NCT01280643

Combination Chemotherapy and Cetuximab or Bevacizumab in Treating Patients With Metastatic Colorectal Cancer

An Exploratory Study of Chemotherapy for Metastatic Colorectal Cancer Based Upon Thymidine Phosphorylase Expression, KRAS and BRAF Mutation Status, and ERCC1 Expression

• Status: Terminated
• Phase: N/A
• Study type: Interventional
• Enrollment: 3 (actual)
• Sponsor: Fox Chase Cancer Center · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

RATIONALE: Drugs used in chemotherapy, such as fluorouracil, leucovorin calcium, oxaliplatin, capecitabine, and irinotecan hydrochloride, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) and giving the drugs in different combinations may kill more tumor cells. Monoclonal antibodies, such as bevacizumab and cetuximab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Giving combination chemotherapy together with bevacizumab or cetuximab may kill more tumor cells. PURPOSE:To evaluate the use of standard (KRAS) and experimental (thymidine phosphorylase, ERCC1 and BRAF) tumor testing can aid in selecting chemotherapy regimens

Detailed description

PRIMARY OBJECTIVES: I. To evaluate the feasibility, as defined by completion of three specific marker assays and generation of clinically meaningful endpoints, of selecting treatment regimen components based on biologic tumor characteristics in chemotherapy-naïve patients with metastatic colorectal cancer. SECONDARY OBJECTIVES: I. To investigate the response rate associated with genotype/phenotype guided therapy using Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. II. To investigate the time to failure of treatment strategy associated with genotype/phenotype guided therapy, defined as the time from initiation of investigational treatment strategy until death, disease progression, initiation of a new therapeutic agent, or disease progression while on a partial or complete treatment holiday. III. To investigate the progression-free survival associated with genotype/phenotype guided therapy, defined as the time from enrollment to time of progression of disease or death. OUTLINE: Patients are assigned to treatment groups based on marker assay results. ARM A: TP-/uncertain, KRAS and BRAF wild-type, ERCC1 high ARM B: TP-/uncertain, KRAS and BRAF wild-type, ERCC1 low/uncertain ARM C: TP-/uncertain, KRAS or BRAF mutant/uncertain, ERCC1 high ARM D: TP-/uncertain, KRAS or BRAF mutant/uncertain, ERCC1 low/uncertain ARM E: TP+, KRAS and BRAF wild-type, ERCC1 high ARM F: TP+, KRAS and BRAF wild-type, ERCC1 low/uncertain ARM G: TP+, KRAS or BRAF mutant/uncertain, ERCC1 high ARM H: TP+, KRAS or BRAF mutant/uncertain, ERCC1 low/uncertain ARM I: TP uninterpretable, KRAS or BRAF uninterpretable, ERCC1 uninterpretable KRAS testing is standard of care in patients with metastatic colorectal cancer; tymidine phosphorylase, ERCC1 and BRAF testing assays are still experimental. Courses in arms A-D and arm I repeat every 28 days and courses in arms E-H repeat every 21 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up every 3 months for 18 months.

Conditions

• Metastatic Colorectal Cancer

Interventions

Type	Name	Description
DRUG	fluorouracil	Given IV
DRUG	leucovorin calcium	Given IV
DRUG	oxaliplatin	Given IV
DRUG	irinotecan hydrochloride	Given IV
BIOLOGICAL	bevacizumab	Given IV
BIOLOGICAL	cetuximab	Given IV
DRUG	capecitabine	Given PO
GENETIC	mutation analysis	Correlative studies
GENETIC	gene expression analysis	Correlative studies
OTHER	laboratory biomarker analysis	Correlative studies
OTHER	immunohistochemistry staining method	Correlative studies
GENETIC	nucleic acid sequencing	Correlative studies
GENETIC	protein expression analysis	Correlative studies
GENETIC	polymerase chain reaction	Correlative studies
GENETIC	DNA analysis	Correlative studies

Timeline

• Start date: 2010-03-01
• Primary completion: 2013-07-01
• Completion: 2014-05-01
• First posted: 2011-01-21
• Last updated: 2021-03-15
• Results posted: 2021-03-15

Locations

1 site across 1 country: United States