Basic Trial Information
Trial Description
     Summary
     Further Trial Information
     Eligibility Criteria
Trial Contact Information

Basic Trial Information

Trial Description

Summary

This randomized phase II trial is studying mitotane and IMC-A12 to see how well they work compared with mitotane alone in treating patients with recurrent, metastatic, or primary adrenocortical cancer that cannot be removed by surgery. Drugs used in chemotherapy, such as mitotane, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Monoclonal antibodies, such as IMC-A12, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. It is not yet known whether mitotane is more effective with or without monoclonal antibody IMC-A12 in treating adrenocortical cancer

Further Study Information

PRIMARY OBJECTIVES:

I. Compare the progression-free survival (PFS) rate in patients with recurrent, metastatic, or primary unresectable adrenocortical carcinoma treated with mitotane with vs without anti-IGF-1R recombinant monoclonal antibody IMC-A12 (IMC-A12).

SECONDARY OBJECTIVES:

I. Compare the response rates in these patients using Response Evaluation Criteria in Solid Tumor (RECIST) criteria.

II. Compare the change in tumor size from baseline to 12 weeks in these patients.

III. Compare the overall trajectories in tumor growth in these patients.

TERTIARY OBJECTIVES:

I. Define predictive markers of response or insensitivity to IMC-A12. II. Define pharmacodynamic markers of IMC-A12. III. Determine whether tumor expression of IGF-IR and activation of downstream signaling in archival tumor tissue samples predict efficacy of IMC-A12.

OUTLINE: This is a multicenter study that includes a single-arm safety evaluation phase followed by a randomized phase. Initially, patients are enrolled in the safety evaluation phase. If ≤ 6 of 20 patients experience a dose-limiting toxicity, then the study may proceed to the randomized phase.

SAFETY EVALUATION PHASE: Patients receive oral mitotane once or twice daily and anti-IGF-1R recombinant monoclonal antibody IMC-A12 IV over 1 hour once every 2 weeks in the absence of disease progression or unacceptable toxicity.

RANDOMIZED PHASE: Patients are stratified according to participating center. Patients are randomized to 1 of 2 treatment arms.

ARM I: Patients receive oral mitotane once or twice daily in the absence of disease progression or unacceptable toxicity. Patients with documented disease progression may cross over and receive treatment on arm II.

ARM II: Patients receive mitotane as in arm I and anti-IGF-1R recombinant monoclonal antibody IMC-A12 IV over 1 hour once every 2 weeks in the absence of disease progression or unacceptable toxicity.

Archival frozen tissue blocks, unstained tumor tissue slides from archival paraffin blocks, plasma samples, and urine samples may be collected and stored for future correlative biomarker studies.

After completion of study therapy, patients are followed up for 6 months.

Eligibility Criteria

Inclusion Criteria:

• Histologically confirmed adrenocortical carcinoma

• Documented unresectable recurrent, unresectable advanced, or metastatic disease

• At least 1 lesion that can be accurately measured by RECIST criteria as ≥ 20 mm by conventional radiologic techniques or as ≥ 10 mm by spiral CT scan or MRI

• Patients with disease in an irradiated field as the only site of measurable disease allowed provided there has been a clear progression of the lesion

• No tumors potentially resectable by surgical excision alone

• No known or suspected leptomeningeal disease or brain metastases

• ECOG performance status 0-2

• Life expectancy ≥ 12 weeks

• ANC ≥ 1,500/mm^3

• Platelet count ≥ 100,000/mm^3

• Hemoglobin ≥ 9 g/dL (transfusion allowed)

• Serum creatinine ≤ 1.5 times upper limit of normal (ULN) OR calculated creatinine clearance ≥ 60 mL/min

• AST or ALT ≤ 3 times ULN

• Total bilirubin ≤ 1.5 times ULN

• HbA1c < 8 within the past 4 weeks

• Not pregnant or nursing

• Negative pregnancy test

• Fertile patients must use effective contraception during and for 3 months after completion of study therapy

• Able to take oral medications

• No poor gastrointestinal absorption

• Patients with diabetes mellitus are eligible provided they meet all of the following criteria:

• Blood glucose is normal (random glucose ≤ 150 mg/dL)

• HgbA1c ≤ 8 within the past 4 weeks

• On a stable dietary or therapeutic regimen for the past 2 months

• No active uncontrolled infection

• No severe disease or condition that, in the judgement of the investigator, would make the patient inappropriate for study participation, including, but not limited to:

• Bleeding diathesis

• Uncontrolled chronic kidney or liver disease

• Uncontrolled diabetes

• History of cardiac history

• Myocardial infarction within the past 6 months

• Congestive heart failure

• Unstable angina pectoris

• Cardiac arrhythmia

• Uncontrolled hypertension

• No current malignancy or previous malignancy with a disease-free interval of < 2 years at the time of diagnosis

• Patients with adequately treated basal cell or squamous cell carcinoma of the skin, carcinoma in situ of the cervix or skin, or stage A low-grade prostate cancer are eligible

• No known hypersensitivity to monoclonal antibody therapy or mitotane

• No known HIV or hepatitis B or C infection

• No serious medical or psychiatric disorder that would interfere with patient safety or informed consent

• All significant toxic effects of prior surgery resolved to ≤ grade 1 according to NCI CTCAE v. 3.0 criteria

• Mitotane for < 8 weeks prior to study entry AND tolerated it well

• No prior IGFR-directed therapy

• No prior systemic antitumor therapy (cytotoxic chemotherapy, biologic, immunotherapy, or targeted therapy)

• Prior incomplete surgical resections or radiofrequency ablation or radiotherapy will not be considered as prior therapy provided measurable sites of disease remain

• Prior adjuvant chemotherapy or mitotane will not be considered as prior antitumor therapy unless it was completed < 6 months before study enrollment

• No prior radiotherapy to > 20% of bone marrow

• More than 4 weeks since prior and no concurrent radiotherapy

• Radiotherapy for palliation of symptoms related to metastases is permitted provided that it is > 4 weeks from study initiation, and does not involve target/measureable lesions that are followed for drug treatment response evaluation

• No concurrent mitotane ≥ 8 weeks prior to study

• No concurrent tumor resection or tumor-directed surgery

• No other concurrent anticancer or investigational therapy

Trial Contact Information

Trial Lead Organizations/Sponsors

National Cancer Institute

Gary Hammer

Principal Investigator

Link to the current ClinicalTrials.gov record.
NLM Identifer NCT00778817
Information obtained from ClinicalTrials.gov on December 23, 2012

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