IMC-A12 With Mitotane vs Mitotane Alone in Recurrent, Metastatic, or Primary ACC That Cannot Be Removed by Surgery

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