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Brief Summary
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This phase II trial is studying how well gossypol acetic acid works in treating patients with recurrent, metastatic, or primary adrenocortical cancer that cannot be removed by surgery. Drugs used in chemotherapy such as 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.

Detailed Description
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PRIMARY OBJECTIVE: I. To determine the proportion of patients with recurrent, metastatic, or primary unresectable adrenocortical carcinoma who achieve an objective response to R-(-)-gossypol acetic acid. SECONDARY OBJECTIVES:: I. To evaluate the safety of this drug in these patients. II. To determine the progression-free and overall survival of these patients. OUTLINE: This is a multicenter study. Patients receive oral R-(-)-gossypol acetic acid once daily on days 1-21. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up every 3 months for up to 2 years.

Official Title
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A Phase II Study of the Orally Administered Negative Enantiomer of Gossypol (AT-101) in Patients With Advanced Adrenocortical Carcinoma (ACC)

Conditions
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Recurrent Adrenocortical Carcinoma, Stage III Adrenocortical Carcinoma, Stage IV Adrenocortical Carcinoma

Intervention / Treatment
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* Drug: R-(-)-gossypol acetic acid


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically or cytologically confirmed adrenocortical carcinoma Recurrent, metastatic, or primary unresectable disease Measurable disease, defined as ≥ 1 lesion accurately measured in ≥ 1 dimension as ≥ 2.0 cm by conventional techniques or ≥ 1.0 cm by spiral CT scan No adrenocortical tumors that, in the Principal Investigator's opinion, are potentially resectable by surgical excision alone No symptomatic or progressive brain metastases Patients with treated brain metastases ≥ 6 months prior to study who are clinically and radiographically stable or improved and are off steroids are eligible Must undergo an MRI of the brain or CT scan of the head with contrast ≤ 4 weeks prior to study Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-2 or Karnofsky PS 60-100% Life expectancy ≥ 12 weeks White blood cell count (WBC) ≥ 3,000/mm3 Absolute neutrophil count (ANC) ≥ 1,500/mm3 Platelet count ≥ 100,000/mm3 Total bilirubin < 1.5 mg/dL Aspartate aminotransferase (AST) and Alanine aminotransferase (ALT) ≤ 2.5 times upper limit of normal Serum creatinine ≤ 1.7 mg/dL or creatinine clearance ≥ 40 mL/min Able to take oral medications on a regular basis Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception prior to, during, and for ≥ 1 month after completion of study treatment No HIV positivity No 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 situation that would limit compliance with study requirements No condition or disease that significantly affects gastrointestinal (GI) function or impairs the ability to swallow and retain oral medications including, but not limited to, any of the following: GI tract disease or a requirement for IV alimentation Prior resection of the stomach or small bowel or surgical procedures affecting absorption Active peptic ulcer disease Malabsorption syndrome Ulcerative colitis Inflammatory bowel disease Partial or complete small bowel obstruction No other malignancy within the past 2 years except nonmelanoma skin cancer or in situ cervical cancer No symptomatic hypercalcemia > grade 2 No history of allergic reactions attributed to compounds of similar chemical or biological composition to R-(-)-gossypol acetic acid Fully recovered from prior surgical procedures and recovered to ≤ grade 1 from adverse events due to previous treatments No prior racemic gossypol or R-(-)-gossypol acetic acid More than 4 weeks since prior chemotherapy, biologic therapy, major surgery, or radiotherapy (≥ 6 weeks for carmustine or mitomycin C) Prior and concurrent mitotane and ketoconazole allowed for patients with hormonal excess More than 4 weeks since prior and no concurrent treatment with another investigational agent No concurrent prophylactic use of hematopoietic growth factors (e.g., filgrastim [G-CSF], sargramostim [GM-CSF], interleukin-11) during the first course of study treatment Not requiring routine use of platelet transfusions to maintain ANC or platelet count above required thresholds Exclusion Criteria: No concurrent combination antiretroviral therapy for HIV-positive patients

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment (R-(-)-gossypol acetic acid)<br>Patients receive 20mg oral R-(-)-gossypol acetic acid once daily on days 1-21. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity. | Drug: R-(-)-gossypol acetic acid<br>* Participants take 20mg oral R-(-)-gossypol acetic acid once daily on days 1-21. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity.<br>* Other names: AT-101;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The Proportion of Patients Who Achieve a Confirmed Objective Response to Treatment, Either Partial Response (PR) or Complete Response (CR) as Defined by Response Evaluation Criteria In Solid Tumors (RECIST) Criteria | In order for a patient to be a confirmed objective responder, they must achieve a PR or CR on consecutive evaluations, at least 4 weeks apart. The proportion of patients who achieve a confirmed objective response to treatment will be estimated by the standard binomial estimator, i.e., the number of successes divided by the total number of evaluable patients. Complete Response (CR): Disappearance of all target lesions and normalization of tumor biomarkers. Partial Response (PR): At least a 30% decrease in the sum of the longest dimension (LD) of target lesions taking as reference the baseline sum LD. | Up to 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival | The overall survival time is defined as the time from registration to date of last follow-up or death due to any cause. Estimated using the method of Kaplan-Meier. | From registration to date of last follow-up or death due to any cause, assessed up to 2 years | 
| Progression-free Survival | The progression-free survival is defined as the time from registration to the date of progression or death, whichever comes first. The distributions of progression-free survival time will be estimated using the method of Kaplan-Meier. | From registration to progression or death, whichever occurs first, up to 2 years. |