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

NCT01737827 | Terminated Phase 2 Results

• 1 other identifier: CINC280X2201
• Study Type: interventional
• Target: 38
• Locations: 4 countries
• Sites: 8

Brief Summary

This study is to find out if INC280 is safe and has beneficial effects in patients with advanced hepatocellular carcinoma known to have dysregulation of c-MET pathway.

Conditions

Advanced Hepatocellular Carcinoma With c-MET Dysregulation

Keywords

INC280; capmatinib; advanced hepatocellular carcinoma; c-MET pathway dysregulation

Outcome Measures

Primary Outcomes (1)

• Time to Progression (TTP) by Investigator Assessment Per RECIST v1.1

  TTP is defined as the time from the date of treatment start to the date of the first documented radiological confirmation of disease progression or death due to underlying cancer. Tumor response was based on investigator assessment per Response Evaluation Criteria In Solid Tumors (RECIST) v1.1. For RECIST v1.1, Progressive disease (PD) = At least a 20% increase in the sum of diameters of all measured target lesions, taking as reference the smallest sum of diameter of all target lesions recorded at or after baseline. In addition, the sum must also demonstrate an absolute increase of at least 5 mm. If a patient had not had the event at the date of analysis cut-off or when he/she received any further anti-neoplastic therapy, TTP was censored at the time of the last adequate assessment. TTP was estimated using the Kaplan-Meier method.

  Up to approximately 8 years and 2 months

Secondary Outcomes (13)

• Overall Response Rate (ORR) by Investigator Assessment Per RECIST 1.1

  Up to approximately 8 years and 2 months

• Disease Control Rate (DCR) by Investigator Assessment Per RECIST 1.1

  Up to approximately 8 years and 2 months

• Progression-Free Survival (PFS) by Investigator Assessment Per RECIST 1.1

  Up to approximately 8 years and 2 months

• Overall Survival (OS)

  Up to approximately 8 years and 2 months

• Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)

  From first dose of study drug to 30 days after last dose, up to approximately 8 years and 2 months

Study Arms (1)

INC280

EXPERIMENTAL

The protocol consisted of two independent parts (Dose-Determining Part and Dose Expansion Part). Patients were treated with INC280 300 mg twice a day in the Dose-Determining Part. The dose for the Expansion Part could be lower, equal or higher than in the Dose-Determining Part and was determined after the Dose Determining Part at the dose decision analysis.

Drug: INC280

Interventions

INC280 DRUG

INC280 was administered orally on a continuous twice a day (BID) dosing schedule, from Day 1 until Day 21 of each 21-day cycle. INC280 was initially supplied as hard gelatin capsules and subsequently also as film-coated tablets.

Also known as: capmatinib

INC280

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.
• Advanced hepatocellular carcinoma which could not be suitable for treatment with locoregional therapies or has progressed following locoregional therapy.
• Measurable disease as determined by RECIST version 1.1.
• Current cirrhotic status of Child-Pugh class A with no encephalopathy.
• Eastern Cooperative Oncology Group (ECOG) performance status \< or = 2.

You may not qualify if:

• Received any prior systemic chemotherapy or molecular-targeted therapy for hepatocellular carcinoma such as sorafenib.
• Previous treatment with c-MET inhibitor or hepatocyte growth factor targeting therapy.
• Previous local therapy completed less than 4 weeks prior to dosing and, if present, any acute toxicity \> grade 1.
• Known active bleeding (e.g. bleeding from gastro-intestinal ulcers or esophageal varices) within 2 months prior to screening or with history or evidence of inherited bleeding diathesis or coagulopathy.
• Clinically significant venous or arterial thrombotic disease within past 6 months.
• History of acute or chronic pancreatitis, surgery of pancreas or any risk factors that may increase risk of pancreatitis.

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (8)

Novartis Investigative Site

Nanjing, Jiangsu, 210002, China

Location

Novartis Investigative Site

Xi’an, Shanxi, 710032, China

Location

Novartis Investigative Site

Hangzhou, Zhejiang, 310016, China

Location

Novartis Investigative Site

Hong Kong, Hong Kong

Location

Novartis Investigative Site

Singapore, 168583, Singapore

Location

Novartis Investigative Site

Khon Kaen, THA, 40002, Thailand

Location

Novartis Investigative Site

Bangkok, 10330, Thailand

Location

Novartis Investigative Site

Bangkok, 10700, Thailand

Location

Related Publications (1)

• Qin S, Chan SL, Sukeepaisarnjaroen W, Han G, Choo SP, Sriuranpong V, Pan H, Yau T, Guo Y, Chen M, Ren Z, Xu J, Yen CJ, Lin ZZ, Manenti L, Gu Y, Sun Y, Tiedt R, Hao L, Song W, Tanwandee T. A phase II study of the efficacy and safety of the MET inhibitor capmatinib (INC280) in patients with advanced hepatocellular carcinoma. Ther Adv Med Oncol. 2019 Dec 11;11:1758835919889001. doi: 10.1177/1758835919889001. eCollection 2019.

  PMID: 31853265 DERIVED

MeSH Terms

Interventions

capmatinib

Results Point of Contact

• Title: Study Director
• Organization: Novartis Pharmaceuticals

Novartis.email@novartis.com

862-778-8300

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 12, 2012
• First Posted: November 30, 2012
• Study Start: March 25, 2013
• Primary Completion: April 24, 2023
• Study Completion: May 24, 2023
• Last Updated: September 24, 2024
• Results First Posted: September 24, 2024

Record last verified: 2024-09

Data Sharing

• IPD Sharing: Will share

Locations

HK (1); SG (1); CN (3); TH (3)