Gossypol Acetic Acid in Treating Patients With Recurrent, Metastatic, or Primary Adrenocortical Cancer That Cannot Be Removed By Surgery
Condition: Recurrent Adrenocortical Carcinoma; Stage III Adrenocortical Carcinoma; Stage IV Adrenocortical Carcinoma
MeSH terms: Carcinoma; Adrenocortical Carcinoma
Intervention: R-(-)-gossypol acetic acid
Intervention description: 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.
Intervention MeSH terms: Acetic Acid; Retinol acetate; Gossypol acetic acid; Gossypol
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 29.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      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.
    

Eligibility criteria:

        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