Primary: To evaluate the antitumor activity of INC280, as measured by overall response rate (ORR) as by a blinded independent review committee, by cohort.Secondary: Duration of response (DOR), ORR and DOR by investigator, time to response (TTR),…
ID
Source
Brief title
Condition
- Respiratory and mediastinal neoplasms malignant and unspecified
- Respiratory tract neoplasms
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
ORR by blinded independent review committee.
Secondary outcome
DOR, ORR and DOR by investigator, TTR, DCTR, PFS, OS, adverse events, PK
parameters.
Background summary
cMET dysregulation (amplification, overexpression, mutation) constitutes an
oncogenic driver in several tumor types, including lung cancer. Currently,
there is no approved therapy for tumors with cMET dysregulations and therefore
there is a high unmet medical need to develop therapy capable of cMET
inhibition for the treatment of these tumors.
INC280 is a highly potent and selective cMET inhibitor in biochemical and
cellular assays and capable of blocking cMET activation. Overall, the emerging
preclinical and clinical data suggest that INC280 may have a favorable
benefit-risk ratio for the treatment of cMET dysregulated advanced lung cancer.
The primary objective of this study is to evaluate the antitumor activity of
INC280 in patients with EGFR wild-type, advanced non-small cell lung cancer
(NSCLC). The primary measure overall response rate as determined by a blinded
independent review committee.
Study objective
Primary:
To evaluate the antitumor activity of INC280, as measured by overall response
rate (ORR) as by a blinded independent review committee, by cohort.
Secondary:
Duration of response (DOR), ORR and DOR by investigator, time to response
(TTR), disease control rate (DCTR), progression free survival (PFS), overall
survival (OS), safety and tolerability, PK profile.
Study design
Multicenter phase II open-label 5 cohort study of INC280 monotherapy (800 mg
twice daily, tablets).
Prescreening for cMET mutation and amplification. Cohorts based on cMET
mutation / amplification status.
Treatment period until disease progression or unacceptable side effects.
Approx. 456 patients (69 per cohort 1a, 1b, 2, 3, 4 and 27 per cohort 5a, 5b
and 7 and 30 in cohort 6).
Intervention
Treatment with INC280.
Study burden and risks
Risk: Adverse effects of INC280.
Burden: Cycles of 3 weeks. Cycle 1: 2 visits, cycle 2 onwards 1 visit. Duration
mostly 2-4 hours.
Physical examination: Once per cycle.
Blood tests (5-35 ml/occasion): Once per cycle.
ECG: 5 visits in total (up to 5 ECGs per visit).
CT-/MRI-scan: every 6 weeks.
Questionnaires (EQ-5D-4L, QLQ-C30, LC13): every 6 weeks
Optional tumor biopsies: maximum of 3 and optional 20 mL blood for biomarkers.
Optional storage and use of the remaining blood and tissue for future research.
Haaksbergweg 16
Amsterdam 1101 BX
NL
Haaksbergweg 16
Amsterdam 1101 BX
NL
Listed location countries
Age
Inclusion criteria
• Female and male patients >= 18 years of age.
• Stage IIIB or IV NSCLC.
• Histologically or cytologically confirmed diagnosis of NSCLC (see protocol
page 42 for details):
• EGFR wild-type.
• ALK-negative rearrangement.
• Pre-treated Patients with cMET GCN>=6 and <10 (cohort 1a), Patients with cMET
GCN>=10 (cohort 1b), GCN>=4 and <6 (cohort 2), GCN<4 (cohort 3), cMET mutations
(cohort 4). Treatment naive patients with cMET GCN >= 10 (cohort 5a), cMET
mutations (cohort 5b), Pre-treated patients (1 treatment line) with either cMET
GCN >= 10 without cMET mutations or cMET mutations regardless of cMET GCN
(cohort 6 = expansion group). Treatment naive patients with cMET mutations,
regardless of cMET GCN (Cohort 7 = expansion group)
• For cohort 1-4 patients must have received one or two prior lines of systemic
therapy for advanced/metastatic disease (stage IIIB or IV NSCLC). For cohort 5
patients must have received no prior lines of systemic therapy for
advanced/metastatic disease (stage IIIB or IV NSCLC). See protocol page 42 for
details.
• Measurable disease. See protocol page 42 for details.
• ECOG performance status 0-1.
Exclusion criteria
• Prior treatment with crizotinib, or any other cMET or HGF inhibitor.
• Characterized EGFR mutations that predict sensitivity to EGFR therapy.
• Characterized ALK-positive rearrangement.
• Symptomatic CNS metastases who are neurologically unstable or have required
increasing doses of steroids within the 2 weeks prior to study entry.
• Clinically significant, uncontrolled heart diseases. See protocol page 44 for
details.
• Thoracic radiotherapy to lung fields <= 4 weeks prior to starting INC280. For
all other anatomic sites, radiotherapy <= 2 weeks prior to starting INC280.
Palliative radiotherapy for bone lesions <= 2 weeks prior to starting INC280 is
allowed. See protocol page 44 for details.
• Major surgery within 4 weeks prior to starting INC280. See protocol page 44
for details.
• Strong and moderate inhibitors of CYP3A4, strong inducers of CYP3A4, proton
pump inhibitors.
• Unstable or increasing doses of corticosteroids, enzyme-inducing
anticonvulsant. See protocol page 45 for details)
• Pregnancy, lactation, insufficient contraception for females of childbearing
potential.
• Sexually active males unless they use a condom during intercourse.
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| Other | clinicaltrials.gov; registratienummer n.n.b. |
| EudraCT | EUCTR201400385015-NL |
| CCMO | NL52842.056.15 |