A clinical study with INC280 in combination with gefitinib in patients with non-small cell lung cancer
- Conditions
- on-Small Cell Lung CancerMedDRA version: 21.1Level: PTClassification code 10061873Term: Non-small cell lung cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2011-002569-39-DE
- Lead Sponsor
- ovartis Pharma Services AG
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 148
- Confirmed c-MET pathway dysregulation
- EGFR mutated NSCLC patient who have developed acquired resistance to EGFR inhibitor treatment
- Measurable disease as determined by RECIST version 1.1
-ECOG performance status =2
- Documented c-Met amplification
- Prior clinical benefit on EGFR inhibitors and then subsequent progression
- = 18 years of age
- Life expectancy =3 months
Other protocol inclusion criteria may apply
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range
- Previous treatment with a c-MET inhibitor or HGF-targeting therapy
- Patients with documented EGFR T790M mutation
- Previous radiation therapy completed less than 4 weeks prior to dosing and, if present, any acute toxicity > grade 1
- history of cystic fibrosis
- history of acute or chronic pancreatitis, surgery of the pancreas, or any risk factors that may increase the risk of pancreatitis.
- presence or history of a malignant disease other than NSCLC that has been diagnosed and/or required therapy with the past 3 years
- Presence or history of interstitial lung disease or interstitial pneumonitis, including clinically significant radiation pneumonitis (i.e., affecting activities of daily living or requiring therapeutic intervention)
- Unable to swallow tablets once or twice daily
- Any unresolved toxicity from previous anticancer therapy greater than Grade 1 except alopecia.
- Unable to undergo an MRI or CT procedures
- Known history of HIV
- Undergone a bone marrow or solid organ transplant
- Pregnant or nursing
Other protocol exclusion criteria may apply
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: 1) Phase Ib: To estimate the MTD or RP2D of INC280 in combination with gefitinib in NSCLC patients who have c-MET gene dysregulation<br>2) Phase II: To estimate overall clinical activity of INC280 in combination with gefitinib in NSCLC patients with c-MET gene dysregulation;Secondary Objective: 1) To determine safety and tolerability of INC280 in combination with gefitinib<br>2) To estimate time dependent clinical activity of INC280 in combination with gefitinib<br>3) To characterize the PK profile of INC280 and gefitinib in NSCLC patient population and to assess potential drug interaction between INC280 and gefitinib;Primary end point(s): 1) Phase Ib : Frequency and characteristics of dose limitting toxicities (DLTs)<br>2) Phase II : Overall Response Rate of tumors per RECIST 1.1;Timepoint(s) of evaluation of this end point: 1) From date of treatment until DLT, up to 52 weeks<br>2) From date of treatment until disease progression, up to 100 weeks
- Secondary Outcome Measures
Name Time Method Secondary end point(s): 1) Overall Survival (OS)<br>2) Frequency, duration and severity of adverse events (AEs)<br>3) Plasma concentration of INC280<br>4) Progression Free Survival (PFS)<br>5) Plasma concentration of gefitinib<br>6) PK parameter AUC<br>7) PK parameter Cmax<br>8) PK parameter Tmax<br>9) PK parameter accumulation ratio<br>10) PK parameter half-life<br>11) number of SAEs, and severity of SAEs<br>12) number of AEs;Timepoint(s) of evaluation of this end point: 1) From date of treatment until death, up to 5 years<br>2) 30 days post study treatment<br>3) Day 1 of cycle 4<br>4) From date of treatment to the date of disease progression, up to 5 years<br>5, 6, 7, 8, 9, 10) Day 1 and 15 cycle 2, Day 1 of cycle 3 and 4<br>11 and 12) 30 days post study treatment