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| ID | Type | Description | Link |
|---|---|---|---|
| 2014-000579-20 | EudraCT Number |
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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| c-MET positive mCRC and HNSCC | Experimental | c-MET positive and K/NRAS WT mCRC and c-MET positive HNSCC patients |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| INC280 | Drug |
| ||
| cetuximab |
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Novartis Pharmaceuticals | Novartis Pharmaceuticals | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Massachusetts General Hospital Head & Neck | Boston | Massachusetts | 02114 | United States | ||
| Memorial Sloan Kettering MSKCC NY |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 32410080 | Derived | 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. |
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|
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| New York |
| New York |
| 10017 |
| United States |
| University of Utah / Huntsman Cancer Institute Onc Dept | Salt Lake City | Utah | 84103 | United States |
| Novartis Investigative Site | Leuven | 3000 | Belgium |
| Novartis Investigative Site | Toronto | Ontario | M5G 1X6 | Canada |
| Novartis Investigative Site | Lyon | 69373 | France |
| Novartis Investigative Site | Toulouse | 31059 | France |
| Novartis Investigative Site | Essen | 45147 | Germany |
| Novartis Investigative Site | Würzburg | 97080 | Germany |
| Novartis Investigative Site | Ancona | AN | 60126 | Italy |
| Novartis Investigative Site | Milan | MI | 20162 | Italy |
| Novartis Investigative Site | Barcelona | Catalonia | 08003 | Spain |
| Novartis Investigative Site | Barcelona | Catalonia | 08035 | Spain |
| Novartis Investigative Site | L'Hospitalet de Llobregat | Catalonia | 08907 | Spain |
| Novartis Investigative Site | Valencia | Valencia | 46010 | Spain |
| ID | Term |
|---|---|
| D000077195 | Squamous Cell Carcinoma of Head and Neck |
| D015179 | Colorectal Neoplasms |
| D002294 | Carcinoma, Squamous Cell |
| D009369 | Neoplasms |
| D007818 | Laryngeal Diseases |
| D012004 | Rectal Neoplasms |
| ID | Term |
|---|---|
| D002277 | Carcinoma |
| D009375 | Neoplasms, Glandular and Epithelial |
| D009370 | Neoplasms by Histologic Type |
| D006258 | Head and Neck Neoplasms |
| D009371 | Neoplasms by Site |
| D007414 | Intestinal Neoplasms |
| D005770 | Gastrointestinal Neoplasms |
| D004067 | Digestive System Neoplasms |
| D004066 | Digestive System Diseases |
| D005767 | Gastrointestinal Diseases |
| D003108 | Colonic Diseases |
| D007410 | Intestinal Diseases |
| D012002 | Rectal Diseases |
| D018307 | Neoplasms, Squamous Cell |
| D012140 | Respiratory Tract Diseases |
| D010038 | Otorhinolaryngologic Diseases |
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| ID | Term |
|---|---|
| C000613976 | capmatinib |
| D000068818 | Cetuximab |
| ID | Term |
|---|---|
| D061067 | Antibodies, Monoclonal, Humanized |
| D000911 | Antibodies, Monoclonal |
| D000906 | Antibodies |
| D007136 | Immunoglobulins |
| D007162 | Immunoproteins |
| D001798 | Blood Proteins |
| D011506 | Proteins |
| D000602 | Amino Acids, Peptides, and Proteins |
| D012712 | Serum Globulins |
| D005916 | Globulins |
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