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

NCT02205398 | Terminated Phase 1 FDA Drug

• 2 other identifiers: CINC280X21042014-000579-20
• Study Type: interventional
• Target: 13
• Locations: 7 countries
• Sites: 15

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.

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

Outcome Measures

Primary Outcomes (1)

• 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

Secondary Outcomes (7)

• Frequency of Adverse Events (AEs)/Serious Adverse Events (SAEs)

  During Cycle 1 Day 1 (C1D1) until treatment discontinuation for up to 2 years

• Overall Response Rate

  Every 8 weeks from cycle 1, day 1 until the end of study for up to 3 years

• Overall Survival

  Every 12 weeks until the end of study for up to 3 years

• 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

• Severity of Adverse Events (AEs)/Serious Adverse Events (SAEs)

  From Cycle 1 Day 1 until treatment discontinuation for up to 2 years

Study Arms (1)

c-MET positive mCRC and HNSCC

EXPERIMENTAL

c-MET positive and K/NRAS WT mCRC and c-MET positive HNSCC patients

Drug: INC280; Drug: cetuximab

Interventions

INC280 DRUG

c-MET positive mCRC and HNSCC

cetuximab DRUG

c-MET positive mCRC and HNSCC

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (15)

Massachusetts General Hospital Head & Neck

Boston, Massachusetts, 02114, United States

Location

Memorial Sloan Kettering MSKCC NY

New York, New York, 10017, United States

Location

University of Utah / Huntsman Cancer Institute Onc Dept

Salt Lake City, Utah, 84103, United States

Location

Novartis Investigative Site

Leuven, 3000, Belgium

Location

Novartis Investigative Site

Toronto, Ontario, M5G 1X6, Canada

Location

Novartis Investigative Site

Lyon, 69373, France

Location

Novartis Investigative Site

Toulouse, 31059, France

Location

Novartis Investigative Site

Essen, 45147, Germany

Location

Novartis Investigative Site

Würzburg, 97080, Germany

Location

Novartis Investigative Site

Ancona, AN, 60126, Italy

Location

Novartis Investigative Site

Milan, MI, 20162, Italy

Location

Novartis Investigative Site

Barcelona, Catalonia, 08003, Spain

Location

Novartis Investigative Site

Barcelona, Catalonia, 08035, Spain

Location

Novartis Investigative Site

L'Hospitalet de Llobregat, Catalonia, 08907, Spain

Location

Novartis Investigative Site

Valencia, Valencia, 46010, Spain

Location

Related Publications (1)

• 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.

  PMID: 32410080 DERIVED

MeSH Terms

Conditions

Squamous Cell Carcinoma of Head and Neck; Colorectal Neoplasms; Carcinoma, Squamous Cell; Neoplasms; Laryngeal Diseases; Rectal Neoplasms

Interventions

capmatinib; Cetuximab

Condition Hierarchy (Ancestors)

Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Head and Neck Neoplasms; Neoplasms by Site; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases; Neoplasms, Squamous Cell; Respiratory Tract Diseases; Otorhinolaryngologic Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 25, 2014
• First Posted: July 31, 2014
• Study Start: July 28, 2014
• Primary Completion: January 20, 2017
• Study Completion: January 20, 2017
• Last Updated: January 22, 2019

Record last verified: 2019-01

Locations

IT (2); ES (4); DE (2); FR (2); US (3); CA (1); BE (1)