Surgery Plus Chemotherapy (Doxorubicin, Vincristine and Etoposide), Mitotane, and Tariquidar to Treat Adrenocortical Cancer

Launched by NATIONAL CANCER INSTITUTE (NCI) · Oct 9, 2003

Keywords

ClinConnect Summary

Adrenocortical cancer (ACC) is a rare tumor that is optimally treated with surgical resection. However, many patients present with unresectable disease and relapses are common after surgical resection creating a need for more effective systemic therapies. Several investigators have reported responses to a variety of chemotherapy agents, without a clear improvement in overall survival. A possible explanation for these disappointing results is the high levels of expression of P-glycoprotein (Pgp) seen in a majority of adrenocortical cancers. Pgp, a membrane protein that can function as a drug...

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ALL

Eligibility criteria

• * INCLUSION CRITERIA:
• • Pathologic confirmation of adrenocortical cancer by the Laboratory of Pathology, NCI
• • Diagnosis of recurrent, metastatic, or primary unresectable adrenocortical carcinoma.
• • Measurable disease at presentation.
• • A life expectancy of at least 3 months and Eastern Cooperative Oncology Group (ECOG) performance status less than or equal to 2.
• • Age greater than or equal to 18 years.
• • Last dose of chemotherapy or experimental therapy more than 4 weeks (6 weeks in the case of nitrosourea) prior to enrollment date.
• • Last radiotherapy treatment 4 weeks prior to starting treatment with this protocol and there must be sites of measurable disease that did not receive radiation.
• • Prior mitotane therapy is allowed. Patients do not need to be off mitotane therapy prior to starting this protocol.
• Organ and marrow function as defined below:
• • Total bilirubin less than or equal to 1.5 times ULN (upper limit of normal), unless the patient meets the criteria for Gilbert's Syndrome,
• • Aspartate aminotransferase (AST) less than or equal to 3 times ULN, Alanine aminotransferase (ALT) less than or equal to 3 times ULN
• • Creatinine clearance greater than or equal to 40 ml/min (measured in a timed urine collection) or serum creatinine less than or equal to 1.6 mg/dl
• • Absolute neutrophil count greater than or equal to 1000/mm\^3,
• • Platelet count greater than or equal to 100,000/mm\^3
• • Ability to understand and sign an informed consent document.
• • Ability and willingness to follow the guidelines of the clinical protocol including visits to National Cancer Institute (NCI), Bethesda, Maryland for treatment and follow up visits.
• • The effects of chemotherapy on the developing human fetus are potentially harmful therefore women of childbearing potential and men must agree to use adequate contraception (hormonal or barrier methods) during the study and for a period of 1 month after the last dose of chemotherapy.
• EXCLUSION CRITERIA:
• • Patients with adrenocortical tumors potentially curable by surgical excision alone as determined by the Principal Investigator in discussions with the surgical consultants.
• • Uncontrolled illness including, but not limited to symptomatic congestive heart failure, unstable angina pectoris, seizure disorder, or psychiatric illness that may limit compliance with study requirements. These illnesses may be exacerbated by chemotherapy.
• • Untreated brain metastases (or local treatment of brain metastases within the last 6 months) due to the poor prognosis of these patients and difficulty ascertaining the cause of neurologic toxicities.
• • Pregnancy due to the possible adverse effects on the developing fetus.
• • Lactating women who are breast-feeding due to the possibility of transmitting chemotherapy to the child.
• • The presence of a second malignancy, other than squamous cell carcinoma of the skin or in situ cervical cancer because it will complicate the primary objective of the study. Cancer survivors who have been free of disease for at least two years can be enrolled in this study.
• • Currently receiving treatment (which cannot be discontinued) with the following agents: diltiazem, nicardipine, phenothiazines, phenytoin, or verapamil because these are Pgp inhibitors and will interfere with the primary objective of the study.
• • Ejection fraction less than 40% as determined by multi-gated acquisition scan (MUGA), echocardiogram (Echo), or cardiac magnetic resonance imaging (MRI) in patients with a clinical history suggestive of systolic dysfunction.