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

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.

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