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

This study has been terminated.
(safety issue observed on another hepatocellular study using OSI906)
Sponsor:
Collaborator:
OSI Pharmaceuticals
Information provided by (Responsible Party):
Bassel El-Rayes, Emory University
ClinicalTrials.gov Identifier:
NCT01334710
First received: April 6, 2011
Last updated: November 18, 2013
Last verified: November 2013
  Purpose

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.


Condition Intervention Phase
Liver Cancer
Drug: Sorafenib and OSI-906
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase II Trial of OSI-906 and Sorafenib in Advanced Hepatocellular Cancer

Resource links provided by NLM:


Further study details as provided by Emory University:

Primary Outcome Measures:
  • Comparison of MRI/CT Scans to Pre-treatment Scan [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • Toxicity Assessment [ Time Frame: 28 days from study entry ] [ Designated as safety issue: Yes ]
    Evaluate the proportion of participants treated with OSI-906 and sorafenib who develop serious adverse events.


Enrollment: 3
Study Start Date: March 2011
Study Completion Date: December 2011
Primary Completion Date: August 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Sorafenib and OSI-906
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
Sorafenib - 400 mg twice daily OSI-906 - 150 mg twice daily
Other Name: Nexavar

Detailed Description:

The purpose of the trial is first to evaluate the safety of the combination of OSI-906 and sorafenib in patients with HCC. Patients will be treated in groups of three with full dose sorafenib and OSI-906. If we do not observe any significant side effects, then three additional patients will be treated at the same dose level. After confirming the safety of the combination (possibly after first six patietns) the study will proceed with regular accrual. The patients will receive the treatments orally and will be evaluated by physical exam, blood work and imaging. If the cancer is well controlled and the therapy is well tolerated then patients will continue on the trial. If the side effects are significant or the tumor starts to grow or the patients wishes to stop therapy the patient at that time wil be taken off trial.

The trial willl collect blood samples to evalute the level of the investigaitonal agent in the blood. Also samples of the patients tumor will be analyzed to evalute for markers that may predict who benefits from treatment.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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 (See Appendix B)
  • Performance status of 0-2. (See Appendix C)
  • Organ function requirements: hemoglobin > 9.0mg/dl; granulocyte count > 1,000 /mm3 , platelets > 40,000/mm3 , ALT/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.
  • 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- See Appendix D) 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) ('Torsades List' on www.azcert.org/medical-pros/drug-lists/bycategory.cfm, see Appendix E) 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)
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01334710

Locations
United States, Georgia
Emory University Winship Cancer Institute
Atlanta, Georgia, United States, 30322
United States, Michigan
University of Michigan
Ann Arbor, Michigan, United States, 48109
United States, Ohio
Ohio State University
Columbus, Ohio, United States, 43210
Sponsors and Collaborators
Emory University
OSI Pharmaceuticals
Investigators
Principal Investigator: Bassel El-Rayes, MD Emory University Winship Cancer Institute
  More Information

No publications provided

Responsible Party: Bassel El-Rayes, MD, Emory University
ClinicalTrials.gov Identifier: NCT01334710     History of Changes
Other Study ID Numbers: IRB00047003, WCI1887-10
Study First Received: April 6, 2011
Results First Received: September 12, 2012
Last Updated: November 18, 2013
Health Authority: United States: Institutional Review Board
United States: Food and Drug Administration

Keywords provided by Emory University:
Liver cancer

Additional relevant MeSH terms:
Liver Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Liver Diseases
Sorafenib
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on August 18, 2014