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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01308723
Recruitment Status : Completed
First Posted : March 4, 2011
Last Update Posted : November 2, 2016
Information provided by (Responsible Party):
Hoffmann-La Roche

Brief Summary:
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 or disease Intervention/treatment Phase
Carcinoma, Hepatocellular Drug: RO5323441 Drug: sorafenib Phase 1

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 6 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (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
Study Start Date : March 2011
Actual Primary Completion Date : January 2012
Actual Study Completion Date : January 2012

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
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

Primary Outcome Measures :
  1. Part I : Safety/dose-limiting toxicity: Incidence of adverse events [ Time Frame: up to 12 months ]
  2. Part I: Determination of recommended Part II dose [ Time Frame: up to 12 months ]
  3. Part II: Safety/tolerability: Incidence of adverse events [ Time Frame: up to 28 months ]

Secondary Outcome Measures :
  1. Pharmacokinetics of RO5323441 in combination with sorafenib [ Time Frame: up to 40 months ]
  2. Pharmacokinetics of sorafenib in combination with RO5323441 [ Time Frame: up to 12 months ]
  3. Pharmacodynamic biomarkers (DCE-Magnetic Resonance Imaging evaluations, Placental Growth Factor, Vascular Endothelial Growth Factor Receptors) [ Time Frame: up to 40 months ]
  4. Efficacy: tumor assessments by Magnetic Resonance Imaging or Computed Tomography according to RECIST criteria [ Time Frame: up to 40 months ]
  5. Impact on wound healing (skin biopsies) [ Time Frame: up to 40 months ]
  6. Safety: additional anti-drug antibodies sampling after termination of study drug treatment [ Time Frame: 2 and 4 months after last dose of study drug ]

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Ages Eligible for Study:   21 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01308723

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

Responsible Party: Hoffmann-La Roche Identifier: NCT01308723     History of Changes
Other Study ID Numbers: BP25497
First Posted: March 4, 2011    Key Record Dates
Last Update Posted: November 2, 2016
Last Verified: November 2016

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