Study of Tivantinib (ARQ 197) Plus Cetuximab in EGFR Inhibitor-Resistant MET High Subjects

Colorectal Cancer Metastatic Clinical Trial

Official title: A Single-Arm Phase II Study of Tivantinib (ARQ 197) Plus Cetuximab in EGFR Inhibitor-Resistant MET High Subjects With Locally Advanced or Metastatic Colorectal Cancer With Wild-Type KRAS

Status Completed

Clinical Trial 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.

Clinical Trial 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. ;

Related Conditions & MeSH terms

• C-met Overexpression
• Colorectal Cancer Metastatic
• Colorectal Neoplasms

• NCT number: NCT01892527
• Study type: Interventional
• Source: Istituto Clinico Humanitas
• Status: Completed
• Phase: Phase 2
• Start date: March 2013
• Completion date: March 2017