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

• Sponsor: Novartis Pharmaceuticals (Industry)
• Overall Status: Withdrawn
• CT.gov ID: NCT01964235
• Collaborator: (none)
• Enrollment: 0
• Locations: 15
• Arms: 2
• Duration (Months): 30.9
• Patients Per Site: 0
• Patients Per Site Per Month: 0

Study Details

Study Description

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).

Condition or Disease	Intervention/Treatment	Phase
Advanced Hepatocellular Carcinoma	Drug: INC280; Drug: Placebo	Phase 2

Detailed Description

Study was cancelled by Sponsor prior to enrollment of patients.

Study Design

• Study Type: Interventional
• Actual Enrollment: 0 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Randomized Phase II, Double-blind, Placebo-controlled, Multi-center Study to Evaluate the Efficacy and Safety of INC280 in Adult Patients With Advanced Hepatocellular Carcinoma After Progression or Intolerance to Sorafenib Treatment
• Study Start Date: Dec 1, 2016
• Anticipated Primary Completion Date: Jul 1, 2019
• Anticipated Study Completion Date: Jul 1, 2019

Arms and Interventions

Arm	Intervention/Treatment
Experimental: INC280 plus best supportive care Approximately 46 patients will be treated with INC280 600 mg twice a day plus best supportive care.	Drug: INC280; INC280 will be administered orally and continuously on a twice a day dosing schedule.
Placebo Comparator: Placebo plus best supportive care Approximately 23 patients will be treated with matching placebo twice a day plus best supportive care.	Drug: Placebo; Placebo will be administered orally and continuously on a twice a day dosing schedule.

Outcome Measures

Primary Outcome Measures

1. Time to progression using Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1 [baseline, 6 weeks up to 6 months]

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

Secondary Outcome Measures

1. Best Overall Response [date of treatment, every 6 weeks up to 6 months]

   Best overall response is defined as the best response recorded from the date of randomization until the date of last tumor assessment per RECIST version 1.1.

2. Overall Response Rate [baseline, every 6 weeks up to 6 months]

   Overall Response Rate is defined as the proportion of patients with a best overall response of complete response or partial response at any time on study per RECIST version 1.1.

3. Disease Control Rate [baseline, every 6 weeks up to 6 months]

   Disease control rate is defined as the proportion of patients with a best overall response of complete response, partial response or stable disease at any time on study per RECIST version 1.1.

4. Progression Free Survival [randomization, every 6 weeks up to 6 months]

   Progression free survival is defined as the time from date of randomization to the date of the first radiologically documented progression or death due to any cause. If a patient has not experienced radiologically documented progression or death, progression free survival is censored at the date of last adequate tumor assessment.

5. Overall Survival [randomization until death, average 10 months]

   Overall survival is defined as the time from date of randomization to the date of death due to any cause. If a patient is not known to have died, survival will be censored at the date of last contact.

6. Safety: adverse events, serious adverse events [From baseline until 30 days post study treatment]

   Frequency, duration and severity of adverse events.

7. Safety: hematology and chemistry values, vital signs, electrocardiograms [From baseline until end of treatment, average 6 months from baseline]

   Change from baseline values.

8. Tolerability of study drug [From date of randomization until end of treatment, average 6 months from baseline]

   Tolerability will be assessed by summarizing the number of dose interruptions, dose reductions and dose intensity.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• 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

Exclusion Criteria:

• 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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Massachusetts General Hospital Mass General Hospital	Boston	Massachusetts	United States	02115
2	Research Medical Center Onc Dept	Kansas City	Missouri	United States	64132
3	Novartis Investigative Site	Kogarah	New South Wales	Australia	2217
4	Novartis Investigative Site	Heidelberg	Victoria	Australia	3084
5	Novartis Investigative Site	Clichy		France	92110
6	Novartis Investigative Site	LILLE Cedex		France	59037
7	Novartis Investigative Site	Montpellier Cedex 5		France	34298
8	Novartis Investigative Site	Nice Cedex 3		France	06202
9	Novartis Investigative Site	Essen		Germany	45147
10	Novartis Investigative Site	Würzburg		Germany	97080
11	Novartis Investigative Site	Hong Kong SAR		Hong Kong
12	Novartis Investigative Site	Hong Kong		Hong Kong
13	Novartis Investigative Site	Cordoba	Andalucia	Spain	14004
14	Novartis Investigative Site	Bern		Switzerland	3010
15	Novartis Investigative Site	Genève		Switzerland	1211

Sponsors and Collaborators

• Novartis Pharmaceuticals

Investigators

• Study Director: Novartis Pharmaceuticals, Novartis Pharmaceuticals

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Novartis Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT01964235
• Other Study ID Numbers: CINC280X2203
• First Posted: Oct 17, 2013
• Last Update Posted: Sep 1, 2016
• Last Verified: Aug 1, 2016

• Keywords provided by Novartis Pharmaceuticals: INC280, advanced hepatocellular carcinoma, c-MET pathway dysregulation.
• Additional relevant MeSH terms: Carcinoma; Carcinoma, Hepatocellular

Study Results

No Results Posted as of Sep 1, 2016