Overview

This trial is active, not recruiting.

Conditions squamous cell carcinoma of head and neck,, metastatic colorectal cancer
Treatments inc280, cetuximab
Phase phase 1/phase 2
Targets c-MET, EGFR, KRAS
Sponsor Novartis Pharmaceuticals
Start date July 2014
End date January 2018
Trial size 13 participants
Trial identifier NCT02205398, 2014-000579-20, CINC280X2104

Summary

This is an open-label, phase Ib, multicenter clinical trial to determine the MTD/RDE of the orally administered c-MET inhibitor INC280 in combination with cetuximab. This combination will be explored in c-MET positive mCRC and HNSCC patients whose disease progressed on cetuximab or panitumumab treatment. The dose escalation part will be guided by a Bayesian Logistic Regression Model with overdose control. At MTD/RDE, additional mCRC and HNSCC patients who have progressed on cetuximab or panitumumab treatment will be enrolled in two expansion groups to further assess the anti-tumor activity and the safety and tolerability of the combination of INC280 and cetuximab. Patients will receive INC280 on a continuous bid dosing regimen and cetuximab every week. A treatment cycle is defined as 28 days with no scheduled break between cycles.

United States Massachusetts, New York, and Utah
Other Countries No locations recruiting

Study Design

Intervention model single group assignment
Masking open label
Primary purpose treatment
Arm
(Experimental)
c-MET positive and K/NRAS WT mCRC and c-MET positive HNSCC patients
inc280
cetuximab

Primary Outcomes

Measure
Incidence of Dose Limiting Toxicities (DLTs)
time frame: during Cycle 1 and up to 4 weeks from the time of study treatment start

Secondary Outcomes

Measure
Frequency of Adverse Events (AEs)/Serious Adverse Events (SAEs)
time frame: During Cycle 1 Day 1 (C1D1) until treatment discontinuation for up to 2 years
Overall Response Rate
time frame: Every 8 weeks from cycle 1, day 1 until the end of study for up to 3 years
Overall Survival
time frame: Every 12 weeks until the end of study for up to 3 years
Time versus plasma concentration profiles and basic PK parameters of INC280
time frame: during the first 4 Cycles of treatment or up to 16 weeks from the time of study treatment start
Severity of Adverse Events (AEs)/Serious Adverse Events (SAEs)
time frame: From Cycle 1 Day 1 until treatment discontinuation for up to 2 years
Frequency of dose treatment interruptions and reductions
time frame: From Cycle 1 Day 1 until treatment discontinuation for up to 2 years
Progression Free Survival
time frame: Every 8 weeks from C1D1 until the end of study for up to 3 years

Eligibility Criteria

Male or female participants at least 18 years old.

Inclusion Criteria: - Male or female aged ≥ 18 years - Metastatic colorectal cancer or head and neck squamous cell carcinoma - c-MET positive (defined by c-MET IHC intensity score +2 in ≥ 50% of tumor cells and MET gene copy number ≥ 5 by FISH or IHC intensity score +3 in ≥ 50% of tumor cells) and K/NRAS WT status for mCRC patients only - At least one previous line of treatment for the metastatic disease and the last treatment must have included cetuximab or panitumumab. Documentation of clinical benefit and subsequent progression on cetuximab or panitumumab as the most recent line of treatment is required for patients in the expansion part - Measurable disease as per RECIST v1.1 - ECOG performance status ≤ 2 Exclusion Criteria: - Prior treatment with c-MET/HGF inhibitors - History of severe reactions to cetuximab and/or panitumumab (except for G3 rash and G3 hypomagnesaemia) - History of acute or chronic pancreatitis - Active bleeding within 4 weeks prior to screening visit - Symptomatic brain metastases - Feeding tube dependence - Not adequate hematologic, renal and hepatic function Other protocol-defined inclusion/exclusion criteria may apply NVS Definition: List only the main study specific inclusion/exclusion criteria that patients will understand. Note: DO NOT cut/paste directly from the protocol. Do not include age and gender as part of this field. Age and gender are indicated in the 2 fields below. Always include statement "Other protocol-defined inclusion/exclusion criteria may apply" at the end of this section. Examples: Inclusion criteria: Patients within 7- 42 days of an acute myocardial infarction associated with left ventricular systolic dysfunction Qualifying Echocardiogram at Visit 1 Exclusion criteria: Presence of clinically overt heart failure Percutaneous coronary intervention (PCI) less than 24 hours before randomization previous treatment with aliskiren Other protocol-defined inclusion/exclusion criteria may apply.

Additional Information

Official title A Phase Ib, Open-label, Multicenter, Dose Escalation and Expansion Study, to Evaluate the Safety, Pharmacokinetics and Activity of INC280 in Combination With Cetuximab in c-MET Positive CRC and HNSCC Patients Who Have Progressed After Anti-EGFR Monoclonal Antibody Therapy.
Trial information was received from ClinicalTrials.gov and was last updated in September 2016.
Information provided to ClinicalTrials.gov by Novartis.