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

January 17, 2019 updated by: Novartis Pharmaceuticals

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.

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 Overview

Status

Terminated

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

13

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Belgium
      • Leuven, Belgium, 3000
        • Novartis Investigative Site
  • Canada
    • Ontario
      • Toronto, Ontario, Canada, M5G 1X6
        • Novartis Investigative Site
  • France
      • Lyon Cedex, France, 69373
        • Novartis Investigative Site
      • Toulouse Cedex 9, France, 31059
        • Novartis Investigative Site
  • Germany
      • Essen, Germany, 45147
        • Novartis Investigative Site
      • Wuerzburg, Germany, 97080
        • Novartis Investigative Site
  • Italy
    • AN
      • Ancona, AN, Italy, 60126
        • Novartis Investigative Site
    • MI
      • Milano, MI, Italy, 20162
        • Novartis Investigative Site
  • Spain
    • Catalunya
      • Barcelona, Catalunya, Spain, 08035
        • Novartis Investigative Site
      • Barcelona, Catalunya, Spain, 08003
        • Novartis Investigative Site
      • Hospitalet de LLobregat, Catalunya, Spain, 08907
        • Novartis Investigative Site
    • Comunidad Valenciana
      • Valencia, Comunidad Valenciana, Spain, 46010
        • Novartis Investigative Site
  • United States
    • Massachusetts
      • Boston, Massachusetts, United States, 02114
        • Massachusetts General Hospital Head & Neck
    • New York
      • New York, New York, United States, 10017
        • Memorial Sloan Kettering MSKCC NY
    • Utah
      • Salt Lake City, Utah, United States, 84103
        • University of Utah / Huntsman Cancer Institute Onc Dept

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: c-MET positive mCRC and HNSCC
c-MET positive and K/NRAS WT mCRC and c-MET positive HNSCC patients
Drug: INC280
Drug: cetuximab

What is the study measuring?

Primary Outcome Measures

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

Outcome Measure
Measure Description
Time Frame
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
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
Overall Response Rate
Time Frame: Every 8 weeks from cycle 1, day 1 until the end of study for up to 3 years
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
Overall Survival
Time Frame: Every 12 weeks until the end of study for up to 3 years
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
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
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
Severity of Adverse Events (AEs)/Serious Adverse Events (SAEs)
Time Frame: From Cycle 1 Day 1 until treatment discontinuation for up to 2 years
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
Frequency of dose treatment interruptions and reductions
Time Frame: From Cycle 1 Day 1 until treatment discontinuation for up to 2 years
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
Progression Free Survival
Time Frame: Every 8 weeks from C1D1 until the end of study for up to 3 years
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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Novartis Pharmaceuticals

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

July 28, 2014

Primary Completion (Actual)

January 20, 2017

Study Completion (Actual)

January 20, 2017

Study Registration Dates

First Submitted

July 25, 2014

First Submitted That Met QC Criteria

July 29, 2014

First Posted (Estimate)

July 31, 2014

Study Record Updates

Last Update Posted (Actual)

January 22, 2019

Last Update Submitted That Met QC Criteria

January 17, 2019

Last Verified

January 1, 2019

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CINC280X2104
  • 2014-000579-20 (EudraCT Number)

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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