IMC-A12 With Mitotane vs Mitotane Alone in Recurrent, Metastatic, or Primary ACC That Cannot Be Removed by Surgery
Condition: Recurrent Adrenocortical Carcinoma; Stage III Adrenocortical Carcinoma; Stage IV Adrenocortical Carcinoma
MeSH terms: Carcinoma; Adrenocortical Carcinoma
Intervention: IMC-A12; mitotane
Intervention description: Given IV; Given orally
Intervention MeSH terms: Mitotane
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 20.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

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.
    

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