Intervention: Mitotane
Trial phase: Phase 2
ATC code: L01XX23
SMILES: Clc1ccc(C(c2ccccc2Cl)C(Cl)Cl)cc1
Sex: All
Age groups: Adult | Older Adult
Healthy volunteers: No
Participants at risk: 20
Group description: 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.
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