A Phase II Trial of OSI-906 and Sorafenib in Advanced Hepatocellular Cancer

• Status: Terminated
• Trial end date: 2011-12-01
• Target enrollment: 0
• Participant gender: All

Summary

The purpose of this study is to evaluate the effect of combining a new investigational drug (OSI-906) with a standard drug (sorafenib) on the control of liver cancer (hepatocellular cancer). Sorafenib (brand name Nexavar®) is a drug that is approved for the treatment of advanced liver cancer. It works by stopping the growth of new blood vessels around the tumor. OSI-906 is an investigational agent that works by inhibiting the effects of a growth hormone on the cancer. The safety and efficacy of combining OSI-906 and sorafenib in the treatment of liver cancer risk not known. The current study will confirm the safety of the combination in the first six patients and evaluate the activity of the combination in patients with advanced liver cancer.

In addition, the study will aim at collecting blood samples from patients to evaluate the level of OSI-906 in patients receiving the combination of the two drugs. The study also will collect samples of the tumor to evaluate for markers that can predict in which patient the combination is effective.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Emory University
• Collaborator: OSI Pharmaceuticals
• Treatments: Niacinamide; Sorafenib

Criteria

Inclusion Criteria:

• Patients with measurable, histological diagnosis of HCC and whose disease is not amenable to surgical or regional therapy.

• Prior allowed therapy: surgery, regional therapy (if more than 6 weeks have elapsed from therapy and if there is an indicator lesion outside the treated area or if there is clear evidence of progression in the treated lesion), or adjuvant sorafenib (if disease relapsed more than 6 months after completion of adjuvant therapy).

• Patient with cirrhosis must have Childs-Pugh score of either A or B7.

• Performance status of 0-2.

• Organ function requirements: hemoglobin > 9.0mg/dl; granulocyte count > 1,000 /mm³ , platelets > 40,000/mm³ , alanine aminotransferase (ALT)/aspartate aminotransferase (AST) up to 5 times the institutional upper limit of normal, alkaline phosphatase < 4 times the institutional upper limit of normal and serum creatinine < 2mg/dl.

• Patients must provide verbal and written informed consent to participate in the study.

• Patients - both males and females - with reproductive potential (ie, menopausal for less than 1 year and not surgically sterilized) must 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 registration.

Exclusion Criteria:

• Patients with mixed histology or fibrolamellar variant.

• Fasting glucose >150 mg/dl and any prior history of diabetes.

• Patients with Type 1 diabetes mellitus or Type 2 diabetes mellitus currently requiring insulinotropic or insulin therapy.

• Prior systemic therapy for metastatic disease.

• Corrected QT (QTc) interval > 450 msec at baseline.

• Concomitant drugs that prolong the QTc interval.

• Significant cardiac disease defined as: congestive heart failure (NYHA class 2 or higher) or active coronary artery disease (MI within 6 months of study enrollment).

• Pregnant or breast-feeding females.

• Serious active infections.

• Encephalopathy.

• Uncontrolled ascites defined as symptomatic ascites not controlled with diuretic treatments.

• Active second primary malignancy except for is situ carcinoma of the cervix or adequately treated basal cell carcinoma of the skin within less than one year of enrollment into the study.

• Use of drugs that have a known risk of causing Torsades de Pointes (TdP) are prohibited within 14 days prior to enrollment.

• Use of the potent CYP1A2 inhibitors such as ciprofloxacin and fluvoxamine. Other less potent CYP1A2 inhibitors/inducers are not excluded.

• Patients with a history of poorly controlled gastrointestinal disorders that could affect the absorption of study drug (e.g., Crohn's disease, ulcerative colitis, etc).