Protocol Number: 04-C-0011

Title:

A Study of Combination Chemotherapy & Surgical Resection in the Tx of Adrenocortical Cancer: Mitotane & Continuous Infusion Doxorubicin, Vincristine & Etoposide w/the P-glycoprotein Antagonist, Tariquidar (XR9576), Before & After Surgical Resection

Number:

04-C-0011

Summary:

Background:

-There are no effective systemic therapies for unresectable or relapsed adrenocortical cancer (ACC).

-High levels of expression of P-glycoprotein (Pgp) are observed in a majority of adrenocortical cancers.

-Pgp can function as a drug efflux pump lowering the intracellular concentrations of various drugs and has been implicated as a mechanism of drug resistance.

-A possible explanation for the failure of a prior NCI study (referred to as MAVE) to achieve a higher response rate may be that mitotane was unable to inhibit Pgp.

-Tariquidar (XR9576) has been proven to inhibit Pgp in humans with minimal toxicity alone or in combination with chemotherapy.

Objectives:

-Compare the response rate and progression free survival in recurrent, metastatic, or primary unresectable ACC treated with the combination of tariquidar, mitotane, and infusional doxorubicin, vincristine, and etoposide with the results observed in a previous trial with the same chemotherapy regimen without tariquidar.

-Determine the overall survival rate in the patients receiving tariquidar.

-Determine the safety of the combination of tariquidar, mitotane, and infusional doxorubicin, vincristine, and etoposide.

-Evaluate Pgp inhibition by using circulating CD 56+ mononuclear cells in an assay that measures the accumulation of rhodamine 123 and by performing 99mTc Sestamibi Scans to assess the accumulation of the radioisotope in tumors and in normal tissues in patients receiving tariquidar.

Eligibility:

-Age greater than 18.

-Pathological confirmation of adrenocortical cancer.

-Measurable disease at presentation.

-Last dose of chemotherapy or last radiotherapy treatment more than 4 weeks prior to starting treatment with this protocol.

-Prior mitotane therapy is allowed.

Design:

-Phase II study.

-Tariquidar will be administered over 30 minutes on days 1 and 3 on every 21 days cycle. Doxorubicin, vincristine, and etoposide will be continuously infused on days 1 through 4 every 21 days. Mitotane will be administered daily.

-Re-staging radiography will be performed every 2 cycles.

-Surgical excision of tumors can be performed on patients at the time of study entry, on patients whose tumor responds to chemotherapy and on patient with a mixed response if both the PI and Surgical Consult agree that this is the best strategy.

Sponsoring Institute:

National Cancer Institute (NCI)

Recruitment Detail

Type: No longer recruiting/follow-up only

Gender: Male & Female

Referral Letter Required: No

Population Exclusion(s): Children

Eligibility Criteria: This study is not currently recruiting new subjects. If you have questions about participating in a study, please contact the Patient Recruitment and Public Liaison Office, CC.

Special Instructions:

Currently Not Provided

Keyword(s):

P-glycoprotein Inhibition

Drug Resistance Reversal

Pharmacodynamics

Molecular Target

Endocrine Cancer

Adrenocortical Cancer

ACC

Adrenocortical Tumor

Recruitment Keyword(s):

None

Condition(s):

Adrenal Cortex Neoplasms

Investigational Drug(s):

XR9576 (Taruquidar)

Investigational Device(s):

None

Interventions:

Drug: XR9576 (Taruquidar)

Supporting Site:

National Cancer Institute

Contact(s):

This study is not currently recruiting new subjects. If you have questions about participating in a study, please contact the Patient Recruitment and Public Liaison Office, CC.

Citation(s):

Plager JE. Carcinoma of the adrenal cortex: clinical description, diagnosis, and treatment. Int Adv Surg Oncol. 1984;7:329-53.

Luton JP, 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.

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

• Questions about participating in a study, please contact the Patient Recruitment and Public Liaison Office, CC.
• Technical questions regarding the Clinical Center web site, please contact the Department Clinical Research Informatics, CC.

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