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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

Primary Purpose

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

Status
Terminated
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
INC280
cetuximab
Sponsored by
Novartis Pharmaceuticals
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Squamous Cell Carcinoma of Head and Neck (SCCHN) focused on measuring INC280, c-MET inhibitor, cetuximab, metastatic colorectal cancer, head and neck, squamous cell carcinoma, resistance to cetuximab/panitumumab, SCCHN,, cancer, oral and nasal cavity, paranasal sinuses, pharynx, larynx, parotid glands, lympth nodes of neck, mucosal lining, epithelium, colon, large intestine, rectal cancer

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Massachusetts General Hospital Head & Neck
  • Memorial Sloan Kettering MSKCC NY
  • University of Utah / Huntsman Cancer Institute Onc Dept
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

c-MET positive mCRC and HNSCC

Arm Description

c-MET positive and K/NRAS WT mCRC and c-MET positive HNSCC patients

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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
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.
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 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.
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
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
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.

Full Information

First Posted
July 25, 2014
Last Updated
January 17, 2019
Sponsor
Novartis Pharmaceuticals
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1. Study Identification

Unique Protocol Identification Number
NCT02205398
Brief Title
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
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.
Study Type
Interventional

2. Study Status

Record Verification Date
January 2019
Overall Recruitment Status
Terminated
Study Start Date
July 28, 2014 (Actual)
Primary Completion Date
January 20, 2017 (Actual)
Study Completion Date
January 20, 2017 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Novartis Pharmaceuticals

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No

5. Study Description

Brief 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Squamous Cell Carcinoma of Head and Neck (SCCHN), Metastatic Colorectal Cancer
Keywords
INC280, c-MET inhibitor, cetuximab, metastatic colorectal cancer, head and neck, squamous cell carcinoma, resistance to cetuximab/panitumumab, SCCHN,, cancer, oral and nasal cavity, paranasal sinuses, pharynx, larynx, parotid glands, lympth nodes of neck, mucosal lining, epithelium, colon, large intestine, rectal cancer

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
13 (Actual)

8. Arms, Groups, and Interventions

Arm Title
c-MET positive mCRC and HNSCC
Arm Type
Experimental
Arm Description
c-MET positive and K/NRAS WT mCRC and c-MET positive HNSCC patients
Intervention Type
Drug
Intervention Name(s)
INC280
Intervention Type
Drug
Intervention Name(s)
cetuximab
Primary Outcome Measure Information:
Title
Incidence of Dose Limiting Toxicities (DLTs)
Description
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 Outcome Measure Information:
Title
Frequency of Adverse Events (AEs)/Serious Adverse Events (SAEs)
Description
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
Title
Overall Response Rate
Description
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
Title
Overall Survival
Description
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
Title
Time versus plasma concentration profiles and basic PK parameters of INC280
Description
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
Title
Severity of Adverse Events (AEs)/Serious Adverse Events (SAEs)
Description
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
Title
Frequency of dose treatment interruptions and reductions
Description
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
Title
Progression Free Survival
Description
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

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Novartis Pharmaceuticals
Organizational Affiliation
Novartis Pharmaceuticals
Official's Role
Study Director
Facility Information:
Facility Name
Massachusetts General Hospital Head & Neck
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02114
Country
United States
Facility Name
Memorial Sloan Kettering MSKCC NY
City
New York
State/Province
New York
ZIP/Postal Code
10017
Country
United States
Facility Name
University of Utah / Huntsman Cancer Institute Onc Dept
City
Salt Lake City
State/Province
Utah
ZIP/Postal Code
84103
Country
United States
Facility Name
Novartis Investigative Site
City
Leuven
ZIP/Postal Code
3000
Country
Belgium
Facility Name
Novartis Investigative Site
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M5G 1X6
Country
Canada
Facility Name
Novartis Investigative Site
City
Lyon Cedex
ZIP/Postal Code
69373
Country
France
Facility Name
Novartis Investigative Site
City
Toulouse Cedex 9
ZIP/Postal Code
31059
Country
France
Facility Name
Novartis Investigative Site
City
Essen
ZIP/Postal Code
45147
Country
Germany
Facility Name
Novartis Investigative Site
City
Wuerzburg
ZIP/Postal Code
97080
Country
Germany
Facility Name
Novartis Investigative Site
City
Ancona
State/Province
AN
ZIP/Postal Code
60126
Country
Italy
Facility Name
Novartis Investigative Site
City
Milano
State/Province
MI
ZIP/Postal Code
20162
Country
Italy
Facility Name
Novartis Investigative Site
City
Barcelona
State/Province
Catalunya
ZIP/Postal Code
08003
Country
Spain
Facility Name
Novartis Investigative Site
City
Barcelona
State/Province
Catalunya
ZIP/Postal Code
08035
Country
Spain
Facility Name
Novartis Investigative Site
City
Hospitalet de LLobregat
State/Province
Catalunya
ZIP/Postal Code
08907
Country
Spain
Facility Name
Novartis Investigative Site
City
Valencia
State/Province
Comunidad Valenciana
ZIP/Postal Code
46010
Country
Spain

12. IPD Sharing Statement

Citations:
PubMed Identifier
32410080
Citation
Delord JP, Argiles G, Fayette J, Wirth L, Kasper S, Siena S, Mesia R, Berardi R, Cervantes A, Dekervel J, Zhao S, Sun Y, Hao HX, Tiedt R, Vicente S, Myers A, Siu LL. A phase 1b study of the MET inhibitor capmatinib combined with cetuximab in patients with MET-positive colorectal cancer who had progressed following anti-EGFR monoclonal antibody treatment. Invest New Drugs. 2020 Dec;38(6):1774-1783. doi: 10.1007/s10637-020-00928-z. Epub 2020 May 14.
Results Reference
derived

Learn more about this trial

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

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