Recruitment

Recruitment Status
Unknown status
Estimated Enrollment
41

Inclusion Criterias

Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 2.
All subjects must express the wild-type form of the gene KRAS. Previously existing KRAS mutation status from an accredited local laboratory will be accepted.
Fresh tumor biopsy tissue must be available for molecular sequencing and biomarker expression in >70% of patients. If prior radiotherapy, tissue biopsy must be outside radiotherapy field. In a minor percentage of patients (<30%) archival tumor tissue could be considered acceptable for molecular sequencing and biomarker expression.
...
Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 2.
All subjects must express the wild-type form of the gene KRAS. Previously existing KRAS mutation status from an accredited local laboratory will be accepted.
Fresh tumor biopsy tissue must be available for molecular sequencing and biomarker expression in >70% of patients. If prior radiotherapy, tissue biopsy must be outside radiotherapy field. In a minor percentage of patients (<30%) archival tumor tissue could be considered acceptable for molecular sequencing and biomarker expression.
Male and female subjects of child-bearing potential must agree to use double-barrier contraceptive measures, oral contraception, or avoidance of intercourse during the study and for 90 days after last investigational drug dose received. 11. All female subjects of childbearing potential must each have a negative pregnancy test (serum or urine) result before initiating study treatment.
Patients must be MET High testing by IHC (IHC 2+ or 3+ in ≥50% of tumor cells) analyzed by Ventana Test Kit.
Resolution of any toxic effects of prior therapy to NCI CTCAE, Version 4.0, grade ≤ 1 (with the exception of alopecia and grade ≤ 2 neuropathy).
Subjects with surgically unresectable locally advanced or metastatic disease who have received ≥ 1 prior line of systemic therapies for advanced or metastatic disease. The last treatment regimen must include EGFR inhibitor (cetuximab or panitumumab) on which the patient had a best response as CR or PR or SD, and must have either progressed on or after EGFR inhibitor based therapy within 3 months before enrollment. Subjects must have radiologically documented disease progression prior to enrollment.
Measurable disease according to RECIST criteria, Version 1.1.
Male or female ≥ 18 years of age.

Summary

Conditions
  • C-met Overexpression
  • Colorectal Cancer Metastatic
Type
Interventional
Phase
Phase 2
Design
  • Allocation: N/A
  • Intervention Model: Single Group Assignment
  • Masking: None (Open Label)
  • Primary Purpose: Treatment

Participation Requirements

Age
Between 18 years and 80 years
Gender
Both males and females

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...

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.

Inclusion Criterias

Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 2.
All subjects must express the wild-type form of the gene KRAS. Previously existing KRAS mutation status from an accredited local laboratory will be accepted.
Fresh tumor biopsy tissue must be available for molecular sequencing and biomarker expression in >70% of patients. If prior radiotherapy, tissue biopsy must be outside radiotherapy field. In a minor percentage of patients (<30%) archival tumor tissue could be considered acceptable for molecular sequencing and biomarker expression.
...
Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 2.
All subjects must express the wild-type form of the gene KRAS. Previously existing KRAS mutation status from an accredited local laboratory will be accepted.
Fresh tumor biopsy tissue must be available for molecular sequencing and biomarker expression in >70% of patients. If prior radiotherapy, tissue biopsy must be outside radiotherapy field. In a minor percentage of patients (<30%) archival tumor tissue could be considered acceptable for molecular sequencing and biomarker expression.
Male and female subjects of child-bearing potential must agree to use double-barrier contraceptive measures, oral contraception, or avoidance of intercourse during the study and for 90 days after last investigational drug dose received. 11. All female subjects of childbearing potential must each have a negative pregnancy test (serum or urine) result before initiating study treatment.
Patients must be MET High testing by IHC (IHC 2+ or 3+ in ≥50% of tumor cells) analyzed by Ventana Test Kit.
Resolution of any toxic effects of prior therapy to NCI CTCAE, Version 4.0, grade ≤ 1 (with the exception of alopecia and grade ≤ 2 neuropathy).
Subjects with surgically unresectable locally advanced or metastatic disease who have received ≥ 1 prior line of systemic therapies for advanced or metastatic disease. The last treatment regimen must include EGFR inhibitor (cetuximab or panitumumab) on which the patient had a best response as CR or PR or SD, and must have either progressed on or after EGFR inhibitor based therapy within 3 months before enrollment. Subjects must have radiologically documented disease progression prior to enrollment.
Measurable disease according to RECIST criteria, Version 1.1.
Male or female ≥ 18 years of age.

Locations

Rozzano, Milano, 20089
Rozzano, Milano, 20089

Tracking Information

NCT #
NCT01892527
Collaborators
Not Provided
Investigators
Study Chair: Lorenza Rimassa, MD Istituto Clinico Humanitas