Clinical trial NCT00848016: Gossypol Acetic Acid in Treating Patients With Recurrent, Metastatic, or Primary Adrenocortical Cancer That Cannot Be Removed By Surgery
Official title: A Phase II Study of the Orally Administered Negative Enantiomer of Gossypol (AT-101) in Patients With Advanced Adrenocortical Carcinoma (ACC)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Recurrent Adrenocortical Carcinoma
Stage III Adrenocortical Carcinoma
Stage IV Adrenocortical Carcinoma
Lead sponsor: National Cancer Institute (NCI)
Sponsor class: NIH
First posted: 2009-02-20
Enrollment: 29
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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.

Detailed 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.

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

Primary outcomes:
measure: 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
timeFrame: Up to 2 years
Secondary outcomes:
measure: Overall Survival
timeFrame: From registration to date of last follow-up or death due to any cause, assessed up to 2 years
measure: Progression-free Survival
timeFrame: From registration to progression or death, whichever occurs first, up to 2 years.
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: University of Southern California
state: California
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
Study officials:
affiliation: Mayo Clinic
name: Michael Menefee
role: PRINCIPAL_INVESTIGATOR
References: