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

NCT00001339 | Completed Phase 2

• 2 other identifiers: 93020093-C-0200
• Study Type: interventional
• Target: 42
• Locations: 1 country
• Sites: 1

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.

Conditions

Adrenal Cortical Carcinoma

Keywords

Multidrug Resistance; Reversal of Drug Resistance; P-Glycoprotein; MDR-1

Interventions

doxorubicin, vincristine, and etoposide with mitotane DRUG

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

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.

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (1)

National Cancer Institute (NCI)

Bethesda, Maryland, 20892, United States

Location

Related Publications (3)

• Luton JP, Cerdas S, Billaud L, Thomas G, Guilhaume B, Bertagna X, Laudat MH, Louvel A, Chapuis Y, Blondeau P, et al. Clinical features of adrenocortical carcinoma, prognostic factors, and the effect of mitotane therapy. N Engl J Med. 1990 Apr 26;322(17):1195-201. doi: 10.1056/NEJM199004263221705.

  PMID: 2325710 BACKGROUND

• Bates SE, Shieh CY, Mickley LA, Dichek HL, Gazdar A, Loriaux DL, Fojo AT. Mitotane enhances cytotoxicity of chemotherapy in cell lines expressing a multidrug resistance gene (mdr-1/P-glycoprotein) which is also expressed by adrenocortical carcinomas. J Clin Endocrinol Metab. 1991 Jul;73(1):18-29. doi: 10.1210/jcem-73-1-18.

  PMID: 1675220 BACKGROUND

• Cohn K, Gottesman L, Brennan M. Adrenocortical carcinoma. Surgery. 1986 Dec;100(6):1170-7.

  PMID: 3787475 BACKGROUND

MeSH Terms

Conditions

Adrenocortical Carcinoma

Interventions

Doxorubicin; Vincristine; Etoposide; Mitotane

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Adrenal Cortex Neoplasms; Adrenal Gland Neoplasms; Endocrine Gland Neoplasms; Neoplasms by Site; Adrenal Cortex Diseases; Adrenal Gland Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates; Vinca Alkaloids; Secologanin Tryptamine Alkaloids; Indole Alkaloids; Alkaloids; Heterocyclic Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Indolizidines; Indolizines; Podophyllotoxin; Tetrahydronaphthalenes; Naphthalenes; Glucosides; Hydrocarbons, Chlorinated; Hydrocarbons, Halogenated

Study Design

• Study Type: interventional
• Phase: phase 2
• Purpose: TREATMENT
• Sponsor Type: NIH

Study Record Dates

• First Submitted: November 3, 1999
• First Posted: November 4, 1999
• Study Start: August 1, 1993
• Study Completion: August 1, 2002
• Last Updated: March 4, 2008

Record last verified: 2002-08

Locations

US (1)