Clinical Trials /

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

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.

Related Conditions:
  • Colorectal Carcinoma
  • Head and Neck Squamous Cell Carcinoma
Recruiting Status:

Terminated

Phase:

Phase 1

Trial Eligibility

Document

Study of Safety and Efficacy of INC280 and <span class="go-doc-concept go-doc-intervention">Cetuximab</span>, in Adult c-<span class="go-doc-concept go-doc-biomarker">MET</span> Positive mCRC and HNSCC Patients After Progression on <span class="go-doc-concept go-doc-intervention">Cetuximab</span> or <span class="go-doc-concept go-doc-intervention">Panitumumab</span> Therapy

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

    NCT ID: NCT02205398

    ORG ID: CINC280X2104

    NCI ID: 2014-000579-20

    Trial Conditions

    Squamous Cell Carcinoma of Head and Neck,

    Metastatic Colorectal Cancer

    Trial Interventions

    Drug Synonyms Arms
    INC280 c-MET positive mCRC and HNSCC
    cetuximab c-MET positive mCRC and HNSCC

    Trial Purpose

    This is 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
    will be explored in c-MET positive mCRC and HNSCC patients whose disease progressed on
    cetuximab or panitumumab treatment. The dose escalation part will be guided by a Bayesian
    Logistic Regression Model with overdose control. At MTD/RDE, additional mCRC and HNSCC
    patients who have progressed on cetuximab or panitumumab treatment will 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 will receive INC280 on a continuous bid
    dosing regimen and cetuximab every week. A treatment cycle is defined as 28 days with no
    scheduled break between cycles.

    Detailed Description

    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 INC280, cetuximab

    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 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 or EGFR inhibitors (with the exception of the last
    treatment)

    - 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

    Other protocol-defined inclusion/exclusion criteria may apply NVS Definition: List only
    the main study specific inclusion/exclusion criteria that patients will understand.

    Note: DO NOT cut/paste directly from the protocol.

    Do not include age and gender as part of this field. Age and gender are indicated in the 2
    fields below.

    Always include statement "Other protocol-defined inclusion/exclusion criteria may apply"
    at the end of this section.

    Examples:

    Inclusion criteria:

    Patients within 7- 42 days of an acute myocardial infarction associated with left
    ventricular systolic dysfunction Qualifying Echocardiogram at Visit 1

    Exclusion criteria:

    Presence of clinically overt heart failure Percutaneous coronary intervention (PCI) less
    than 24 hours before randomization previous treatment with aliskiren

    Other protocol-defined inclusion/exclusion criteria may apply.

    Minimum Eligible Age: 18 Years

    Maximum Eligible Age: N/A

    Eligible Gender: Both

    Primary Outcome Measures

    Incidence of Dose Limiting Toxicities (DLTs)

    Secondary Outcome Measures

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

    Overall Response Rate

    Overall Survival

    Time versus plasma concentration profiles and basic PK parameters of INC280

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

    Frequency of dose treatment interruptions and reductions

    Progression Free Survival

    Trial Keywords

    INC280,

    c-MET inhibitor,

    cetuximab,

    metastatic colorectal cancer,

    head and neck,

    squamous cell carcinoma,

    resistance to cetuximab/panitumumab