A Randomized, Double-blind, Placebo-controlled, Phase 3 Study of OSI-906 in Patients With Locally Advanced or Metastatic Adrenocortical Carcinoma
- Histologically confirmed adrenocortical carcinoma that is locally advanced or
metastatic and not amenable to surgical resection.
- Measurable disease according to Response Evaluation Criteria in Solid Tumors (RECIST)
- Eastern Cooperative Oncology Group (ECOG) performance status (PS) <= 2
- Predicted life expectancy >= 12 weeks.
- At least 1 but no more than 2 prior drug regimens (including molecular targeted
therapy, systemic cytotoxic chemotherapy, biologics, and/or vaccines) for locally
- A minimum of 3 weeks must have elapsed between the end of prior treatment and
- All patients must have received prior mitotane, either as neoadjuvant, adjuvant, or
locally advanced/metastatic therapy.
- Adjuvant and neoadjuvant mitotane therapy will not be counted as prior drug regimens
or as systemic cytotoxic chemotherapy.
- Prior radiation therapy is permitted provided patients have recovered from the acute,
toxic effects of radiotherapy prior to randomization.
- A minimum of 21 days must have elapsed between the end of radiotherapy and
- Prior surgery is permitted provided that adequate wound healing has occurred prior to
- Fasting glucose < = 150 mg/dL (8.3 mmol/L).
- Adequate hematopoietic, hepatic, and renal function defined as follows: Neutrophil
count >= 1.5 x 10^9 /L;
- Platelet count >= 100 x 10^9 /L;
- Bilirubin <= 1.5 x Upper Limit of Normal (ULN);
- AST and ALT <= 2.5 x ULN, or <= 5 x ULN if patient has documented liver metastases or
received prior mitotane therapy; and
- Serum creatinine <= 1.5 x ULN or <= 2.0 x ULN if the patient has received prior
- Patients, both males and females, with reproductive potential (ie, menopausal for
less than 1 year and not surgically sterilized) must agree to practice effective
contraceptive measures throughout the study.
- Women of childbearing potential must provide a negative pregnancy test (serum or
urine) within 14 days prior to randomization.
- Patients must provide verbal and written informed consent to participate in the
- Radiologically-confirmed progressive disease within 6 months prior to randomization.
- Concurrent use of non-insulinotropic oral antihyperglycemic therapy is permitted if
the dose has been stable for >= 4 weeks at the time of randomization.
- Type 1 diabetes mellitus or Type 2 diabetes mellitus currently requiring
insulinotropic or insulin therapy.
- Prior IGF-1R inhibitor therapy.
- Malignancy other than ACC within the past 3 years. Exceptions: resected basal cell
or squamous cell carcinoma of the skin; cured in situ cervical carcinoma; cured
ductal carcinoma in situ of the breast; and/or cured superficial bladder cancer.
- History of significant cardiovascular disease unless the disease is well-controlled.
- Significant cardiac diseases includes second/third degree heart block; clinically
significant ischemic heart disease; mean QTcF interval > 450 msec at screening;
- poorly controlled hypertension; congestive heart failure of New York Heart
Association (NYHA) Class II or worse (slight limitation of physical activity;
comfortable at rest, but ordinary physical activity results in fatigue, palpitation,
- History of cerebrovascular accident (CVA) within 6 months prior to randomization or
that resulted in ongoing neurologic instability.
- Use of drugs that have a risk of causing QT interval prolongation within 14 days
prior to Day 1 dosing.
- Active infection or serious underlying medical condition (including any type of
active seizure disorder within 12 months prior to randomization) that would impair
the ability of the patient to receive study drug.
- History of any psychiatric condition that might impair the patient's ability to
understand or to comply with the requirements of the study or to provide informed
- Pregnant or breast-feeding females.
- Symptomatic brain metastases that are not stable, require steroids, are potentially
life threatening, or that have required radiation within 28 days prior to
- History of allergic reactions attributed to compounds of similar chemical or biologic
composition to study drug.