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

Metastatic Colorectal Cancer Clinical Trial

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.

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT02205398
• Other study ID #: CINC280X2104
• Secondary ID: 2014-000579-20
• Status: Terminated
• Phase: Phase 1
• Start date: July 28, 2014
• Est. completion date: January 20, 2017

Study information

• Verified date: January 2019
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 13
• Est. completion date: January 20, 2017
• Est. primary completion date: January 20, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

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

Intervention

Drug:
• INC280

• cetuximab

Locations

Country	Name	City	State
Belgium	Novartis Investigative Site	Leuven
Canada	Novartis Investigative Site	Toronto	Ontario
France	Novartis Investigative Site	Lyon Cedex
France	Novartis Investigative Site	Toulouse Cedex 9
Germany	Novartis Investigative Site	Essen
Germany	Novartis Investigative Site	Wuerzburg
Italy	Novartis Investigative Site	Ancona	AN
Italy	Novartis Investigative Site	Milano	MI
Spain	Novartis Investigative Site	Barcelona	Catalunya
Spain	Novartis Investigative Site	Barcelona	Catalunya
Spain	Novartis Investigative Site	Hospitalet de LLobregat	Catalunya
Spain	Novartis Investigative Site	Valencia	Comunidad Valenciana
United States	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

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Countries where clinical trial is conducted

United States,  Belgium,  Canada,  France,  Germany,  Italy,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	during Cycle 1 and up to 4 weeks from the time of study treatment start
Secondary	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	During Cycle 1 Day 1 (C1D1) until treatment discontinuation for up to 2 years
Secondary	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.	Every 8 weeks from cycle 1, day 1 until the end of study for up to 3 years
Secondary	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.	Every 12 weeks until the end of study for up to 3 years
Secondary	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.	during the first 4 Cycles of treatment or up to 16 weeks from the time of study treatment start
Secondary	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	From Cycle 1 Day 1 until treatment discontinuation for up to 2 years
Secondary	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	From Cycle 1 Day 1 until treatment discontinuation for up to 2 years
Secondary	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.	Every 8 weeks from C1D1 until the end of study for up to 3 years