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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

Primary Purpose

Adrenal Cortical Carcinoma

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
doxorubicin, vincristine, and etoposide with mitotane
Sponsored by
National Cancer Institute (NCI)
About
Eligibility
Locations
Outcomes
Full info

About this trial

This is an interventional treatment trial for Adrenal Cortical Carcinoma focused on measuring Multidrug Resistance, Reversal of Drug Resistance, P-Glycoprotein, MDR-1

Eligibility Criteria

undefined - undefined (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • National Cancer Institute (NCI)

Outcomes

Primary Outcome Measures

Secondary Outcome Measures

Full Information

First Posted
November 3, 1999
Last Updated
March 3, 2008
Sponsor
National Cancer Institute (NCI)
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1. Study Identification

Unique Protocol Identification Number
NCT00001339
Brief 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
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 Type
Interventional

2. Study Status

Record Verification Date
August 2002
Overall Recruitment Status
Completed
Study Start Date
August 1993 (undefined)
Primary Completion Date
undefined (undefined)
Study Completion Date
August 2002 (undefined)

3. Sponsor/Collaborators

Name of the Sponsor
National Cancer Institute (NCI)

4. Oversight

5. Study Description

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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Adrenal Cortical Carcinoma
Keywords
Multidrug Resistance, Reversal of Drug Resistance, P-Glycoprotein, MDR-1

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Enrollment
42 (false)

8. Arms, Groups, and Interventions

Intervention Type
Drug
Intervention Name(s)
doxorubicin, vincristine, and etoposide with mitotane

10. Eligibility

Sex
All
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Facility Information:
Facility Name
National Cancer Institute (NCI)
City
Bethesda
State/Province
Maryland
ZIP/Postal Code
20892
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
2325710
Citation
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.
Results Reference
background
PubMed Identifier
1675220
Citation
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.
Results Reference
background
PubMed Identifier
3787475
Citation
Cohn K, Gottesman L, Brennan M. Adrenocortical carcinoma. Surgery. 1986 Dec;100(6):1170-7.
Results Reference
background

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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

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