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

This study is ongoing, but not recruiting participants.
Sponsor:
ClinicalTrials.gov Identifier:
NCT01737827
First Posted: November 30, 2012
Last Update Posted: August 10, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
  Purpose
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.

Condition Intervention Phase
Advanced Hepatocellular Carcinoma With c-MET Dysregulation Drug: INC280 Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase II, Open Label, Single Arm, Multicenter Study of INC280 Administered Orally in Adults With Advanced Hepatocellular Carcinoma

Further study details as provided by Novartis ( Novartis Pharmaceuticals ):

Primary Outcome Measures:
  • Time to progression using Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1 [ Time Frame: 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 or death due to underlying cancer.


Secondary Outcome Measures:
  • Overall Response Rate [ Time Frame: 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.

  • Progression free survival [ Time Frame: date of treatment, every 6 weeks up to 6 months ]
    Progression free survival is defined as the time from date of first study treatment intake to the date of the first radiologically documented progression or death due to any cause or initiation of new antineoplastic therapy. if a patient has not had an event, progression free survival is censored at the date of last adequate tumor assessment.

  • Overall survival [ Time Frame: From date of treatment until death, average 10.7 months ]
    Overall survival is defined as the time from date of first study treatment intake 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.

  • Disease Control Rate [ Time Frame: 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

  • Safety: adverse events, serious adverse events [ Time Frame: From baseline until 30 days post study treatment ]
    Frequency, duration and severity of adverse events.

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

  • Tolerability of study drug [ Time Frame: From date start of treatment 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.

  • Plasma pharmacokinetic parameter: AUC0-t [ Time Frame: Days 1, 2, 15 and 16 of Cycle 1, Day 1 of Cycle 2 and Cycle 3 ]
    Plasma concentration of INC280 versus time profiles. AUC=Area Under the Curve

  • Alpha-fetoprotein [ Time Frame: baseline, every 6 weeks up to 6 months ]
    Change from baseline

  • Soluble c-MET [ Time Frame: baseline, Cycle 1 Days 1, 2 and 15, then Day 1 of each cycle until end of treatment ]
    Change from baseline

  • Soluble Hepatocyte Growth Factor [ Time Frame: baseline, Cycle 1 Days 1, 2 and 15, then Day 1 of each cycle until end of treatment ]
    Change from baseline

  • Plasma pharmacokinetic parameter: CL/F [ Time Frame: Days 1, 2, 15 and 16 of Cycle 1, Day 1 of Cycle 2 and Cycle 3 ]
    Plasma concentration of INC280 versus time profiles

  • Plasma pharmacokinetic parameter: Cmax [ Time Frame: Days 1, 2, 15 and 16 of Cycle 1, Day 1 of Cycle 2 and Cycle 3 ]
    Plasma concentration of INC280 versus time profiles. Cmax = Maximum concentration

  • Plasma pharmacokinetic parameter: Tmax [ Time Frame: Days 1, 2, 15 and 16 of Cycle 1, Day 1 of Cycle 2 and Cycle 3 ]
    Plasma concentration of INC280 versus time profiles. Tmax =Time to reach maximum concentration

  • Plasma pharmacokinetic parameter: T1/2 [ Time Frame: Days 1, 2, 15 and 16 of Cycle 1, Day 1 of Cycle 2 and Cycle 3 ]
    Plasma concentration of INC280 versus time profiles

  • Plasma pharmacokinetic parameter: Racc [ Time Frame: Days 1, 2, 15 and 16 of Cycle 1, Day 1 of Cycle 2 and Cycle 3 ]
    Plasma concentration of INC280 versus time profiles


Enrollment: 39
Actual Study Start Date: March 25, 2013
Estimated Study Completion Date: January 31, 2018
Estimated Primary Completion Date: January 1, 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: INC280
The protocol consists of two independent parts (Dose-Determining Part and Dose Expansion Part). Approximately 6 patients will be treated with INC280 300 mg twice a day in the Dose-Determining Part. Approximately 50 patients will be treated with INC280 in the Dose Expansion Part. The dose for the Expansion Part can be lower, equal or higher than in the Dose-Determining Part will be determined after the Dose Determining Part at the dose decision analysis.
Drug: INC280
INC280 will be administered orally and continuously on a twice a day dosing schedule.

Detailed Description:

This study is designed as a Phase II, single arm, open-label, multicenter study to evaluate the safety and efficacy of INC280 as first-line treatment in patients with advanced hepatocellular carcinoma (HCC) who are not eligible for or had disease progression after surgical or locoregional therapies, with c- MET dysregulation.

The study includes a Dose-Determining Part and a Dose Expansion Part. Pharmacokinetic and safety profiles of INC280 in the setting of liver dysfunction will be determined in the Dose-Determining Part. The Dose Expansion Part will start when the appropriate dose for patients with liver dysfunction is determined based on pharmacokinetics (PK) and safety data from the Dose-Determining Part and other INC280 ongoing clinical studies.

  Eligibility

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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.
  • Other protocol-defined inclusion criteria may apply.

Exclusion Criteria:

  • 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.
  • Other protocol-defined exclusion criteria may apply.
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01737827


Locations
China, Guangdong
Novartis Investigative Site
Guangzhou, Guangdong, China, 510515
China, Jiangsu
Novartis Investigative Site
Nanjing, Jiangsu, China, 210002
China, Shanxi
Novartis Investigative Site
Xi'an, Shanxi, China, 710032
China, Zhejiang
Novartis Investigative Site
Hangzhou, Zhejiang, China, 310016
China
Novartis Investigative Site
Beijing, China, 100039
Novartis Investigative Site
Guangzhou, China, 510060
Novartis Investigative Site
Shanghai, China, 200032
Hong Kong
Novartis Investigative Site
Hong Kong, Hong Kong
Singapore
Novartis Investigative Site
Singapore, Singapore, 169610
Taiwan
Novartis Investigative Site
Tainan, Taiwan ROC, Taiwan, 70421
Novartis Investigative Site
Taipei, Taiwan, 10002
Thailand
Novartis Investigative Site
Khon Kaen, THA, Thailand, 40002
Novartis Investigative Site
Bangkok, Thailand, 10330
Novartis Investigative Site
Bangkok, Thailand, 10700
Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
  More Information

Responsible Party: Novartis Pharmaceuticals
ClinicalTrials.gov Identifier: NCT01737827     History of Changes
Other Study ID Numbers: CINC280X2201
First Submitted: November 12, 2012
First Posted: November 30, 2012
Last Update Posted: August 10, 2017
Last Verified: August 2017

Keywords provided by Novartis ( Novartis Pharmaceuticals ):
INC280, advanced hepatocellular carcinoma, c-MET pathway dysregulation

Additional relevant MeSH terms:
Carcinoma
Carcinoma, Hepatocellular
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Adenocarcinoma
Liver Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Liver Diseases