Clinical trial NCT01280643
Conditions: Metastatic Colorectal Cancer
Keywords: stage IVA colon cancer stage IVA rectal cancer stage IVB colon cancer stage IVB rectal cancer
Sponsor: Fox Chase Cancer Center
Start date: 2010-03-01; Completion date: 2014-05-01
Enrollment: 3 participants; Allocation: NON_RANDOMIZED; Intervention model: PARALLEL

Brief 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.

Arms: arm 1: Patients receive FOLFIRI (FOLolinic acid (leucovorin) Fluorouracil (5-FU) IRInotecan (irinotecan)) chemotherapy comprising fluorouracil intravenously (IV) over 46 hours continuously, leucovorin calcium IV over 2 hours, and irinotecan hydrochloride IV over 90 minutes on days 1 and 15. Patients also receive cetuximab IV over 60-120 minutes on days 1 and 8. arm 2: Patients receive FOLFOX (FOL- Folinic acid (leucovorin) F - Fluorouracil (5-FU) OX - Oxaliplatin (Eloxatin)) chemotherapy comprising fluorouracil IV over 46 hours continuously on day 1 and leucovorin calcium IV over 2 hours and oxaliplatin IV over 2 hours on days 1 and 15. Patients also receive cetuximab IV over 60-120 minutes on days 1 and 8. arm 3: Patients receive FOLFIRI chemotherapy as in Arm A and bevacizumab IV over 30-90 minutes on days 1 and 15. arm 4: Patients receive FOLFOX chemotherapy as in Arm B and bevacizumab IV over 30-90 minutes on days 1 and 15. arm 5: Patients receive CapeIRI (Capecitabine and Irinotecan) chemotherapy comprising capecitabine orally (PO) twice daily (BID) on days 1-14 and irinotecan hydrochloride IV over 90 minutes on days 1 and 8. Patients also receive cetuximab IV over 60-120 minutes on days 1 and 8. arm 6: Patients receive CapeOX (capecitabine (Xeloda) and oxaliplatin (Eloxatin)) chemotherapy comprising capecitabine PO BID on days 1-14 and oxaliplatin IV over 2 hours on day 1. Patients also receive cetuximab IV over 60-120 minutes on days 1 and 8. arm 7: Patients receive CapeIRI chemotherapy as in Arm E and bevacizumab IV over 30-90 minutes on day 1. arm 8: Patients receive CapeOX chemotherapy as in Arm F and bevacizumab IV over 30-90 minutes on day 1. arm 9: Patients receive treatment as in Arm D.
Interventions: intervention 1: fluorouracil intervention 2: leucovorin calcium intervention 3: oxaliplatin intervention 4: irinotecan hydrochloride intervention 5: bevacizumab intervention 6: cetuximab intervention 7: capecitabine intervention 8: mutation analysis intervention 9: gene expression analysis intervention 10: laboratory biomarker analysis intervention 11: immunohistochemistry staining method intervention 12: nucleic acid sequencing intervention 13: protein expression analysis intervention 14: polymerase chain reaction intervention 15: DNA analysis
Intervention descriptions: intervention 1: Given IV intervention 2: Given IV intervention 3: Given IV intervention 4: Given IV intervention 5: Given IV intervention 6: Given IV intervention 7: Given PO intervention 8: Correlative studies intervention 9: Correlative studies intervention 10: Correlative studies intervention 11: Correlative studies intervention 12: Correlative studies intervention 13: Correlative studies intervention 14: Correlative studies intervention 15: Correlative studies

Protocol documents: