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

NCT01280643 | Terminated Results DMC

• 2 other identifiers: IRB 09-033NCI-2011-00046
• Study Type: interventional
• Target: 3
• Locations: 1 country
• Sites: 1

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

Conditions

Metastatic Colorectal Cancer

Keywords

stage IVA colon cancer; stage IVA rectal cancer; stage IVB colon cancer; stage IVB rectal cancer

Outcome Measures

Primary Outcomes (1)

• Feasibility, Defined as a Sufficient Proportion of Subjects Having Available Tissue and an Acceptable Composite Assay Success Rate Among Tested Subjects

  Over 21 months

Secondary Outcomes (3)

• Best Overall Response Via RECIST

  Over 21 months

• Time to Failure of Treatment Strategy

  Over 21 months

• Progression-free Survival

  Over 21 months

Study Arms (9)

Arm A

EXPERIMENTAL

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.

Drug: fluorouracil; Drug: leucovorin calcium; Drug: irinotecan hydrochloride; Biological: cetuximab; Genetic: mutation analysis; Genetic: gene expression analysis; Other: laboratory biomarker analysis; Other: immunohistochemistry staining method; Genetic: nucleic acid sequencing; Genetic: protein expression analysis; Genetic: polymerase chain reaction; Genetic: DNA analysis

Arm B

EXPERIMENTAL

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.

Drug: fluorouracil; Drug: leucovorin calcium; Drug: oxaliplatin; Biological: cetuximab; Genetic: mutation analysis; Genetic: gene expression analysis; Other: laboratory biomarker analysis; Other: immunohistochemistry staining method; Genetic: nucleic acid sequencing; Genetic: protein expression analysis; Genetic: polymerase chain reaction; Genetic: DNA analysis

Arm C

EXPERIMENTAL

Patients receive FOLFIRI chemotherapy as in Arm A and bevacizumab IV over 30-90 minutes on days 1 and 15.

Drug: fluorouracil; Drug: leucovorin calcium; Drug: irinotecan hydrochloride; Biological: bevacizumab; Genetic: mutation analysis; Genetic: gene expression analysis; Other: laboratory biomarker analysis; Other: immunohistochemistry staining method; Genetic: nucleic acid sequencing; Genetic: protein expression analysis; Genetic: polymerase chain reaction; Genetic: DNA analysis

Arm D

EXPERIMENTAL

Patients receive FOLFOX chemotherapy as in Arm B and bevacizumab IV over 30-90 minutes on days 1 and 15.

Drug: fluorouracil; Drug: leucovorin calcium; Drug: oxaliplatin; Biological: bevacizumab; Genetic: mutation analysis; Genetic: gene expression analysis; Other: laboratory biomarker analysis; Other: immunohistochemistry staining method; Genetic: nucleic acid sequencing; Genetic: protein expression analysis; Genetic: polymerase chain reaction; Genetic: DNA analysis

Arm E

EXPERIMENTAL

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.

Drug: irinotecan hydrochloride; Biological: cetuximab; Drug: capecitabine; Genetic: mutation analysis; Genetic: gene expression analysis; Other: laboratory biomarker analysis; Other: immunohistochemistry staining method; Genetic: nucleic acid sequencing; Genetic: protein expression analysis; Genetic: polymerase chain reaction; Genetic: DNA analysis

Arm F

EXPERIMENTAL

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.

Drug: oxaliplatin; Biological: cetuximab; Drug: capecitabine; Genetic: mutation analysis; Genetic: gene expression analysis; Other: laboratory biomarker analysis; Other: immunohistochemistry staining method; Genetic: nucleic acid sequencing; Genetic: protein expression analysis; Genetic: polymerase chain reaction; Genetic: DNA analysis

ARM G

EXPERIMENTAL

Patients receive CapeIRI chemotherapy as in Arm E and bevacizumab IV over 30-90 minutes on day 1.

Drug: irinotecan hydrochloride; Biological: bevacizumab; Drug: capecitabine; Genetic: mutation analysis; Genetic: gene expression analysis; Other: laboratory biomarker analysis; Other: immunohistochemistry staining method; Genetic: nucleic acid sequencing; Genetic: protein expression analysis; Genetic: polymerase chain reaction; Genetic: DNA analysis

Arm H

EXPERIMENTAL

Patients receive CapeOX chemotherapy as in Arm F and bevacizumab IV over 30-90 minutes on day 1.

Drug: oxaliplatin; Biological: bevacizumab; Drug: capecitabine; Genetic: mutation analysis; Genetic: gene expression analysis; Other: laboratory biomarker analysis; Other: immunohistochemistry staining method; Genetic: nucleic acid sequencing; Genetic: protein expression analysis; Genetic: polymerase chain reaction; Genetic: DNA analysis

Arm I

EXPERIMENTAL

Patients receive treatment as in Arm D.

Drug: fluorouracil; Drug: leucovorin calcium; Drug: oxaliplatin; Biological: bevacizumab; Genetic: mutation analysis; Genetic: gene expression analysis; Other: laboratory biomarker analysis; Other: immunohistochemistry staining method; Genetic: nucleic acid sequencing; Genetic: protein expression analysis; Genetic: polymerase chain reaction; Genetic: DNA analysis

Interventions

fluorouracil DRUG

Given IV

Also known as: 5-fluorouracil, 5-Fluracil, 5-FU

Arm A; Arm B; Arm C; Arm D; Arm I

leucovorin calcium DRUG

Given IV

Also known as: CF, CFR, LV

Arm A; Arm B; Arm C; Arm D; Arm I

oxaliplatin DRUG

Given IV

Also known as: 1-OHP, Dacotin, Dacplat, Eloxatin, L-OHP

Arm B; Arm D; Arm F; Arm H; Arm I

irinotecan hydrochloride DRUG

Given IV

Also known as: Campto, Camptosar, CPT-11, irinotecan, U-101440E

ARM G; Arm A; Arm C; Arm E

bevacizumab BIOLOGICAL

Given IV

Also known as: anti-VEGF humanized monoclonal antibody, anti-VEGF monoclonal antibody, Avastin, rhuMAb VEGF

ARM G; Arm C; Arm D; Arm H; Arm I

cetuximab BIOLOGICAL

Given IV

Also known as: C225, C225 monoclonal antibody, IMC-C225, MOAB C225, monoclonal antibody C225

Arm A; Arm B; Arm E; Arm F

capecitabine DRUG

Given PO

Also known as: CAPE, Ro 09-1978/000, Xeloda

ARM G; Arm E; Arm F; Arm H

mutation analysis GENETIC

Correlative studies

ARM G; Arm A; Arm B; Arm C; Arm D; Arm E; Arm F; Arm H; Arm I

gene expression analysis GENETIC

Correlative studies

ARM G; Arm A; Arm B; Arm C; Arm D; Arm E; Arm F; Arm H; Arm I

laboratory biomarker analysis OTHER

Correlative studies

ARM G; Arm A; Arm B; Arm C; Arm D; Arm E; Arm F; Arm H; Arm I

immunohistochemistry staining method OTHER

Correlative studies

Also known as: immunohistochemistry

ARM G; Arm A; Arm B; Arm C; Arm D; Arm E; Arm F; Arm H; Arm I

nucleic acid sequencing GENETIC

Correlative studies

Also known as: Gene Sequencing, Molecular Biology, Nucleic Acid Sequencing

ARM G; Arm A; Arm B; Arm C; Arm D; Arm E; Arm F; Arm H; Arm I

protein expression analysis GENETIC

Correlative studies

ARM G; Arm A; Arm B; Arm C; Arm D; Arm E; Arm F; Arm H; Arm I

polymerase chain reaction GENETIC

Correlative studies

Also known as: PCR

ARM G; Arm A; Arm B; Arm C; Arm D; Arm E; Arm F; Arm H; Arm I

DNA analysis GENETIC

Correlative studies

ARM G; Arm A; Arm B; Arm C; Arm D; Arm E; Arm F; Arm H; Arm I

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients must have histologically confirmed colon or rectal cancer that has metastasized; no biopsy of metastatic site(s) are required if presentation is consistent with metastatic disease
• Available archived tissue block or slides from the primary colon or rectal cancer; approximately 25 slides from the primary tumor tissue are necessary for testing of all markers
• Patients must have measurable disease by RECIST 1.1, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) as \>= 10 mm with computed tomography (CT) scan or clinical exam with calipers; lymph nodes must be 15 mm in shortest dimension as measured on CT scan
• Patients may not have received prior therapy for metastatic colorectal cancer; prior adjuvant therapy (including any of the study agents) is permitted if completed \> 6 months from the initial detection of metastatic disease
• Eastern Cooperative Oncology Group (ECOG) performance status 0-1
• Absolute neutrophil count \>= 1,500/mcL
• Platelets \>= 100,000/mcL
• Total bilirubin =\< 2 X institutional upper limit of normal (ULN)
• Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase \[SGOT\])/ alanine aminotransferase (ALT) (serum glutamic pyruvate transaminase \[SGPT\]) =\< 3 X institutional ULN or =\< 5 X ULN if known liver metastases
• Creatinine clearance \>= 50 mL/min (as calculated by Cockroft and Gault formula)
• Urine protein:creatinine (UPC) ratio \< 1.0 at screening (as calculated from urine protein concentration and urine creatinine concentration); patients with a UPC ratio \>= 1 will undergo a 24-hour urine collection, which must be adequate and demonstrate \< 1 gram in order to participate
• Ability to understand and the willingness to sign a written informed consent document

You may not qualify if:

• Patients who have had previous chemotherapy for metastatic colorectal cancer
• Uncontrolled hypertension (\>150/100 mmHg) despite a stable regimen of anti-hypertensive medication
• History of cardiovascular disease, defined as previous myocardial infarction, cerebrovascular accident, uncontrolled congestive heart failure (New York Heart Association \> Class II), clinically significant ventricular arrhythmia requiring medication, clinically significant peripheral vascular disease, or unstable angina within 6 months of study enrollment
• Underlying neuropathy \>= grade 2
• Serious non-healing wounds, ulcers, or fistulas
• Major surgery, open biopsy, or major traumatic injury within 28 days of registration, or anticipation of need for surgical procedure during course of study, and core biopsy or fine needle aspiration within 7 days of registration; closed biopsy or access port placement is acceptable
• A history of thrombotic or hemorrhagic disorder; patients with elevated international normalized ratio (INR) (2.0 to 3.0) on stable doses of therapeutic anticoagulation are eligible
• Untreated brain metastases; patients with treated brain metastases who have completed radiation therapy, are clinically and radiographically stable, and are off steroid therapy may be enrolled
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to cetuximab, oxaliplatin, capecitabine, or other agents used in the study
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, or psychiatric illness/social situations that would limit compliance with study requirements
• Pregnant women are excluded; breastfeeding should be discontinued if the mother is treated with chemotherapy
• Human Immunodeficiency Virus (HIV)-positive patients on combination antiretroviral therapy are ineligible; appropriate studies will be undertaken in patients receiving combination antiretroviral therapy when indicated
• Patients must not have a history of another neoplasm \< 5 years prior to enrollment, except for non-metastatic, non-melanoma skin cancer or carcinoma in situ of the cervix
• Patients of child-bearing potential who are unwilling or unable to utilize contraceptive measures including barrier contraception

Sponsors & Collaborators

• Fox Chase Cancer Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

Fox Chase Cancer Center

Philadelphia, Pennsylvania, 19111-2497, United States

Location

MeSH Terms

Conditions

Colorectal Neoplasms; Colonic Neoplasms; Rectal Neoplasms

Interventions

Fluorouracil; Leucovorin; Oxaliplatin; Irinotecan; Bevacizumab; Cetuximab; Capecitabine; Gene Expression Profiling; Immunohistochemistry; Base Sequence; Polymerase Chain Reaction

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Intervention Hierarchy (Ancestors)

Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Formyltetrahydrofolates; Tetrahydrofolates; Folic Acid; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Coenzymes; Enzymes and Coenzymes; Coordination Complexes; Organic Chemicals; Camptothecin; Alkaloids; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Genetic Techniques; Investigative Techniques; Histocytochemistry; Cytological Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Histological Techniques; Immunologic Techniques; Molecular Structure; Biochemical Phenomena; Chemical Phenomena; Genetic Structures; Genetic Phenomena; Nucleic Acid Amplification Techniques

Limitations and Caveats

Too few enrolled participants for meaningful analysis. Study closed prematurely due to slow accrual.

Results Point of Contact

• Title: Dr. Crystal Denlinger
• Organization: Fox Chase Cancer Center

crystal.denlinger@fccc.edu

215-214-1676

Study Officials

• Crystal Denlinger

  Fox Chase Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 20, 2011
• First Posted: January 21, 2011
• Study Start: March 1, 2010
• Primary Completion: July 1, 2013
• Study Completion: May 1, 2014
• Last Updated: March 15, 2021
• Results First Posted: March 15, 2021

Record last verified: 2021-02

Locations

US (1)