Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outcomes
Outline
Trial Contact Information
Related Information
Registry Information

Alternate Title

Tariquidar, Mitotane, Doxorubicin, Vincristine, and Etoposide Plus Surgery in Treating Patients With Recurrent, Metastatic, or Primary Unresectable Adrenocortical Cancer

Basic Trial Information

Phase	Type	Status	Age	Sponsor	Protocol IDs
Phase II	Treatment	Closed	18 and over	NCI	NCI-04-C-0011 NCT00073996

Special Category: NCI Web site featured trial

Objectives

Primary

1. Compare response rate and progression-free survival of patients with recurrent, metastatic, or primary unresectable adrenocortical cancer treated with combination chemotherapy comprising tariquidar, mitotane, doxorubicin, vincristine, and etoposide and surgery vs historical controls treated with the same chemotherapy regimen but without tariquidar.
2. Determine the overall survival of patients treated with this regimen.

Secondary

1. Determine the safety of this regimen in these patients.
2. Correlate DNA microarray analysis data with clinical presentation (including functional status of the tumor), response to therapy, and long-term clinical outcome in patients treated with this regimen.

Entry Criteria

Disease Characteristics:

• Histologically confirmed adrenocortical carcinoma
  • Recurrent, metastatic, or primary unresectable disease



• No tumors potentially curable by surgical excision alone



• Measurable disease at presentation



• No untreated brain metastases OR local treatment of brain metastases within the past 6 months

Prior/Concurrent Therapy:

Biologic therapy

• Not specified

Chemotherapy

• More than 4 weeks since prior chemotherapy (6 weeks for nitrosoureas)
• Prior mitotane allowed
  • Patients do not need to be off mitotane before starting this study

Endocrine therapy

• Not specified

Radiotherapy

• At least 4 weeks since prior radiotherapy
  • Must have sites of measurable disease that did not receive radiotherapy

Surgery

• Not specified

Other

• More than 4 weeks since prior experimental therapy
• No concurrent treatment with any of the following:
  • Diltiazem
  • Nicardipine
  • Phenothiazines
  • Phenytoin
  • Verapamil

Patient Characteristics:

Age

• 18 and over

Performance status

• ECOG 0-2

Life expectancy

• At least 3 months

Hematopoietic

• Absolute neutrophil count at least 1,000/mm³
• Platelet count at least 100,000/mm³

Hepatic

• Bilirubin no greater than 1.5 times upper limit of normal (ULN) (except for patients with Gilbert’s syndrome)
• AST and ALT no greater than 3 times ULN

Renal

• Creatinine clearance at least 40 mL/min

  OR

• Creatinine no greater than 1.6 mg/dL

Cardiovascular

• No symptomatic congestive heart failure
• No unstable angina pectoris
• Ejection fraction at least 40% by MUGA, echocardiogram, or cardiac MRI for patients with a clinical history suggestive of systolic dysfunction

Other

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception during and for 1 month after study participation
• No seizure disorder
• No psychiatric illness that would preclude study compliance
• No other uncontrolled illness that would preclude study participation
• No other malignancy within the past 2 years except squamous cell skin cancer or carcinoma in situ of the cervix

Expected Enrollment

A total of 50 patients will be accrued for this study within 3 years.

Outcomes

Response rate (partial or complete)
Progression-free survival

Assessment of the extent of in vivo P-glycoprotein (Pgp) inhibition in CD56-positive cells as measured by CD56-positive cell assay with rhodamine
In vivo imaging with 99mTc-sestamibi and assessment of Pgp inhibition
Correlation of the pattern of gene expression found with the cDNA microarray with response and survival
Correlation of Pgp expression as measured by quantitative polymerase chain reaction and immunohistochemistry with response

Outline

Patients receive oral mitotane daily beginning on day 1 (and continuing during entire treatment period), tariquidar IV over 30 minutes on days 1 and 3, and doxorubicin, vincristine, and etoposide IV continuously over 96 hours on days 1-4. Courses repeat every 3 weeks in the absence of disease progression or unacceptable toxicity. Patients achieving a complete response (CR) receive 2 additional treatment courses beyond CR.

Patients may undergo surgery, if possible, after study therapy. Patients without residual disease who respond to chemotherapy (administered prior to surgery) receive 2 additional courses of chemotherapy (as above) beginning 3 weeks after surgery. Patients with or without residual disease who do not respond to chemotherapy (administered prior to surgery) are removed from the study and may receive single-agent mitotane daily beginning as soon as medically indicated after surgery and continuing indefinitely. Patients with residual disease who respond to chemotherapy (administered prior to surgery) receive additional chemotherapy (as above) beginning as soon as medically indicated after surgery.

Patients are followed every 3-12 months for up to 7 years.

Trial Contact Information

Trial Lead Organizations

NCI - Center for Cancer Research

Antonio Fojo, MD, PhD, Principal investigator		Ph: 301-402-1357 Email: tfojo@helix.nih.gov
Maureen Edgerly, RN, Study coordinator		Ph: 301-435-5604 Email: edgerlym@mail.nih.gov

Related Information

Featured trial article

Registry Information
Official Title		A Study Of Combination Chemotherapy And Surgical Resection In The Treatment Of Adrenocortical Cancer: Mitotane And Continuous Infusion Doxorubicin, Vincristine And Etoposide With The P-glycoprotein Antagonist, Tariquidar (XR9576), Before And After Surgical Resection
Trial Start Date		2004-12-01
Registered in ClinicalTrials.gov		NCT00073996
Date Submitted to PDQ		2003-10-20
Information Last Verified		2008-04-15