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

This study is currently recruiting participants. (see Contacts and Locations)
Verified September 2014 by Novartis
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:
NCT01737827
First received: November 12, 2012
Last updated: September 11, 2014
Last verified: September 2014
  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: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: 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

Resource links provided by NLM:


Further study details as provided by Novartis:

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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: Yes ]
    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 ] [ Designated as safety issue: Yes ]
    Change from baseline values.

  • Tolerability of study drug [ Time Frame: From date start of treatment until end of treatment, average 6 months from baseline ] [ Designated as safety issue: Yes ]
    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 ] [ Designated as safety issue: No ]
    Plasma concentration of INC280 versus time profiles. AUC=Area Under the Curve

  • Alpha-fetoprotein [ Time Frame: baseline, every 6 weeks up to 6 months ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    Plasma concentration of INC280 versus time profiles


Estimated Enrollment: 56
Study Start Date: March 2013
Estimated Study Completion Date: November 2015
Estimated Primary Completion Date: November 2015 (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

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
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
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01737827

Contacts
Contact: Novartis Pharmaceuticals +41613241111
Contact: Novartis Pharmaceuticals

Locations
China, Jiangsu
Novartis Investigative Site Recruiting
Nanjing, Jiangsu, China, 210002
China, Shanxi
Novartis Investigative Site Not yet recruiting
Xi'an, Shanxi, China, 710032
China, Zhejiang
Novartis Investigative Site Recruiting
Hangzhou, Zhejiang, China, 310016
China
Novartis Investigative Site Not yet recruiting
Beijing, China, 100039
Novartis Investigative Site Not yet recruiting
Shanghai, China, 200032
Hong Kong
Novartis Investigative Site Recruiting
Hong Kong, Hong Kong
Singapore
Novartis Investigative Site Recruiting
Singapore, Singapore, 169610
Thailand
Novartis Investigative Site Recruiting
Bangkok, Thailand, 10700
Novartis Investigative Site Recruiting
Bangkok, Thailand, 10330
Novartis Investigative Site Recruiting
Khon Kaen, Thailand, 40002
Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
  More Information

No publications provided

Responsible Party: Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier: NCT01737827     History of Changes
Other Study ID Numbers: CINC280X2201
Study First Received: November 12, 2012
Last Updated: September 11, 2014
Health Authority: China: Food and Drug Administration
Hong Kong: Department of Health
Singapore: Health Sciences Authority

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

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

ClinicalTrials.gov processed this record on October 23, 2014