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Dose Escalation Study of OMP-54F28 in Combination With Sorafenib in Patients With Hepatocellular Cancer

This study is currently recruiting participants. (see Contacts and Locations)
Verified May 2014 by OncoMed Pharmaceuticals, Inc.
Sponsor:
Information provided by (Responsible Party):
OncoMed Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier:
NCT02069145
First received: February 18, 2014
Last updated: May 7, 2014
Last verified: May 2014
  Purpose

This is an open-label Phase 1b dose-escalation study to assess the safety, tolerability, and PK of OMP-54F28 when combined with sorafenib. OMP-54F28 will be administered IV on Day 1 of each 21-day cycle. The planned dose levels of OMP-54F28 are 5 and 10 mg/kg. Depending on safety in this study, additional lower or intermediate dose levels may be evaluated.


Condition Intervention Phase
Hepatocellular Cancer
Liver Cancer
Drug: OMP-54F28 with Sorafenib
Phase 1

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 1b Dose Escalation Study of OMP-54F28 in Combination With Sorafenib in Patients With Hepatocellular Cancer

Resource links provided by NLM:


Further study details as provided by OncoMed Pharmaceuticals, Inc.:

Primary Outcome Measures:
  • Safety and tolerability of OMP-54F28 in combination with sorafenib in patients with hepatocellular cancer [ Time Frame: Subjects will be treated and observed for DLT through the end of the first cycle (from Day 0 - 21) ] [ Designated as safety issue: Yes ]
    The maximum tolerated dose (MTD) will be determined in patients treated with OMP-54F28 in combination with sorafenib in patients with hepatocellular cancer


Secondary Outcome Measures:
  • Pharmacokinetics (PK) of OMP-54F28 and sorafenib when administered in combination to patients with hepatocellular cancer [ Time Frame: OMP-54F28 will be administered IV on Day 1 of each 21 day cycle. Plasma sample for Parmacokinetics (PK) analysis to be obtained at various time points, 30 minutes after end of OMP-54F28 infusion and before sorafenib treatment ] [ Designated as safety issue: No ]
    Apparent half life, AUC, clearance, volume of distribution


Estimated Enrollment: 10
Study Start Date: January 2014
Estimated Study Completion Date: January 2016
Estimated Primary Completion Date: August 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Drug: OMP-54F28, with Sorafenib Drug: OMP-54F28 with Sorafenib
Other Names:
  • OMP-54F28
  • Sorafenib

Detailed Description:

Depending on emerging safety data from the Phase 1a study 54F28-001 with continuing dose escalation, additional higher dose levels of OMP-54F28 may be evaluated in this study. Alternative dosing schedules of OMP-54F28 may be explored based on emerging nonclinical and clinical data for safety, PD, PK and efficacy. The starting dose for a new dosing schedule will be chosen to result in an AUC equivalent to the highest dose level that cleared on the previously studied dosing schedule. No dose escalation of OMP-54F28 will be allowed within a dose cohort. Sorafenib 400 mg will be given orally twice daily (PO BID). Sorafenib dosing schedules with a total daily dose <800 mg (e.g. Sorafenib 400 mg once daily) may be evaluated in this study depending on emerging safety data from this study.

  Eligibility

Ages Eligible for Study:   18 Years to 90 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Signed Informed Consent Form
  • Age ≥18 years
  • Histologically documented hepatocellular carcinoma
  • Locally advanced or metastatic disease
  • Availability of FFPE tumor tissue, either archival or obtained at study entry through fresh biopsy

    o Tumor tissue from fine needle aspiration is not acceptable.

  • ECOG performance status of 0 or 1 (see Appendix C)
  • All acute treatment-related toxicity from prior therapy must have resolved to Grade ≤ 1 prior to study entry
  • Adequate hematologic and end-organ function
  • Child-Pugh Classification A (see Appendix D)
  • Evaluable or measurable disease per RECIST v1.1
  • For women of childbearing potential and men with partners of childbearing potential, agreement to use two effective forms of contraception

Exclusion Criteria:

  • Inability to take oral medications
  • Prior systemic therapy for locally advanced or metastatic hepatocellular cancer
  • Prior adjuvant therapy with sorafenib or another Raf/VEGF inhibitor
  • Prior history of allografts, including, but not limited to, liver and bone marrow transplants
  • Esophageal or gastric variceal bleeding within last 3 months
  • Risk for varices, based on known history of esophageal or gastric varices, evidence of hepatic cirrhosis and/or portal hypertension including biopsy-proven cirrhosis, hypersplenism, or radiographic findings of varices
  • Clinically evident ascites
  • Evidence of encephalopathy within last 3 months
  • Treatment with inducers of cytochrome P450 3A4 (CYP3A4) within 7 days prior to first dose of study treatment
  • Treatment with interferon within 4 weeks prior to first dose of study treatment
  • Treatment with any anti-cancer therapy, including radiotherapy, chemotherapy, biologic therapy, or herbal therapy within 3 weeks or 5 half-lives (for systemic agents), whichever is shorter
  • Known hypersensitivity to any component of study treatments that resulted in drug discontinuation
  • Uncontrolled seizure disorder or active neurologic disease
  • Untreated brain metastases
  • Leptomeningeal disease as a manifestation of cancer
  • Active infection requiring antibiotics
  • Bisphosphonate therapy for symptomatic hypercalcemia
  • Significant intercurrent illness including, but not limited to, unstable angina pectoris, and cardiac arrhythmia, or psychiatric illness/social situation that would limit compliance with study requirements
  • Pregnancy, lactation, or breastfeeding
  • Known HIV infection
  • Active Hepatitis B infection in the absence of adequate antiviral therapy
  • Uncontrolled hypertension, defined as systolic blood pressure >140 mm Hg or diastolic blood pressure >90 mm Hg, despite medical management
  • Pulmonary hemorrhage of Grade ≥2 within 28 days prior to first dose of study treatment
  • Any other hemorrhage or bleeding of Grade ≥3 within 28 days prior to first dose of study treatment
  • Evidence of bleeding diathesis or significant coagulopathy (in the absence of therapeutic anticoagulation)
  • Concurrent use of therapeutic warfarin
  • New York Heart Association Classification III or IV (see Appendix F)
  • Congenital long QT syndrome
  • Known clinically significant gastrointestinal disease including, but not limited to, inflammatory bowel disease
  • Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to the first dose of study treatment or anticipation of need for major surgical procedure during the course of the study
  • Osteoporosis based on a T-score of <-2.5 at the left or right total hip, left or right femoral neck or lumbar spine (L1-L4) as determined by DEXA scan
  • Bone metastases and one of the following:

    • Prior history of a pathologic fracture
    • Lytic lesion requiring an impending orthopedic intervention
    • Lack of treatment with a bisphosphonate or denosumab
  • Treatment with a thiazolidinedione PPAR gamma inhibitor; e.g. Actos® (pioglitazone) and Avandia® (rosiglitzone)
  • Active treatment with an oral or IV glucocortocoid for ≥4 weeks at a daily dose equivalent to or greater than 7.5 mg of oral prednisone
  • Fasting β-CTX of >1000 pg/mL
  • Metabolic bone disease, such as hyperparathyroidism, Paget's disease or osteomalacia
  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: NCT02069145

Locations
United States, California
USC/Norris Comprehensive Cancer Center Recruiting
Los Angeles, California, United States, 90033
Contact: Anthony El-Khoueiry, MD    323-865-3967    elkhouei@usc.edu   
Principal Investigator: Anthony El-Khoueiry, M.D.         
United States, Colorado
University of Colorado Cancer Center Recruiting
Aurora, Colorado, United States, 80045
Contact: Thomas Purcell, MD, MBS, CSCS    720-848-8093    tom.purcell@ucdenver.edu   
Principal Investigator: Thomas Purcell, MD, MBA, CSCS         
United States, Indiana
IU Health University Hospital Recruiting
Indianapolis, Indiana, United States, 46202
Contact: Safi Shahda, MD    317-948-6942    shahdas@iu.edu   
Principal Investigator: Safi Shahda, M.D.         
United States, Massachusetts
Massachusetts General Hospital Cancer Center Recruiting
Boston, Massachusetts, United States, 02114
Contact: Andrew Zhu, MD, PhD    617-643-3415    azhu@partners.org   
Principal Investigator: Andrew Zhu, MD, PhD         
United States, New York
Mount Sinai Medical Center Recruiting
New York, New York, United States, 10029
Contact: Celina Ang, MD    212-241-6631    celina.ang@mssm.edu   
Principal Investigator: Celina Ang, MD         
United States, Pennsylvania
Fox Chase Cancer Center Recruiting
Philadelphia, Pennsylvania, United States, 19111
Contact: Crystal Denlinger, MD    215-214-1676    crystal.denlinger@fccc.edu   
Principal Investigator: Crystal Denlinger, MD         
Sponsors and Collaborators
OncoMed Pharmaceuticals, Inc.
  More Information

No publications provided

Responsible Party: OncoMed Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier: NCT02069145     History of Changes
Other Study ID Numbers: 54F28-004
Study First Received: February 18, 2014
Last Updated: May 7, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by OncoMed Pharmaceuticals, Inc.:
Hepatocellular Cancer
Liver Cancer

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

ClinicalTrials.gov processed this record on November 25, 2014