Study of Safety and Efficacy of INC280 and Cetuximab, in Adult c-MET Positive mCRC and HNSCC Patients After Progression on Cetuximab or Panitumumab Therapy

Phase 1TerminatedNCT02205398

Novartis Pharmaceuticals13 enrolled

Overview

This was 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 was to be explored in c-MET positive mCRC and HNSCC patients whose disease progressed on cetuximab or panitumumab treatment. The dose escalation part was to be guided by a Bayesian Logistic Regression Model with overdose control. At MTD/RDE, additional mCRC and HNSCC patients who progressed on cetuximab or panitumumab treatment were to 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 were to receive INC280 on a continuous bid dosing regimen and cetuximab every week. A treatment cycle was defined as 28 days with no scheduled break between cycles. The trial was terminated because of difficulties in identifying patients who met the eligibility criteria.

Study Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Squamous Cell Carcinoma of Head and Neck (SCCHN)Metastatic Colorectal Cancer

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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

Locations (15)

Massachusetts General Hospital Head & Neck

Boston, Massachusetts, United States

Memorial Sloan Kettering MSKCC NY

New York, New York, United States

University of Utah / Huntsman Cancer Institute Onc Dept

Salt Lake City, Utah, United States

Novartis Investigative Site

Leuven, Belgium

Novartis Investigative Site

Toronto, Ontario, Canada

Novartis Investigative Site

Lyon, France

Novartis Investigative Site

Toulouse, France

Novartis Investigative Site

Essen, Germany

Novartis Investigative Site

Würzburg, Germany

Novartis Investigative Site

Ancona, AN, Italy

...and 5 more locations

Outcomes

Primary Outcomes

Incidence of Dose Limiting Toxicities (DLTs)

To estimate the MTD and/or RDE of INC280 in combination with cetuximab in c-MET positive mCRC and HNSCC patients as measured by the incidence of DLTs in Cycle 1. A treatment cycle was defined as 28 days with no scheduled break between cycles.

Time frame: during Cycle 1 and up to 4 weeks from the time of study treatment start

Secondary Outcomes

Frequency of Adverse Events (AEs)/Serious Adverse Events (SAEs)

To characterize the safety and tolerability of the INC280 and cetuximab combination as measured by the frequency of AEs/SAEs in patients treated with the combination of INC280 and cetuximab

Time frame: During Cycle 1 Day 1 (C1D1) until treatment discontinuation for up to 2 years

Overall Response Rate

To assess preliminary anti-tumor activity of the INC280 and cetuximab combination as measured by Overall Response Rate in patients treated with the combination of INC280 and cetuximab. The end of study was upon completion of the survival follow-up period of the last patient treated with the combination of INC280 and cetuximab. A treatment cycle was defined as 28 days with no scheduled break between cycles.

Time frame: Every 8 weeks from cycle 1, day 1 until the end of study for up to 3 years

Overall Survival

To assess additional clinical activity of the INC280 and cetuximab combination as measured by Overall Survival for patients in the expansion part of the study. The end of study was upon completion of the survival follow-up period of the last patient treated with the combination of INC280 and cetuximab.

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

To characterize the PK profile of INC280 with cetuximab combination as measured by time versus plasma concentration profiles and basic PK parameters of INC280. A treatment cycle was defined as 28 days with no scheduled break between cycles.

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)

To characterize the safety and tolerability of the INC280 and cetuximab combination as measured by severity of AEs/SAEs in patients treated with the combination of INC280 and cetuximab

Time frame: From Cycle 1 Day 1 until treatment discontinuation for up to 2 years

Frequency of dose treatment interruptions and reductions

To characterize the safety and tolerability of the INC280 and cetuximab combination as measured by the frequency of dose interruptions and dose reductions in patients treated with the combination of INC280 and cetuximab

Time frame: From Cycle 1 Day 1 until treatment discontinuation for up to 2 years

Progression Free Survival

To assess preliminary anti-tumor activity of the INC280 and cetuximab combination as measured by Progression Free Survival in patients treated with the combination of INC280 and cetuximab.The end of study was upon completion of the survival follow-up period of the last patient treated with the combination of INC280 and cetuximab.

Time frame: Every 8 weeks from C1D1 until the end of study for up to 3 years

Study of Safety and Efficacy of INC280 and Cetuximab, in Adult c-MET Positive mCRC and HNSCC Patients After Progression on Cetuximab or Panitumumab Therapy

Overview

Conditions

Interventions

Eligibility

Locations (15)

Outcomes

Primary Outcomes

Secondary Outcomes