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

Purpose

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

Condition	Intervention	Phase
Recurrent Adrenocortical Carcinoma Stage III Adrenocortical Carcinoma Stage IV Adrenocortical Carcinoma	Drug: R-(-)-gossypol acetic acid	Phase 2

Study Type:	Interventional
Study Design:	Endpoint Classification: Efficacy Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	A Phase II Study of the Orally Administered Negative Enantiomer of Gossypol (AT-101) in Patients With Advanced Adrenocortical Carcinoma (ACC)

Resource links provided by NLM:

MedlinePlus related topics: Cancer

Drug Information available for: Acetic acid, glacial

U.S. FDA Resources

Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:

The proportion of patients who achieve a confirmed objective response to treatment, either partial response (PR) or complete response (PR) as defined by Response Evaluation Criteria In Solid Tumors (RECIST) criteria [ Time Frame: Up to 2 years ] [ Designated as safety issue: No ]
Patient evaluability [ Time Frame: Up to 2 years ] [ Designated as safety issue: No ]
All patients meeting the eligibility criteria who have signed a consent form and begun treatment will be considered evaluable for response.
Response probability defined as the proportion of patients who achieve a confirmed objective response [ Time Frame: Up to 2 years ] [ Designated as safety issue: No ]
Estimated by the standard binomial estimator; the number of successes divided by the total number of evaluable patients and 90% Duffy-Santer confidence intervals that take into account the multi-stage nature of this design.

Secondary Outcome Measures:

Toxicity defined as adverse events that are classified as either possibly, probably, or definitely related to study treatment, graded using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 [ Time Frame: Up to 2 years ] [ Designated as safety issue: Yes ]
The maximum grade for each type of toxicity will be recorded for each patient, and frequency tables will be reviewed to determine toxicity patterns.
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 ]
Estimated using the method of Kaplan-Meier.
Time to progression [ Time Frame: From registration to the date of progression or last follow-up, whichever comes first, assessed up to 2 years ] [ Designated as safety issue: No ]
Estimated using the method of Kaplan-Meier.
Progression-free rate [ Time Frame: 6 months ] [ Designated as safety issue: No ]
Evaluated using the 6-month rates and associated confidence intervals.
Time to treatment failure [ Time Frame: From registration to the date the patient discontinues treatment, assessed up to 2 years ] [ Designated as safety issue: No ]
Estimated using the method of Kaplan-Meier.
Time to subsequent therapy [ Time Frame: Up to 2 years ] [ Designated as safety issue: No ]
Evaluated using the method of Kaplan-Meier.
Duration of response [ Time Frame: From the date of documentation of response (PR or CR) until the date of progression or last follow-up (whichever comes first) in the subset of patients with confirmed response, assessed up to 2 years ] [ Designated as safety issue: No ]

Enrollment:	44
Study Start Date:	February 2009
Primary Completion Date:	March 2012 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Treatment (R-(-)-gossypol acetic acid) 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.	Drug: R-(-)-gossypol acetic acid Given orally Other Name: AT-101

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

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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
ECOG performance status (PS) 0-2 or Karnofsky PS 60-100%
Life expectancy ≥ 12 weeks
WBC ≥ 3,000/mm3
ANC ≥ 1,500/mm3
Platelet count ≥ 100,000/mm3
Total bilirubin < 1.5 mg/dL
AST and 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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00848016

Locations

United States, California
University of Southern California
Los Angeles, California, United States, 90033-0804
United States, Minnesota
Mayo Clinic
Rochester, Minnesota, United States, 55905

Sponsors and Collaborators

National Cancer Institute (NCI)

Investigators

Principal Investigator:

Michael Menefee

Mayo Clinic

More Information

No publications provided

Responsible Party:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00848016 History of Changes
Other Study ID Numbers:	NCI-2009-01160, MC0771, N01CM00070, N01CM00038, CDR0000635024
Study First Received:	February 19, 2009
Last Updated:	December 21, 2012
Health Authority:	United States: Food and Drug Administration

Additional relevant MeSH terms:

Carcinoma
Adrenocortical Carcinoma
Adrenal Cortex Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Adenocarcinoma
Adrenal Gland Neoplasms
Endocrine Gland Neoplasms
Neoplasms by Site
Adrenal Cortex Diseases
Adrenal Gland Diseases
Endocrine System Diseases
Retinol acetate
Gossypol acetic acid

Gossypol
Adjuvants, Immunologic
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Anticarcinogenic Agents
Protective Agents
Antineoplastic Agents
Therapeutic Uses
Contraceptive Agents, Male
Contraceptive Agents
Reproductive Control Agents
Antineoplastic Agents, Phytogenic
Contraceptive Agents, Female
Spermatocidal Agents

ClinicalTrials.gov processed this record on May 22, 2013