A Study of Combination Chemotherapy and Surgical Resection in the Treatment of Adrenocortical Carcinoma: Continuous Infusion Doxorubicin, Vincristine and Etoposide With Daily Mitotane Before and After Surgical Resection

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00001339
Recruitment Status : Completed
First Posted : November 4, 1999
Last Update Posted : March 4, 2008
Information provided by:
National Institutes of Health Clinical Center (CC)

Brief Summary:

Patients who have no response to preoperative chemotherapy and no residual disease following surgery on Regimen A are treated on Regimen B postoperatively.

The following acronyms are used:

DDD Mitotane, NSC-38721

DOX Doxorubicin, NSC-123127

VCR Vincristine, NSC-67574

VP-16 Etoposide, NSC-141540

Regimen A: 4-Drug Combination Chemotherapy followed by Surgery followed by 4-Drug Combination Chemotherapy. DDD/DOX/VCR/VP-16; followed by surgical debulking; followed by DDD/DOX/VCR/VP-16.

Regimen B: Single-Agent Chemotherapy. DDD.

Condition or disease Intervention/treatment Phase
Adrenal Cortical Carcinoma Drug: doxorubicin, vincristine, and etoposide with mitotane Phase 2

Detailed Description:
This is a study of infusional doxorubicin, vincristine, and etoposide in combination with daily oral mitotane in patients with adrenocortical cancer. Although mitotane has been used extensively in adrenocortical cancer and has documented single agent activity, only limited experience is available in the use of mitotane in combination with chemotherapy. In this trial the primary reason for using mitotane is an attempt to enhance therapeutic efficacy, based on its documented in-vitro activity as an antagonist of P-glycoprotein. The goal of this study is to determine the efficacy of this therapy by treating patients who are considered candidates for surgical resection at presentation or following a response to therapy. Following chemotherapy, patients deemed surgical candidates can undergo surgical resection with evaluation of response. Patients responding to chemotherapy will resume the combination treatment after surgery. Patients who do not respond will be maintained on single agent mitotane until it is deemed ineffective.

Study Type : Interventional  (Clinical Trial)
Enrollment : 42 participants
Primary Purpose: Treatment
Official Title: A Study of Combination Chemotherapy and Surgical Resection in the Treatment of Adrenocortical Carcinoma: Continuous Infusion Doxorubicin, Vincristine and Etoposide With Daily Mitotane Before and After Surgical Resection
Study Start Date : August 1993
Study Completion Date : August 2002

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Ages Eligible for Study:   Child, Adult, Older Adult
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Biopsy-proven primary or recurrent adrenocortical carcinoma considered surgically resectable at presentation or potentially resectable following an initial response to chemotherapy.

Potentially resectable disease includes primary lesion, nodal metastases, and liver and lung metastases if limited in size and number.

Patients for whom surgical resection is considered unlikely may be entered at the discretion of the investigator.

Measurable disease at presentation required.

A life expectancy of at least 3 months and a performance status (Karnofsky scale) of 70 percent or greater.

Prior chemotherapy is allowed, however, the patient should not have received chemotherapy four weeks before presentation.

Patients who have received prior doxorubicin may be enrolled provided they meet all other entry criteria and have an ejection fraction greater than 40 percent determined by MUGA scan.

Prior mitotane therapy is allowed. A dose of 3 gm/day should have been tolerated for at least one week. Patients do not need to be off mitotane therapy prior to starting this protocol.

WBC greater 3,000/mm(3); Platelet count greater than 100,000/mm(3); Creatinine clearance greater than 50 ml/min; bilirubin less than 1.5 mg/dl; serum transaminase less than 2 times normal.

Patient should be a good surgical candidate.

Must sign an informed consent and be geographically accessible to return for follow up treatment.

No presence of a second malignancy, other than squamous cell carcinoma of the skin.

No active systemic infection.

Must not be currently receiving treatment which cannot be discontinued with the following agents: diltiazem, nicardipine, phenothiazines, phenytoin, terfenadine or verapamil.

No positive serology for HIV.

No positive pregnancy test.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00001339

United States, Maryland
National Cancer Institute (NCI)
Bethesda, Maryland, United States, 20892
Sponsors and Collaborators
National Cancer Institute (NCI)

Publications: Identifier: NCT00001339     History of Changes
Other Study ID Numbers: 930200
First Posted: November 4, 1999    Key Record Dates
Last Update Posted: March 4, 2008
Last Verified: August 2002

Keywords provided by National Institutes of Health Clinical Center (CC):
Multidrug Resistance
Reversal of Drug Resistance

Additional relevant MeSH terms:
Adrenocortical Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Adrenal Cortex Neoplasms
Adrenal Gland Neoplasms
Endocrine Gland Neoplasms
Neoplasms by Site
Adrenal Cortex Diseases
Adrenal Gland Diseases
Endocrine System Diseases
Liposomal doxorubicin
Etoposide phosphate
Antibiotics, Antineoplastic
Antineoplastic Agents
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents, Phytogenic
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Antineoplastic Agents, Hormonal