NCT01308723

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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
6

participants targeted

Target at below P25 for phase_1

Timeline
Completed

Started Mar 2011

Geographic Reach
1 country

2 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

March 1, 2011

Completed
1 day until next milestone

First Submitted

Initial submission to the registry

March 2, 2011

Completed
2 days until next milestone

First Posted

Study publicly available on registry

March 4, 2011

Completed
10 months until next milestone

Primary Completion

Last participant's last visit for primary outcome

January 1, 2012

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

January 1, 2012

Completed
Last Updated

November 2, 2016

Status Verified

November 1, 2016

Enrollment Period

10 months

First QC Date

March 2, 2011

Last Update Submit

November 1, 2016

Conditions

Carcinoma, Hepatocellular

Outcome Measures

Primary Outcomes (3)

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

    up to 12 months

  • Part I: Determination of recommended Part II dose

    up to 12 months

  • Part II: Safety/tolerability: Incidence of adverse events

    up to 28 months

Secondary Outcomes (6)

  • Pharmacokinetics of RO5323441 in combination with sorafenib

    up to 40 months

  • Pharmacokinetics of sorafenib in combination with RO5323441

    up to 12 months

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

    up to 40 months

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

    up to 40 months

  • Impact on wound healing (skin biopsies)

    up to 40 months

  • +1 more secondary outcomes

Study Arms (3)

Part I

EXPERIMENTAL
Drug: RO5323441Drug: sorafenib

Part II (A)

EXPERIMENTAL
Drug: RO5323441Drug: sorafenib

Part II (B)

ACTIVE COMPARATOR
Drug: sorafenib

Interventions

RO5323441DRUG

escalating doses iv

Part I
sorafenibDRUG

400 mg orally twice daily to once every other day

Part IPart II (A)Part II (B)

Eligibility Criteria

Age21 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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

You may not qualify if:

  • 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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (2)

Unknown Facility

Singapore, 119228, Singapore

Location

Unknown Facility

Singapore, 169610, Singapore

Location

MeSH Terms

Conditions

Carcinoma, Hepatocellular

Interventions

TB-403Sorafenib

Condition Hierarchy (Ancestors)

AdenocarcinomaCarcinomaNeoplasms, Glandular and EpithelialNeoplasms by Histologic TypeNeoplasmsLiver NeoplasmsDigestive System NeoplasmsNeoplasms by SiteDigestive System DiseasesLiver Diseases

Intervention Hierarchy (Ancestors)

Phenylurea CompoundsUreaAmidesOrganic ChemicalsBenzene DerivativesHydrocarbons, AromaticHydrocarbons, CyclicHydrocarbonsNiacinamideNicotinic AcidsAcids, HeterocyclicHeterocyclic CompoundsPyridinesHeterocyclic Compounds, 1-Ring

Study Officials

  • Clinical Trials

    Hoffmann-La Roche

    STUDY DIRECTOR

Study Design

Study Type
interventional
Phase
phase 1
Allocation
RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

March 2, 2011

First Posted

March 4, 2011

Study Start

March 1, 2011

Primary Completion

January 1, 2012

Study Completion

January 1, 2012

Last Updated

November 2, 2016

Record last verified: 2016-11

Locations

SG(2)