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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00848016
First received: February 19, 2009
Last updated: April 17, 2014
Last verified: January 2014

February 19, 2009
April 17, 2014
February 2009
March 2012   (final data collection date for primary outcome 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 [ Time Frame: Up to 2 years ] [ Designated as safety issue: No ]

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.

Proportion of patients who achieve a confirmed objective response (complete or partial response by RECIST criteria) to treatment [ Designated as safety issue: No ]
Complete list of historical versions of study NCT00848016 on ClinicalTrials.gov Archive Site
  • Overall Survival [ Time Frame: From registration to date of last follow-up or death due to any cause, assessed up to 2 years ] [ Designated as safety issue: No ]
    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.
  • Progression-free Survival [ Time Frame: From registration to progression or death, whichever occurs first, up to 2 years. ] [ Designated as safety issue: No ]
    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.
  • Toxicity as assessed by NCI CTCAE v3.0 [ Designated as safety issue: Yes ]
  • Time to progression and overall survival [ Designated as safety issue: No ]
  • Time to treatment failure and time to subsequent therapy [ Designated as safety issue: No ]
  • Duration of response [ Designated as safety issue: No ]
Not Provided
Not Provided
 
Gossypol Acetic Acid in Treating Patients With Recurrent, Metastatic, or Primary Adrenocortical Cancer That Cannot Be Removed By Surgery
A Phase II Study of the Orally Administered Negative Enantiomer of Gossypol (AT-101) in Patients With Advanced Adrenocortical Carcinoma (ACC)

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.

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.

Interventional
Phase 2
Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
  • Recurrent Adrenocortical Carcinoma
  • Stage III Adrenocortical Carcinoma
  • Stage IV Adrenocortical Carcinoma
Drug: R-(-)-gossypol acetic acid
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.
Other Name: AT-101
Experimental: Treatment (R-(-)-gossypol acetic acid)
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.
Intervention: Drug: R-(-)-gossypol acetic acid
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
29
June 2012
March 2012   (final data collection date for primary outcome measure)

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
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT00848016
NCI-2009-01160, MC0771, 8035, CDR0000635024, N01CM00070, N01CM00038
Not Provided
National Cancer Institute (NCI)
National Cancer Institute (NCI)
Not Provided
Principal Investigator: Michael Menefee Mayo Clinic
National Cancer Institute (NCI)
January 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP