Back to results

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

Primary Purpose

Carcinoma, Hepatocellular

Status

Completed

Phase

Phase 1

Locations

Singapore

Study Type

Interventional

Intervention

RO5323441

sorafenib

About this trial

This is an interventional treatment trial for Carcinoma, Hepatocellular

Eligibility Criteria

21 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Active Comparator

Arm Label

Part I

Part II (A)

Part II (B)

Arm Description

Outcomes

Primary Outcome Measures

Part I : Safety/dose-limiting toxicity: Incidence of adverse events

Part I: Determination of recommended Part II dose

Part II: Safety/tolerability: Incidence of adverse events

Secondary Outcome Measures

Pharmacokinetics of RO5323441 in combination with sorafenib

Pharmacokinetics of sorafenib in combination with RO5323441

Pharmacodynamic biomarkers (DCE-Magnetic Resonance Imaging evaluations, Placental Growth Factor, Vascular Endothelial Growth Factor Receptors)

Efficacy: tumor assessments by Magnetic Resonance Imaging or Computed Tomography according to RECIST criteria

Impact on wound healing (skin biopsies)

Safety: additional anti-drug antibodies sampling after termination of study drug treatment

Full Information

NCT ID

NCT01308723

First Posted

March 2, 2011

Last Updated

November 1, 2016

Sponsor

Hoffmann-La Roche

1. Study Identification

Unique Protocol Identification Number

NCT01308723

Brief Title

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

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 Type

Interventional

2. Study Status

Record Verification Date

November 2016

Overall Recruitment Status

Completed

Study Start Date

March 2011 (undefined)

Primary Completion Date

January 2012 (Actual)

Study Completion Date

January 2012 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Hoffmann-La Roche

4. Oversight

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Carcinoma, Hepatocellular

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

6 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Part I

Arm Type

Experimental

Arm Title

Part II (A)

Arm Type

Experimental

Arm Title

Part II (B)

Arm Type

Active Comparator

Intervention Type

Drug

Intervention Name(s)

RO5323441

Intervention Description

escalating doses iv

Intervention Type

Drug

Intervention Name(s)

RO5323441

Intervention Description

iv every 2 weeks

Intervention Type

Drug

Intervention Name(s)

sorafenib

Intervention Description

400 mg orally twice daily to once every other day

Primary Outcome Measure Information:

Title

Part I : Safety/dose-limiting toxicity: Incidence of adverse events

Time Frame

up to 12 months

Title

Part I: Determination of recommended Part II dose

Time Frame

up to 12 months

Title

Part II: Safety/tolerability: Incidence of adverse events

Time Frame

up to 28 months

Secondary Outcome Measure Information:

Title

Pharmacokinetics of RO5323441 in combination with sorafenib

Time Frame

up to 40 months

Title

Pharmacokinetics of sorafenib in combination with RO5323441

Time Frame

up to 12 months

Title

Pharmacodynamic biomarkers (DCE-Magnetic Resonance Imaging evaluations, Placental Growth Factor, Vascular Endothelial Growth Factor Receptors)

Time Frame

up to 40 months

Title

Efficacy: tumor assessments by Magnetic Resonance Imaging or Computed Tomography according to RECIST criteria

Time Frame

up to 40 months

Title

Impact on wound healing (skin biopsies)

Time Frame

up to 40 months

Title

Safety: additional anti-drug antibodies sampling after termination of study drug treatment

Time Frame

2 and 4 months after last dose of study drug

10. Eligibility

Sex

All

Minimum Age & Unit of Time

21 Years

Accepts Healthy Volunteers

Eligibility Criteria

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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Clinical Trials

Organizational Affiliation

Hoffmann-La Roche

Official's Role

Study Director

Facility Information:

City

Singapore

ZIP/Postal Code

119228

Country

Singapore

City

Singapore

ZIP/Postal Code

169610

Country

Singapore

12. IPD Sharing Statement

Learn more about this trial

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

We'll reach out to this number within 24 hrs