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

Carcinoma, Hepatocellular Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01308723
• Other study ID #: BP25497
• Status: Completed
• Phase: Phase 1
• First received: March 2, 2011
• Last updated: November 1, 2016
• Start date: March 2011
• Est. completion date: January 2012

Study information

• Verified date: November 2016
• Source: Hoffmann-La Roche
• Contact: n/a
• Is FDA regulated: No
• Health authority: Singapore: Ministry of Health
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 6
• Est. completion date: January 2012
• Est. primary completion date: January 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 21 Years and older

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Pharmacokinetics/Dynamics Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Hepatocellular

Intervention

Drug:
• RO5323441
escalating doses iv
• RO5323441
iv every 2 weeks
• sorafenib
400 mg orally twice daily to once every other day

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Hoffmann-La Roche

Country where clinical trial is conducted

Singapore, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Part I : Safety/dose-limiting toxicity: Incidence of adverse events		up to 12 months	No
Primary	Part I: Determination of recommended Part II dose		up to 12 months	No
Primary	Part II: Safety/tolerability: Incidence of adverse events		up to 28 months	No
Secondary	Pharmacokinetics of RO5323441 in combination with sorafenib		up to 40 months	No
Secondary	Pharmacokinetics of sorafenib in combination with RO5323441		up to 12 months	No
Secondary	Pharmacodynamic biomarkers (DCE-Magnetic Resonance Imaging evaluations, Placental Growth Factor, Vascular Endothelial Growth Factor Receptors)		up to 40 months	No
Secondary	Efficacy: tumor assessments by Magnetic Resonance Imaging or Computed Tomography according to RECIST criteria		up to 40 months	No
Secondary	Impact on wound healing (skin biopsies)		up to 40 months	No
Secondary	Safety: additional anti-drug antibodies sampling after termination of study drug treatment		2 and 4 months after last dose of study drug	No