Study of Tivantinib (ARQ 197) Plus Cetuximab in EGFR Inhibitor-Resistant MET High Subjects
Condition: Colorectal Cancer Metastatic; C-met Overexpression
MeSH terms: Colorectal Neoplasms
Study type: Interventional
Phase: Phase 2

Summary: 
      This is a single-arm, Simon 2-stage, phase 2 clinical study conducted in subjects with
      advanced or metastatic colorectal cancer who have previously received ≥ 1 prior line of
      systemic therapies and are resistant to EGFR inhibitor (cetuximab or panitumumab).

      This trial will be conducted to determine objective response rate (ORR), progression-free
      survival (PFS) and overall-survival (OS) of cetuximab plus tivantinib in patients with
      wild-type KRAS CRC that is resistant to anti-EGFR antibody treatment (cetuximab or
      panitumumab) and shows overexpression of cMET.
    

Detailed description: 
      This is a single-arm, Simon 2-stage, phase 2 clinical study conducted in subjects with
      advanced or metastatic colorectal cancer who have received ≥1 prior line of systemic
      therapies and are resistant to EGFR inhibitor (cetuximab or panitumumab). Fresh tumor tissue
      is needed for the MET testing, thus a biopsy will be required to participate in this trial.
      In a minor percentage of subjects archival tumor tissue could be acceptable for this
      analysis.Eligible subjects will be treated with tivantinib (ARQ 197) at a dose of 360 mg
      twice daily (a total daily dose of 720 mg) orally in a continuous manner and cetuximab
      (Erbitux) at a dose of 500 mg/mq i.v. every 2 weeks. The overall treatment period will be
      divided into continuous 28 days cycles without treatment interruption. Disease status and
      tumor response will be assessed per modified Response Evaluation Criteria In Solid Tumors
      (RECIST) criteria version 1.1 at screening (within 4 weeks before the first scheduled dose of
      study drug), in 8 weeks intervals while the subjects are on treatment or as clinically
      indicated until progression of disease, withdrawal of consent, death, or lost to follow-up.
      Tumor measurement will also be performed during the end of treatment visit if not done within
      the previous 8 weeks. Subjects with progressive disease at any time during the treatment
      period will discontinue study treatment. Subjects with stable disease (SD), complete response
      (CR) and partial response (PR) will stay on treatment until disease progression and/or
      unacceptable toxicity and/or withdrawal of consent is documented. CR and PR must be confirmed
      no sooner than 4 weeks after the initial observation. After discontinuation from study
      treatment during the follow-up period, survival status will be obtained by phone every 3
      months until the subject dies, withdraws consent from study, or is lost to follow-up, for a
      maximum of 12 months.
    

Intervention name(s): Tivantinib (ARQ197)
Intervention type(s): Drug
Intervention description(s): Eligible subjects will be treated with tivantinib (ARQ 197) at a dose of 360 mg twice daily (a total daily dose of 720 mg) orally in a continuous manner and cetuximab (Erbitux) at a dose of 500 mg/mq i.v. every 2 weeks.
Other intervention name(s): Cetuximab
Intervention MeSH terms: Cetuximab
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Colorectal Cancer Metastatic; wild type KRAS; C-met overexpression; Tivantinib; Cetuximab