Try our beta test site
IMPORTANT: Listing of a study on this site does not reflect endorsement by the National Institutes of Health. Talk with a trusted healthcare professional before volunteering for a study. Read more...

Clinical Study of Oral cMET Inhibitor INC280 in Adult Patients With EGFR Wild-type Advanced Non-small Cell Lung Cancer

This study is currently recruiting participants. (see Contacts and Locations)
Verified April 2017 by Novartis
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:
NCT02414139
First received: March 31, 2015
Last updated: April 24, 2017
Last verified: April 2017
  Purpose
A phase II study to evaluate antitumor activity of oral cMET inhibitor INC280 in adult patients with EGFR wild-type, advanced non-small cell lung cancer (NSCLC) as measured by overall response rate (ORR). The study will also evaluate safety and pharmacokinetics of INC280.

Condition Intervention Phase
Carcinoma, Non-Small-Cell Lung
Drug: INC280 (capmatinib)
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: No masking
Primary Purpose: Treatment
Official Title: A Phase II, Multicenter Study of Oral cMET Inhibitor INC280 in Adult Patients With EGFR Wild-type (wt), Advanced Non-small Cell Lung Cancer (NSCLC)

Resource links provided by NLM:


Further study details as provided by Novartis:

Primary Outcome Measures:
  • Overall Response Rate (ORR) [ Time Frame: at least 18 weeks ]
    Proportion of patients with a best overall response defined as complete response (CR) or partial response (PR) by Blinded Independent Review Committee (BIRC) assessment per RECIST 1.1


Secondary Outcome Measures:
  • Duration of Response (DOR) - Key Secondary [ Time Frame: at least 18 weeks ]
    Calculated as the time from the date of the first documented CR or PR by Blinded Independent Review Committee (BIRC) per RECIST 1.1 to the first documented progression or death due to any cause for patients with PR or CR.

  • Overall Response Rate (ORR) [ Time Frame: at least 18 weeks ]
    ORR (complete response (CR)+ partial response (PR)) per RECIST 1.1 by investigator assessment

  • Duration of Response (DOR) [ Time Frame: at least 18 weeks ]
    DOR per RECIST 1.1 by investigator assessment

  • Time to Response (TTR) [ Time Frame: at least 18 weeks ]
    TTR per RECIST 1.1 both by BIRC and investigator assessment

  • Disease Control Rate (DCR) [ Time Frame: at least 18 weeks ]
    DCR per RECIST 1.1 both by BIRC and investigator assessment

  • Progression-free Survival (PFS) [ Time Frame: at least 18 weeks ]
    PFS per RECIST 1.1 both by BIRC and investigator assessment

  • Overall Survival (OS) [ Time Frame: at least 18 weeks ]
    OS, defined as time from first dose of INC280 to death due to any cause

  • Number of patients with incidence of adverse events and serious adverse events, change in vital signs, laboratory results (hematology, blood chemistry, and urinalysis) and ECG. [ Time Frame: at least 18 weeks ]
    Safety of INC280

  • Cmax, Cmin and plasma concentration-time profiles of INC280 [ Time Frame: 6 weeks ]
    Pharmacokinetics of INC280 and metabolite CMN288


Estimated Enrollment: 318
Actual Study Start Date: June 11, 2015
Estimated Study Completion Date: January 28, 2020
Estimated Primary Completion Date: January 28, 2020 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: cMET GCN ≥ 6
Pre-treated patients with cMET GCN ≥ 6 treated with INC280 at 400mg BID
Drug: INC280 (capmatinib)
Experimental: cMET GCN ≥ 4 and < 6
Pre-treated patients with cMET GCN ≥ 4 and < 6 treated with INC280 at 400 mgBID
Drug: INC280 (capmatinib)
Experimental: cMET GCN < 4
Pre-treated patients with cMET GCN < 4 treated with INC280 at 400mg BID
Drug: INC280 (capmatinib)
Experimental: cMET mutations
Pre-treated patients with cMET mutations regardless of cMET GCN treated with INC280 at 400mg BID
Drug: INC280 (capmatinib)
Experimental: cMET dysregulation - treatment-naïve
Treatment-naïve patients with cMET dysregulation treated with INC280 at 400mg
Drug: INC280 (capmatinib)

  Eligibility

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

Inclusion Criteria:

  • Stage IIIB or IV NSCLC (any histology) at the time of study entry
  • Histologically or cytologically confirmed diagnosis of NSCLC that is:

    1. EGFR wt as per patient standard of care by a validated test
    2. AND ALK-negative rearrangement as part of the patient standard of care by a validated test
    3. AND (by central assessment) either:

      • Cohort 1: Pre-treated patients with cMET GCN ≥ 6 or
      • Cohort 2: Pre-treated patients with cMET GCN ≥4 and < 6, or
      • Cohort 3: Pre-treated patients with cMET GCN < 4, or
      • Cohort 4: Pre-treated patients with cMET mutations regardless of cMET GCN, or
      • Cohort 5: Treatment-naïve patients with cMET dysregulation
  • To be eligible for Cohorts 1-4, patients must have failed one or two prior lines of systemic therapy for advanced/metastatic disease
  • To be eligible for Cohort 5, patients must not have received any systemic therapy for advanced/metastatic disease
  • At least one measurable lesion as defined by RECIST 1.1
  • Patients must have recovered from all toxicities related to prior anticancer therapies to grade ≤ 1 (CTCAE v 4.03). Patients with any grade of alopecia are allowed to enter the study.
  • Patients must have adequate organ function
  • ECOG performance status (PS) of 0 or 1 Details and other protocol-defined inclusion criteria may apply

Exclusion Criteria:

  • Prior treatment with crizotinib, or any other cMET or HGF inhibitor
  • Patients with characterized EGFR mutations that predict sensitivity to EGFR therapy, including, but not limited to exon 19 deletions and exon 21 mutations
  • Patients with characterized ALK-positive rearrangement
  • Clinically significant, uncontrolled heart diseases.
  • Patients receiving treatment with medications that cannot be discontinued at least 1 week prior to first INC280 treatment and for the duration of the study:

    • Strong and moderate inhibitors of CYP3A4
    • Strong inducers of CYP3A4
  • Impairment of GI function or GI disease that may significantly alter the absorption of INC280
  • Patients receiving treatment with any enzyme-inducing anticonvulsant
  • Applicable to Cohorts 1-4 only: Previous anti-cancer and investigational agents within 4 weeks or ≤ 5 x half-life of the agent (whichever is longer) before first dose
  • Pregnant or nursing women
  • Women of child-bearing potential, unless they are using highly effective methods of contraception
  • Sexually active males unless they use a condom during intercourse

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: NCT02414139

Contacts
Contact: Novartis Pharmaceuticals 1-888-669-6682 trialandresults.registries@novartis.com
Contact: Novartis Pharmaceuticals +41613241111 trialandresults.registries@novartis.com

  Show 138 Study Locations
Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
  More Information

Responsible Party: Novartis Pharmaceuticals
ClinicalTrials.gov Identifier: NCT02414139     History of Changes
Other Study ID Numbers: CINC280A2201
2014-003850-15 ( EudraCT Number )
Study First Received: March 31, 2015
Last Updated: April 24, 2017
Individual Participant Data  
Plan to Share IPD: Undecided
Plan Description:

Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.

This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com


Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Novartis:
Non Small Cell Lung
cMET

Additional relevant MeSH terms:
Carcinoma, Non-Small-Cell Lung
Carcinoma, Bronchogenic
Bronchial Neoplasms
Lung Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases

ClinicalTrials.gov processed this record on April 28, 2017