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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

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ClinicalTrials.gov Identifier: NCT02205398
Recruitment Status : Terminated
First Posted : July 31, 2014
Last Update Posted : January 22, 2019
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

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.


Condition or disease Intervention/treatment Phase
Squamous Cell Carcinoma of Head and Neck (SCCHN) Metastatic Colorectal Cancer Drug: INC280 Drug: cetuximab Phase 1

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 13 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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.
Actual Study Start Date : July 28, 2014
Actual Primary Completion Date : January 20, 2017
Actual Study Completion Date : January 20, 2017

Resource links provided by the National Library of Medicine


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



Primary Outcome Measures :
  1. 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.


Secondary Outcome Measures :
  1. 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

  2. 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.

  3. 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.

  4. 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.

  5. 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

  6. 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

  7. 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.



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02205398


Locations
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United States, Massachusetts
Massachusetts General Hospital Head & Neck
Boston, Massachusetts, United States, 02114
United States, New York
Memorial Sloan Kettering MSKCC NY
New York, New York, United States, 10017
United States, Utah
University of Utah / Huntsman Cancer Institute Onc Dept
Salt Lake City, Utah, United States, 84103
Belgium
Novartis Investigative Site
Leuven, Belgium, 3000
Canada, Ontario
Novartis Investigative Site
Toronto, Ontario, Canada, M5G 1X6
France
Novartis Investigative Site
Lyon Cedex, France, 69373
Novartis Investigative Site
Toulouse Cedex 9, France, 31059
Germany
Novartis Investigative Site
Essen, Germany, 45147
Novartis Investigative Site
Wuerzburg, Germany, 97080
Italy
Novartis Investigative Site
Ancona, AN, Italy, 60126
Novartis Investigative Site
Milano, MI, Italy, 20162
Spain
Novartis Investigative Site
Barcelona, Catalunya, Spain, 08003
Novartis Investigative Site
Barcelona, Catalunya, Spain, 08035
Novartis Investigative Site
Hospitalet de LLobregat, Catalunya, Spain, 08907
Novartis Investigative Site
Valencia, Comunidad Valenciana, Spain, 46010
Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
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Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Novartis Pharmaceuticals
ClinicalTrials.gov Identifier: NCT02205398    
Other Study ID Numbers: CINC280X2104
2014-000579-20 ( EudraCT Number )
First Posted: July 31, 2014    Key Record Dates
Last Update Posted: January 22, 2019
Last Verified: January 2019

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Novartis ( Novartis Pharmaceuticals ):
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
Additional relevant MeSH terms:
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Colorectal Neoplasms
Carcinoma, Squamous Cell
Squamous Cell Carcinoma of Head and Neck
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases
Neoplasms, Squamous Cell
Head and Neck Neoplasms
Cetuximab
Antineoplastic Agents, Immunological
Antineoplastic Agents