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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

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. Identifier: NCT01610336
Recruitment Status : Active, not recruiting
First Posted : June 4, 2012
Last Update Posted : July 2, 2019
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Non-small Cell Lung Cancer Drug: INC280 Phase 2

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 161 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: 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
Actual Study Start Date : April 5, 2012
Estimated Primary Completion Date : August 1, 2019
Estimated Study Completion Date : August 1, 2019

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Lung Cancer
Drug Information available for: Gefitinib

Arm Intervention/treatment
Experimental: INC280+gefitinib
Drug: INC280

Primary Outcome Measures :
  1. Phase Ib: Frequency and characteristics of dose limiting toxicities (DLTs) to the [ Time Frame: From date of treatment until DLT, up to 52weeks ]
    1 cycle= 28 days

  2. Phase II : Overall Response Rate of tumors per RECIST 1.1 [ Time Frame: from date of treatment until disease progression, up to 100 weeks ]

Secondary Outcome Measures :
  1. Overall survival (OS) [ Time Frame: From date of treatment until death, up to 5 years ]
    OS is defined as the time from the date of treatment to the date of death from any cause.

  2. Frequency, duration, and severity of adverse events (AEs) [ Time Frame: 30 days post study treatment ]
    Safety via monitoring of AEs

  3. Inhibition of c-MET signaling by pre- and post- treatment immunohistochemistry of p-c-MET, [ Time Frame: Day 15 of cycle 1 ]
    1 cycle= 28 days

  4. Plasma concentration of INC280 [ Time Frame: Day 1 of cycle 4 ]
    1 cycle= 28 days

  5. Progression free survival (PFS) [ Time Frame: From date of treatment to the date of disease progression, up to 5 years ]
    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.

  6. Plasma concentration of gefitinib [ Time Frame: Day 1 and 15 cycle 2, Day 1 of cycle 3 and 4 ]
    1 cycle= 28 days

  7. PK parameters AUC [ Time Frame: Day 1 and 15 cycle 2, Day 1 of cycle 3 and 4 ]
    1 cycle= 28 days

  8. PK parameters Cmax [ Time Frame: Day 1 and 15 cycle 2, Day 1 of cycle 3 and 4 ]
    1 cycle= 28 days

  9. PK parameters Tmax [ Time Frame: Day 1 and 15 cycle 2, Day 1 of cycle 3 and 4 ]
    1 cycle= 28 days

  10. PK parameters accumulation ration [ Time Frame: Day 1 and 15 cycle 2, Day 1 of cycle 3 and 4 ]
    1 cycle= 28 days

  11. PK parameters half- life [ Time Frame: Day 1 and 15 cycle 2, Day 1 of cycle 3 and 4 ]
    1 cycle= 28 days

  12. number of SAE, and severity of serious adverse events (SAEs) [ Time Frame: 30 days post study treatment ]
    Safety via monitoring SAEs

  13. number of AE [ Time Frame: 30 days post study treatment ]
    via monitoring changes in physical examination, clinical laboratory parameters, vital signs and ECGs

Information from the National Library of Medicine

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

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

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 identifier (NCT number): NCT01610336

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Sponsors and Collaborators
Novartis Pharmaceuticals
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Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals

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Responsible Party: Novartis Pharmaceuticals Identifier: NCT01610336     History of Changes
Other Study ID Numbers: CINC280X2202
2011-002569-39 ( EudraCT Number )
First Posted: June 4, 2012    Key Record Dates
Last Update Posted: July 2, 2019
Last Verified: June 2019
Individual Participant Data (IPD) Sharing Statement:
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

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: Yes

Keywords provided by Novartis ( Novartis Pharmaceuticals ):
Lung cancer

Additional relevant MeSH terms:
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Lung Neoplasms
Carcinoma, Non-Small-Cell Lung
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Lung Diseases
Respiratory Tract Diseases
Carcinoma, Bronchogenic
Bronchial Neoplasms
Antineoplastic Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action