A Dose-Finding and Exploratory Study of RO5323441 in Combination With Sorafenib in Patients With Hepatocellular Carcinoma

This study has been completed.
Information provided by (Responsible Party):
Hoffmann-La Roche
ClinicalTrials.gov Identifier:
First received: March 2, 2011
Last updated: May 4, 2016
Last verified: May 2016
This open-label study will assess the safety, efficacy and pharmacokinetics of RO5323441 in combination with sorafenib in patients with advanced or metastatic hepatocellular carcinoma previously untreated with systemic therapy. In the dose-finding Part I, cohorts of patients will receive escalating doses of RO5323441 intravenously (iv) every 2 weeks in combination with sorafenib 400 mg orally twice daily. In the exploratory Part II, patients will be randomized to receive either the previously established dose of RO5323441 iv every 2 weeks plus continuous oral sorafenib or sorafenib alone. Anticipated time on study treatment is until disease progression or unacceptable toxicity occurs. For patients in the sorafenib arm with disease progression crossover to combination treatment with RO5323441 will be allowed.

Condition Intervention Phase
Carcinoma, Hepatocellular
Drug: RO5323441
Drug: sorafenib
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacokinetics/Dynamics Study
Masking: Open Label
Primary Purpose: Treatment
Official Title: Exploratory Open Label Dose-escalation Phase Ib Study to Evaluate Safety, Pharmacokinetics and Therapeutic Activity of RO5323441, Administered Intravenously, in Combination With Sorafenib (Nexavar®), in Patients With Advanced or Metastatic and/or Unresectable Hepatocellular Carcinoma

Resource links provided by NLM:

Further study details as provided by Hoffmann-La Roche:

Primary Outcome Measures:
  • Part I : Safety/dose-limiting toxicity: Incidence of adverse events [ Time Frame: up to 12 months ] [ Designated as safety issue: No ]
  • Part I: Determination of recommended Part II dose [ Time Frame: up to 12 months ] [ Designated as safety issue: No ]
  • Part II: Safety/tolerability: Incidence of adverse events [ Time Frame: up to 28 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Pharmacokinetics of RO5323441 in combination with sorafenib [ Time Frame: up to 40 months ] [ Designated as safety issue: No ]
  • Pharmacokinetics of sorafenib in combination with RO5323441 [ Time Frame: up to 12 months ] [ Designated as safety issue: No ]
  • Pharmacodynamic biomarkers (DCE-Magnetic Resonance Imaging evaluations, Placental Growth Factor, Vascular Endothelial Growth Factor Receptors) [ Time Frame: up to 40 months ] [ Designated as safety issue: No ]
  • Efficacy: tumor assessments by Magnetic Resonance Imaging or Computed Tomography according to RECIST criteria [ Time Frame: up to 40 months ] [ Designated as safety issue: No ]
  • Impact on wound healing (skin biopsies) [ Time Frame: up to 40 months ] [ Designated as safety issue: No ]
  • Safety: additional anti-drug antibodies sampling after termination of study drug treatment [ Time Frame: 2 and 4 months after last dose of study drug ] [ Designated as safety issue: No ]

Enrollment: 6
Study Start Date: March 2011
Study Completion Date: January 2012
Primary Completion Date: January 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Part I Drug: RO5323441
escalating doses iv
Drug: sorafenib
400 mg orally twice daily to once every other day
Experimental: Part II (A) Drug: RO5323441
iv every 2 weeks
Drug: sorafenib
400 mg orally twice daily to once every other day
Active Comparator: Part II (B) Drug: sorafenib
400 mg orally twice daily to once every other day


Ages Eligible for Study:   21 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Adult patients >/= 21 years of age
  • Advanced or metastatic and/or unresectable hepatocellular carcinoma
  • At least 1 measurable lesion according to RECIST criteria
  • Primary tumor in situ (Expansion Cohort Part I, Part II)
  • Eastern Cooperative Oncology Group (ECOG) performance status 0-1
  • Adequate bone marrow, liver and renal function

Exclusion Criteria:

  • Prior systemic treatment for metastatic hepatocellular carcinoma or patients who had tumor removed (Expansion Cohort Part I, Part II)
  • Major surgery within previous 4 weeks or planned major surgical procedure during course of study
  • Radiation therapy within 28 days prior to start of study treatment
  • Serious non-healing wound, ulcer ore bone fracture
  • History of uncontrolled seizures or encephalopathy within the last 6 months
  • Current central nervous system (CNS) metastases or spinal cord compression
  • History of gastrointestinal perforation or esophageal/gastric bleeding within 6 months prior to study enrollment
  • History of another primary malignancy and off treatment for </= 3 years, except for non-melanoma skin cancer and carcinoma in situ of the cervix
  • Patients with prior liver transplant
  • Inadequately controlled hypertension or prior history of hypertensive crisis or hypertensive encephalopathy
  • Active bleeding diathesis
  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: NCT01308723

Singapore, Singapore, 119228
Singapore, Singapore, 169610
Sponsors and Collaborators
Hoffmann-La Roche
Study Director: Clinical Trials Hoffmann-La Roche
  More Information

Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT01308723     History of Changes
Other Study ID Numbers: BP25497 
Study First Received: March 2, 2011
Last Updated: May 4, 2016
Health Authority: Singapore: Ministry of Health

Additional relevant MeSH terms:
Carcinoma, Hepatocellular
Digestive System Diseases
Digestive System Neoplasms
Liver Diseases
Liver Neoplasms
Neoplasms by Histologic Type
Neoplasms by Site
Neoplasms, Glandular and Epithelial
Antibodies, Monoclonal
Antineoplastic Agents
Enzyme Inhibitors
Immunologic Factors
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs
Protein Kinase Inhibitors

ClinicalTrials.gov processed this record on May 26, 2016