Description:
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.
Title
- 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.
Clinical Trial IDs
- ORG STUDY ID:
CINC280X2104
- SECONDARY ID:
2014-000579-20
- NCT ID:
NCT02205398
Conditions
- Squamous Cell Carcinoma of Head and Neck (SCCHN)
- Metastatic Colorectal Cancer
Interventions
Drug | Synonyms | Arms |
---|
INC280 | | c-MET positive mCRC and HNSCC |
cetuximab | | c-MET positive mCRC and HNSCC |
Purpose
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.
Trial Arms
Name | Type | Description | Interventions |
---|
c-MET positive mCRC and HNSCC | Experimental | c-MET positive and K/NRAS WT mCRC and c-MET positive HNSCC patients | |
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
Maximum Eligible Age: | N/A |
Minimum Eligible Age: | 18 Years |
Eligible Gender: | All |
Healthy Volunteers: | No |
Primary Outcome Measures
Measure: | Incidence of Dose Limiting Toxicities (DLTs) |
Time Frame: | during Cycle 1 and up to 4 weeks from the time of study treatment start |
Safety Issue: | |
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. |
Secondary Outcome Measures
Measure: | 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 |
Safety Issue: | |
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 |
Measure: | Overall Response Rate |
Time Frame: | Every 8 weeks from cycle 1, day 1 until the end of study for up to 3 years |
Safety Issue: | |
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. |
Measure: | Overall Survival |
Time Frame: | Every 12 weeks until the end of study for up to 3 years |
Safety Issue: | |
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. |
Measure: | 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 |
Safety Issue: | |
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. |
Measure: | Severity of Adverse Events (AEs)/Serious Adverse Events (SAEs) |
Time Frame: | From Cycle 1 Day 1 until treatment discontinuation for up to 2 years |
Safety Issue: | |
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 |
Measure: | Frequency of dose treatment interruptions and reductions |
Time Frame: | From Cycle 1 Day 1 until treatment discontinuation for up to 2 years |
Safety Issue: | |
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 |
Measure: | Progression Free Survival |
Time Frame: | Every 8 weeks from C1D1 until the end of study for up to 3 years |
Safety Issue: | |
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. |
Details
Phase: | Phase 1 |
Primary Purpose: | Interventional |
Overall Status: | Terminated |
Lead Sponsor: | Novartis Pharmaceuticals |
Trial 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
Last Updated
January 22, 2019