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

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ClinicalTrials.gov Identifier: NCT02069145
Recruitment Status : Completed
First Posted : February 24, 2014
Last Update Posted : August 11, 2020
Sponsor:
Information provided by (Responsible Party):
Mereo BioPharma ( OncoMed Pharmaceuticals, Inc. )

Tracking Information
First Submitted Date  ICMJE February 18, 2014
First Posted Date  ICMJE February 24, 2014
Last Update Posted Date August 11, 2020
Study Start Date  ICMJE January 2014
Actual Primary Completion Date May 2017   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: February 19, 2014)
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) ]
The maximum tolerated dose (MTD) will be determined in patients treated with OMP-54F28 in combination with sorafenib in patients with hepatocellular cancer
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: February 19, 2014)
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 ]
Apparent half life, AUC, clearance, volume of distribution
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Dose Escalation Study of OMP-54F28 in Combination With Sorafenib in Patients With Hepatocellular Cancer
Official Title  ICMJE A Phase 1b Dose Escalation Study of OMP-54F28 in Combination With Sorafenib in Patients With Hepatocellular Cancer
Brief Summary 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.
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.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Hepatocellular Cancer
  • Liver Cancer
Intervention  ICMJE Drug: OMP-54F28 with Sorafenib
Other Names:
  • OMP-54F28
  • Sorafenib
Study Arms  ICMJE Experimental: Drug: OMP-54F28, with Sorafenib
Intervention: Drug: OMP-54F28 with Sorafenib
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Estimated Enrollment  ICMJE
 (submitted: February 19, 2014)
10
Original Estimated Enrollment  ICMJE Same as current
Actual Study Completion Date  ICMJE July 2017
Actual Primary Completion Date May 2017   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 90 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02069145
Other Study ID Numbers  ICMJE 54F28-004
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Mereo BioPharma ( OncoMed Pharmaceuticals, Inc. )
Study Sponsor  ICMJE OncoMed Pharmaceuticals, Inc.
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account Mereo BioPharma
Verification Date August 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP