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

NCT01334710 | Terminated Phase 2 Results DMC

• 2 other identifiers: IRB00047003WCI1887-10
• Study Type: interventional
• Target: 3
• Locations: 1 country
• Sites: 3

Brief 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.

Conditions

Liver Cancer

Keywords

Liver cancer

Outcome Measures

Primary Outcomes (1)

• Comparison of MRI/CT Scans to Pre-treatment Scan

  Efficacy will be measured by evaluating the number of patients who do not have disease progression (measured by CT or MRI scan) 5 months after starting treatment. Assessment of the endpoint of disease progression will be performed every 2 months using either CT or MRI scan. Participants will remain on the study until either evidence of disease progression or unacceptable side effects develop. This period is expected to be on the average 6 months long.

  6 months

Secondary Outcomes (1)

• Toxicity Assessment

  28 days from study entry

Study Arms (1)

Sorafenib and OSI-906

EXPERIMENTAL

This is a single arm phase II trial designed to evaluate the effect of adding OSI-906 to sorafenib in patients with hepatocellular cancer. The study is designed to evaluate the safety of the regimen in the first six patients.

Drug: Sorafenib and OSI-906

Interventions

Sorafenib and OSI-906 DRUG

Sorafenib - 400 mg twice daily OSI-906 - 150 mg twice daily

Also known as: Nexavar

Sorafenib and OSI-906

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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).

Sponsors & Collaborators

• Emory University: lead
• OSI Pharmaceuticals: collaborator

Study Sites (3)

Emory University Winship Cancer Institute

Atlanta, Georgia, 30322, United States

Location

University of Michigan

Ann Arbor, Michigan, 48109, United States

Location

Ohio State University

Columbus, Ohio, 43210, United States

Location

MeSH Terms

Conditions

Liver Neoplasms

Interventions

Sorafenib; 3-(8-amino-1-(2-phenylquinolin-7-yl)imidazo(1,5-a)pyrazin-3-yl)-1-methylcyclobutanol

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Liver Diseases

Intervention Hierarchy (Ancestors)

Phenylurea Compounds; Urea; Amides; Organic Chemicals; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Niacinamide; Nicotinic Acids; Acids, Heterocyclic; Heterocyclic Compounds; Pyridines; Heterocyclic Compounds, 1-Ring

Limitations and Caveats

A second trial evaluating OSI906 in hepatocellular cancer was being run in parallel to this trial. There were safety signals in the second trial which led to stopping this trial.

Results Point of Contact

• Title: Dr. Bassel El-Rayes
• Organization: Emory University

belraye@emory.edu

404-778-1900

Study Officials

• Bassel El-Rayes, MD

  Emory University Winship Cancer Institute

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD

Study Record Dates

• First Submitted: April 6, 2011
• First Posted: April 13, 2011
• Study Start: March 1, 2011
• Primary Completion: August 1, 2011
• Study Completion: December 1, 2011
• Last Updated: November 21, 2017
• Results First Posted: October 12, 2012

Record last verified: 2017-10

Locations

US (3)