Protocol Number: 08-C-0176

Title:

First International Randomized Trial in Locally Advanced and Metastatic Adrenocortical Carcinoma Treatment (FIRM-ACT) Etoposide, Doxorubicin, Cisplatin and Mitotane vs Streptozotocin and Mitotane

Number:

08-C-0176

Summary:

Background:

- There is no medical consensus about the best treatment for advanced adrenocortical cancer (ACC) that cannot successfully be treated with surgery alone.

- In 2003, the International Consensus Conference on Adrenal Cancer recommended two chemotherapy regimens - etoposide, doxorubicin, cisplatin plus mitotane and streptozotocin plus mitotane- as the best choices until better data could be obtained. All the drugs in the two options have been shown effective against advanced ACC, but they have different side effects.

Objectives:

- To determine which of the chemotherapy regimens described above is best to start with in patients with ACC that cannot be surgically removed.

- To determine if there is a way to identify which patients will respond to a certain therapy.

Eligibility:

- Patients 18 years of age and older from the USA, Scandinavia, Germany, Italy, France, The Netherlands, Belgium, the UK, Canada and Australia who have adrenocortical cancer that cannot be cured with surgery alone.

Design:

- Chemotherapy: Patients are randomly assigned to start with one of the two study regimens. Patients whose tumor continues to grow during treatment are offered the alternative therapy. All patients receive daily tablets of mitotane. In addition, they have one of the following two regimens:

- Streptozotocin every 3 weeks for up to six cycles. The first cycle is given on days 1, 2, 3, 4 and 5 and subsequent cycles are given on day 1 only.

- Cisplatin plus etoposide plus doxorubicin every 4 weeks for up to six cycles. Doxorubicin is given on day 1, etoposide is given on days 2, 3 and 4 and cisplatin is given on days 3 and 4.

- CT scans of the chest, abdomen and pelvis approximately once every 8 weeks.

- Physical examination, routine blood tests and a check of side effects at the start of each treatment cycle.

- Blood test to determine if the hormones produced by some adrenocortical cancers have any effect on the immune system.

- Analysis of genetic markers in blood and tumor tissue for comparison with tumor growth and patient survival to determine if this can help identify which patients will respond to a certain therapy.

- Optional procedures:

- Storage of blood and tissue samples for future research.

- Completion of quality-of-life questionnaires every 2 months.

Sponsoring Institute:

National Cancer Institute (NCI)

Recruitment Detail

Type: Participants currently recruited/enrolled

Gender: Male & Female

Referral Letter Required: No

Population Exclusion(s): Children

Eligibility Criteria:

INCLUSION CRITERIA:

Clinical inclusion criteria

-Histologically confirmed diagnosis of adrenocortical carcinoma.

-Locally advanced or metastatic disease not amenable to radical surgery resection (Stage III-IV).

Other inclusion criteria

-Radiologically monitorable disease.

-ECOG performance status 0-2.

-Life expectancy greater than 3 months.

-Age greater than or equal to 18 years.

-Adequate bone marrow reserve (neutrophils greater than or equal to 1500/mm(3) and platelets greater than or equal to 100.000/mm(3)).

-Effective contraception in pre-menopausal female and male patients.

-Patient's written informed consent.

-Ability to comply with the protocol procedures (including availability for follow-up visits).

-Previous palliative surgery, radiotherapy or radiofrequency ablation is acceptable as long as radiologically monitorable disease is verifiably afterwards.

EXCLUSION CRITERIA:

-History of prior malignancy, except for cured non-melanoma skin cancer, cured in situ cervical carcinoma, or other cancers treated with no evidence of disease for at least five years.

-Previous cytotoxic chemotherapy (prior therapy with mitotane is allowed) for adrenocortical carcinoma.

-Renal insufficiency (serum creatinine greater than or equal to 2 mg/dl or creatinine clearance less than or equal to 50 ml/min). (see NCI Appendix).

-Hepatic insufficiency (serum bilirubin greater than or equal to 2 times the institutional upper limit of normal range and/or serum transaminases greater than or equal to 3 times the institutional upper limit of normal range; exception: in patients on mitotane transaminase levels up to 5 times the institutional upper limit of normal range are acceptable) (see NCI Appendix).

-Pregnancy or breast feeding.

-Known hypersensitivity to any drug included in the treatment protocol.

-Presence of active infection.

-Any other severe clinical condition that in the judgment of the local investigator would place the patient at undue risk or interfere with the study completion.

-Decompensated heart failure (ejection fraction less than 50 percent), myocardial infarction or revascularization procedure during the last 6 months, unstable angina pectoris, and uncontrolled cardiac arrhythmia.

-Current treatment with other experimental drugs and/or previous participation in clinical trials with other experimental agents for adrenocortical carcinoma.

-Prisoners

Special Instructions:

Currently Not Provided

Keywords:

Adrenocortical Cancer

Randomized Trial

Recruitment Keyword(s):

Adrenocortical Cancer

ACC

Condition(s):

Adenocortical Cancer

Investigational Drug(s):

None

Investigational Device(s):

None

Intervention(s):

Drug: Mitotane

Drug: Streptozocin

Drug: Doxorubicin

Drug: Etoposide

Drug: Cisplatin

Supporting Site:

National Cancer Institute

Contact(s):

NCI Referral Office
National Institute of Health Clinical Center (CC), 9000 Rockville Pike, Bethesda, Maryland 20892, United States: NCI Clinical Trials Referral Office
Phone: 1-888-NCI-1937
Fax: Not Listed
Electronic Address: ncicssc@mail.nih.gov

Citation(s):

Aaronson NK, Ahmedzai S, Bergman B, Bullinger M, Cull A, Duez NJ, Filiberti A, Flechtner H, Fleishman SB, de Haes JC, et al. The European Organization for Research and Treatment of Cancer QLQ-C30: a quality-of-life instrument for use in international clinical trials in oncology. J Natl Cancer Inst. 1993 Mar 3;85(5):365-76.

Abraham J, Bakke S, Rutt A, Meadows B, Merino M, Alexander R, Schrump D, Bartlett D, Choyke P, Robey R, Hung E, Steinberg SM, Bates S, Fojo T. A phase II trial of combination chemotherapy and surgical resection for the treatment of metastatic adrenocortical carcinoma: continuous infusion doxorubicin, vincristine, and etoposide with daily mitotane as a P-glycoprotein antagonist. Cancer. 2002 May 1;94(9):2333-43.

Allolio B, Hahner S, Weismann D, Fassnacht M. Management of adrenocortical carcinoma. Clin Endocrinol (Oxf). 2004 Mar;60(3):273-87.

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