A Phase II Trial of OSI-906 and Sorafenib in Advanced Hepatocellular Cancer
Condition: Liver Cancer
MeSH terms: Liver Neoplasms; Carcinoma, Hepatocellular
Intervention: Sorafenib and OSI-906
Intervention description: Sorafenib - 400 mg twice daily OSI-906 - 150 mg twice daily
Intervention MeSH terms: Sorafenib
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 3.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Liver cancer

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.
    

Eligibility 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).