Clinical trial NCT02205398: 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
Overall status: TERMINATED
Phase: PHASE1
Conditions: 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
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2014-07-31
Enrollment: 13
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


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

Primary outcomes:
measure: Incidence of Dose Limiting Toxicities (DLTs)
timeFrame: during Cycle 1 and up to 4 weeks from the time of study treatment start
Secondary outcomes:
measure: Frequency of Adverse Events (AEs)/Serious Adverse Events (SAEs)
timeFrame: During Cycle 1 Day 1 (C1D1) until treatment discontinuation for up to 2 years
measure: Overall Response Rate
timeFrame: Every 8 weeks from cycle 1, day 1 until the end of study for up to 3 years
measure: Overall Survival
timeFrame: Every 12 weeks until the end of study for up to 3 years
measure: Time versus plasma concentration profiles and basic PK parameters of INC280
timeFrame: during the first 4 Cycles of treatment or up to 16 weeks from the time of study treatment start
measure: Severity of Adverse Events (AEs)/Serious Adverse Events (SAEs)
timeFrame: From Cycle 1 Day 1 until treatment discontinuation for up to 2 years
measure: Frequency of dose treatment interruptions and reductions
timeFrame: From Cycle 1 Day 1 until treatment discontinuation for up to 2 years
measure: Progression Free Survival
timeFrame: Every 8 weeks from C1D1 until the end of study for up to 3 years
Other outcomes:
Locations:
city: Boston
country: United States
facility: Massachusetts General Hospital Head & Neck
state: Massachusetts
city: New York
country: United States
facility: Memorial Sloan Kettering MSKCC NY
state: New York
city: Salt Lake City
country: United States
facility: University of Utah / Huntsman Cancer Institute Onc Dept
state: Utah
city: Leuven
country: Belgium
facility: Novartis Investigative Site
city: Toronto
country: Canada
facility: Novartis Investigative Site
state: Ontario
city: Lyon Cedex
country: France
facility: Novartis Investigative Site
city: Toulouse Cedex 9
country: France
facility: Novartis Investigative Site
city: Essen
country: Germany
facility: Novartis Investigative Site
city: Wuerzburg
country: Germany
facility: Novartis Investigative Site
city: Ancona
country: Italy
facility: Novartis Investigative Site
state: AN
city: Milano
country: Italy
facility: Novartis Investigative Site
state: MI
city: Barcelona
country: Spain
facility: Novartis Investigative Site
state: Catalunya
city: Barcelona
country: Spain
facility: Novartis Investigative Site
state: Catalunya
city: Hospitalet de LLobregat
country: Spain
facility: Novartis Investigative Site
state: Catalunya
city: Valencia
country: Spain
facility: Novartis Investigative Site
state: Comunidad Valenciana
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References:
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.