Study of Efficacy and Safety INC280 in Patients With Advanced Hepatocellular Carcinoma

NCT01964235 | Withdrawn Phase 2 DMC

• 1 other identifier: CINC280X2203
• Study Type: interventional
• Target: N/A
• Locations: 7 countries
• Sites: 15

Brief Summary

This study is establish whether INC280 is safe and has beneficial effects in patients with advanced hepatocellular carcinoma known to have dysregulation of c-MET pathway and whose disease progressed while on, or after, treatment with sorafenib or who are intolerant to sorafenib. Patients will be randomized in a 2:1 ratio to receive INC280 at 600mg BID plus best supportive care (BSC) or placebo plus BSC, until disease progression or intolerable to study treatment. Patients treated with placebo plus BSC will have the opportunity to receive INC280 treatment upon documented further disease progression (RECIST 1.1) per investigator's discretion after unblinding. Patient will be stratified to geographical region (Asia vs Rest of World ) and tumor burden (present macroscopic vascular invasion and/or extra-hepatic spread vs not present).

Conditions

Advanced Hepatocellular Carcinoma

Keywords

INC280, advanced hepatocellular carcinoma, c-MET pathway dysregulation.

Outcome Measures

Primary Outcomes (1)

• Time to progression using Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1

  Time to progression is the time from the date of baseline evaluation to the date of the first documented radiological confirmation of disease progression.

  baseline, 6 weeks up to 6 months

Secondary Outcomes (8)

• Best Overall Response

  date of treatment, every 6 weeks up to 6 months

• Overall Response Rate

  baseline, every 6 weeks up to 6 months

• Disease Control Rate

  baseline, every 6 weeks up to 6 months

• Progression Free Survival

  randomization, every 6 weeks up to 6 months

• Overall Survival

  randomization until death, average 10 months

Study Arms (2)

INC280 plus best supportive care

EXPERIMENTAL

Approximately 46 patients will be treated with INC280 600 mg twice a day plus best supportive care.

Drug: INC280

Placebo plus best supportive care

PLACEBO COMPARATOR

Approximately 23 patients will be treated with matching placebo twice a day plus best supportive care.

Drug: Placebo

Interventions

INC280 DRUG

INC280 will be administered orally and continuously on a twice a day dosing schedule.

INC280 plus best supportive care

Placebo DRUG

Placebo will be administered orally and continuously on a twice a day dosing schedule.

Placebo plus best supportive care

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Confirmed c-MET pathway dysregulation.- Hepatocellular carcinoma stage B or C according to the Barcelona Clinic Liver cancer staging classification. - Current cirrhotic status of Child-Pugh class A with no encephalopathy. - Documented disease progression during or after discontinuation of sorafenib treatment or intolerance to sorafenib treatment. - Measurable disease as determined by RECIST v1.1. - ECOG performance status ≤ 1

You may not qualify if:

• Previous local antineoplastic therapy or investigational drug completed less than 5 half-lives of the agent prior to randomization and have not recovered from clinically significant toxicity from such treatment to grade ≤1 by the NCI-CTCAE. - Received any targeted therapy other than sorafenib.
• Active bleeding within 28 days prior to screening visit including variceal bleeding (esophageal varices should be treated according to standard practice and procedure completed 28 days prior to screening visit). - Clinically significant venous or arterial thrombotic disease within past 6 months.

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (15)

Massachusetts General Hospital Mass General Hospital

Boston, Massachusetts, 02115, United States

Location

Research Medical Center Onc Dept

Kansas City, Missouri, 64132, United States

Location

Novartis Investigative Site

Kogarah, New South Wales, 2217, Australia

Location

Novartis Investigative Site

Heidelberg, Victoria, 3084, Australia

Location

Novartis Investigative Site

Clichy, 92110, France

Location

Novartis Investigative Site

Lille, 59037, France

Location

Novartis Investigative Site

Montpellier, 34298, France

Location

Novartis Investigative Site

Nice, 06202, France

Location

Novartis Investigative Site

Essen, 45147, Germany

Location

Novartis Investigative Site

Würzburg, 97080, Germany

Location

Novartis Investigative Site

Hong Kong, Hong Kong

Location

Novartis Investigative Site

Hong Kong SAR, Hong Kong

Location

Novartis Investigative Site

Córdoba, Andalusia, 14004, Spain

Location

Novartis Investigative Site

Bern, 3010, Switzerland

Location

Novartis Investigative Site

Geneva, 1211, Switzerland

Location

MeSH Terms

Interventions

capmatinib

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 14, 2013
• First Posted: October 17, 2013
• Study Start: December 1, 2016
• Primary Completion: July 1, 2019
• Study Completion: July 1, 2019
• Last Updated: September 1, 2016

Record last verified: 2016-08

Locations

DE (2); ES (1); CH (2); HK (2); US (2); AU (2); FR (4)