Metastatic Colorectal Cancer, Squamous Cell Carcinoma of Head and Neck (SCCHN)
Conditions
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
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.
Interventions
DRUGINC280
DRUGcetuximab
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of Dose Limiting Toxicities (DLTs) | 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
| Measure | Time frame | Description |
|---|---|---|
| Overall Response Rate | 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. |
| Overall Survival | 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. |
| Time versus plasma concentration profiles and basic PK parameters of INC280 | 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. |
| Frequency of Adverse Events (AEs)/Serious Adverse Events (SAEs) | 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 |
| Frequency of dose treatment interruptions and reductions | 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 |
| Progression Free Survival | 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. |
| Severity of Adverse Events (AEs)/Serious Adverse Events (SAEs) | 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 |
Countries
Belgium, Canada, France, Germany, Italy, Spain, United States
Outcome results
None listed