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

National Cancer Institute (NCI)

Status and phase: Completed; Phase 2

Conditions: Stage IV Adrenocortical Carcinoma; Recurrent Adrenocortical Carcinoma; Stage III Adrenocortical Carcinoma

Treatments: Drug: R-(-)-gossypol acetic acid

Study type: Interventional

Funder types: NIH

Identifiers

NCT00848016

N01CM00038 (U.S. NIH Grant/Contract)

NCI-2009-01160

CDR0000635024

MC0771

N01CM00070 (U.S. NIH Grant/Contract)

8035

Details and patient eligibility

About

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.

Full description

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.

Enrollment: 29 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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29 participants in 1 patient group

Treatment (R-(-)-gossypol acetic acid)

Experimental group

Description:

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.

Treatment:

Drug: R-(-)-gossypol acetic acid