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A Safety and Efficacy Study of INC280 and Gefitinib in Patients With EGFR Mutated, c-MET-amplified NSCLC Who Have Progressed After EGFRi Treatment

NCT01610336

Description:

This study will assess the safety and efficacy of escalating doses INC280 when added to gefitinib in patients with lung cancer that are known to have dysregulation of the c-MET pathway and who have failed after benefiting on a prior treatment with either gefitinib or erlotinib.

Related Conditions:
  • Non-Small Cell Lung Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: A Safety and Efficacy Study of INC280 and Gefitinib in Patients With EGFR Mutated, c-MET-amplified NSCLC Who Have Progressed After EGFRi Treatment
  • Official Title: A Phase IB/II, Open Label, Multicenter Study of INC280 Administered Orally in Combination With Gefitinib in Adult Patients With EGFR Mutated, c-MET-amplified Non-small Cell Lung Cancer Who Have Progressed After EGFR Inhibitor Treatment

Clinical Trial IDs

  • ORG STUDY ID: CINC280X2202
  • SECONDARY ID: 2011-002569-39
  • NCT ID: NCT01610336

Conditions

  • Non-small Cell Lung Cancer

Interventions

DrugSynonymsArms
INC280INC280+gefitinib

Purpose

This study will assess the safety and efficacy of escalating doses INC280 when added to gefitinib in patients with lung cancer that are known to have dysregulation of the c-MET pathway and who have failed after benefiting on a prior treatment with either gefitinib or erlotinib.

Detailed Description

      Patients will be treated INC280 and gefitinib(250mg) daily. Dose escalation for INC280 will
      be performed. Each cohort for the phase IB part will consist of 3 to 6 newly enrolled
      patients. A twice daily administration of INC280 may be investigated if deemed appropriate
      based on emerging results from ongoing clinical trials.
    

Trial Arms

NameTypeDescriptionInterventions
INC280+gefitinibExperimentalINC280+gefitinib
  • INC280

Eligibility Criteria

        Inclusion Criteria:

          -  Documented EGFR mutation

          -  Documented c-MET dysregulation

          -  Prior clinical benefit on EGFR inhibitors and then subsequent progression

             -≥ 18 year old

          -  Life expectancy of ≥ 3 months

          -  ECOG performance status ≤ 2

        Exclusion Criteria:

          -  Unable to swallow tables once or twice daily

          -  Previous treatment with c-MET inhibitor

          -  Any unresolved toxicity form previous anticancer therapy greater than grade 1

          -  History of cystic fibrosis

          -  History of acute or chronic pancreatitis

          -  Unable to undergo MRI or CT sans

          -  Known history of HIV

          -  Undergone a bone marrow or solid organ transplant

          -  Clinically significant wound or lung tumor lesions with increased likelihood of
             bleeding

          -  Pregnant or nursing

        Other protocol-defined inclusion/exclusion criteria may apply
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Phase Ib: Frequency and characteristics of dose limiting toxicities (DLTs) to the
Time Frame:From date of treatment until DLT, up to 52weeks
Safety Issue:
Description:1 cycle= 28 days

Secondary Outcome Measures

Measure:Overall survival (OS)
Time Frame:From date of treatment until death, up to 5 years
Safety Issue:
Description:OS is defined as the time from the date of treatment to the date of death from any cause.
Measure:Frequency, duration, and severity of adverse events (AEs)
Time Frame:30 days post study treatment
Safety Issue:
Description:Safety via monitoring of AEs
Measure:Inhibition of c-MET signaling by pre- and post- treatment immunohistochemistry of p-c-MET,
Time Frame:Day 15 of cycle 1
Safety Issue:
Description:1 cycle= 28 days
Measure:Plasma concentration of INC280
Time Frame:Day 1 of cycle 4
Safety Issue:
Description:1 cycle= 28 days
Measure:Progression free survival (PFS)
Time Frame:From date of treatment to the date of disease progression, up to 5 years
Safety Issue:
Description:PFS is defined as the time from the date of treatment to the date of event defined as the first documented progression per RECIST or death due to any cause.
Measure:Plasma concentration of gefitinib
Time Frame:Day 1 and 15 cycle 2, Day 1 of cycle 3 and 4
Safety Issue:
Description:1 cycle= 28 days
Measure:PK parameters AUC
Time Frame:Day 1 and 15 cycle 2, Day 1 of cycle 3 and 4
Safety Issue:
Description:1 cycle= 28 days
Measure:PK parameters Cmax
Time Frame:Day 1 and 15 cycle 2, Day 1 of cycle 3 and 4
Safety Issue:
Description:1 cycle= 28 days
Measure:PK parameters Tmax
Time Frame:Day 1 and 15 cycle 2, Day 1 of cycle 3 and 4
Safety Issue:
Description:1 cycle= 28 days
Measure:PK parameters accumulation ration
Time Frame:Day 1 and 15 cycle 2, Day 1 of cycle 3 and 4
Safety Issue:
Description:1 cycle= 28 days
Measure:PK parameters half- life
Time Frame:Day 1 and 15 cycle 2, Day 1 of cycle 3 and 4
Safety Issue:
Description:1 cycle= 28 days
Measure:number of SAE, and severity of serious adverse events (SAEs)
Time Frame:30 days post study treatment
Safety Issue:
Description:Safety via monitoring SAEs
Measure:number of AE
Time Frame:30 days post study treatment
Safety Issue:
Description:via monitoring changes in physical examination, clinical laboratory parameters, vital signs and ECGs

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Novartis Pharmaceuticals

Trial Keywords

  • EGFR
  • c-MET
  • Lung cancer
  • Gefitinib
  • Erlotinib

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