Combination Chemotherapy and Cetuximab or Bevacizumab in Treating Patients With Metastatic Colorectal Cancer
NCT ID: NCT01280643
Last Updated: 2021-03-15
Study Results
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View full resultsBasic Information
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TERMINATED
NA
3 participants
INTERVENTIONAL
2010-03-31
2014-05-31
Brief Summary
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PURPOSE:To evaluate the use of standard (KRAS) and experimental (thymidine phosphorylase, ERCC1 and BRAF) tumor testing can aid in selecting chemotherapy regimens
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Detailed Description
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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
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Study Design
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NON_RANDOMIZED
PARALLEL
TREATMENT
NONE
Study Groups
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Arm A
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.
fluorouracil
Given IV
leucovorin calcium
Given IV
irinotecan hydrochloride
Given IV
cetuximab
Given IV
mutation analysis
Correlative studies
gene expression analysis
Correlative studies
laboratory biomarker analysis
Correlative studies
immunohistochemistry staining method
Correlative studies
nucleic acid sequencing
Correlative studies
protein expression analysis
Correlative studies
polymerase chain reaction
Correlative studies
DNA analysis
Correlative studies
Arm B
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.
fluorouracil
Given IV
leucovorin calcium
Given IV
oxaliplatin
Given IV
cetuximab
Given IV
mutation analysis
Correlative studies
gene expression analysis
Correlative studies
laboratory biomarker analysis
Correlative studies
immunohistochemistry staining method
Correlative studies
nucleic acid sequencing
Correlative studies
protein expression analysis
Correlative studies
polymerase chain reaction
Correlative studies
DNA analysis
Correlative studies
Arm C
Patients receive FOLFIRI chemotherapy as in Arm A and bevacizumab IV over 30-90 minutes on days 1 and 15.
fluorouracil
Given IV
leucovorin calcium
Given IV
irinotecan hydrochloride
Given IV
bevacizumab
Given IV
mutation analysis
Correlative studies
gene expression analysis
Correlative studies
laboratory biomarker analysis
Correlative studies
immunohistochemistry staining method
Correlative studies
nucleic acid sequencing
Correlative studies
protein expression analysis
Correlative studies
polymerase chain reaction
Correlative studies
DNA analysis
Correlative studies
Arm D
Patients receive FOLFOX chemotherapy as in Arm B and bevacizumab IV over 30-90 minutes on days 1 and 15.
fluorouracil
Given IV
leucovorin calcium
Given IV
oxaliplatin
Given IV
bevacizumab
Given IV
mutation analysis
Correlative studies
gene expression analysis
Correlative studies
laboratory biomarker analysis
Correlative studies
immunohistochemistry staining method
Correlative studies
nucleic acid sequencing
Correlative studies
protein expression analysis
Correlative studies
polymerase chain reaction
Correlative studies
DNA analysis
Correlative studies
Arm E
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.
irinotecan hydrochloride
Given IV
cetuximab
Given IV
capecitabine
Given PO
mutation analysis
Correlative studies
gene expression analysis
Correlative studies
laboratory biomarker analysis
Correlative studies
immunohistochemistry staining method
Correlative studies
nucleic acid sequencing
Correlative studies
protein expression analysis
Correlative studies
polymerase chain reaction
Correlative studies
DNA analysis
Correlative studies
Arm F
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.
oxaliplatin
Given IV
cetuximab
Given IV
capecitabine
Given PO
mutation analysis
Correlative studies
gene expression analysis
Correlative studies
laboratory biomarker analysis
Correlative studies
immunohistochemistry staining method
Correlative studies
nucleic acid sequencing
Correlative studies
protein expression analysis
Correlative studies
polymerase chain reaction
Correlative studies
DNA analysis
Correlative studies
ARM G
Patients receive CapeIRI chemotherapy as in Arm E and bevacizumab IV over 30-90 minutes on day 1.
irinotecan hydrochloride
Given IV
bevacizumab
Given IV
capecitabine
Given PO
mutation analysis
Correlative studies
gene expression analysis
Correlative studies
laboratory biomarker analysis
Correlative studies
immunohistochemistry staining method
Correlative studies
nucleic acid sequencing
Correlative studies
protein expression analysis
Correlative studies
polymerase chain reaction
Correlative studies
DNA analysis
Correlative studies
Arm H
Patients receive CapeOX chemotherapy as in Arm F and bevacizumab IV over 30-90 minutes on day 1.
oxaliplatin
Given IV
bevacizumab
Given IV
capecitabine
Given PO
mutation analysis
Correlative studies
gene expression analysis
Correlative studies
laboratory biomarker analysis
Correlative studies
immunohistochemistry staining method
Correlative studies
nucleic acid sequencing
Correlative studies
protein expression analysis
Correlative studies
polymerase chain reaction
Correlative studies
DNA analysis
Correlative studies
Arm I
Patients receive treatment as in Arm D.
fluorouracil
Given IV
leucovorin calcium
Given IV
oxaliplatin
Given IV
bevacizumab
Given IV
mutation analysis
Correlative studies
gene expression analysis
Correlative studies
laboratory biomarker analysis
Correlative studies
immunohistochemistry staining method
Correlative studies
nucleic acid sequencing
Correlative studies
protein expression analysis
Correlative studies
polymerase chain reaction
Correlative studies
DNA analysis
Correlative studies
Interventions
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fluorouracil
Given IV
leucovorin calcium
Given IV
oxaliplatin
Given IV
irinotecan hydrochloride
Given IV
bevacizumab
Given IV
cetuximab
Given IV
capecitabine
Given PO
mutation analysis
Correlative studies
gene expression analysis
Correlative studies
laboratory biomarker analysis
Correlative studies
immunohistochemistry staining method
Correlative studies
nucleic acid sequencing
Correlative studies
protein expression analysis
Correlative studies
polymerase chain reaction
Correlative studies
DNA analysis
Correlative studies
Other Intervention Names
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Eligibility Criteria
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Inclusion Criteria
* 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
Exclusion Criteria
* 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
18 Years
ALL
No
Sponsors
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National Cancer Institute (NCI)
NIH
Fox Chase Cancer Center
OTHER
Responsible Party
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Principal Investigators
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Crystal Denlinger
Role: PRINCIPAL_INVESTIGATOR
Fox Chase Cancer Center
Locations
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Fox Chase Cancer Center
Philadelphia, Pennsylvania, United States
Countries
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Other Identifiers
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NCI-2011-00046
Identifier Type: REGISTRY
Identifier Source: secondary_id
IRB 09-033
Identifier Type: -
Identifier Source: org_study_id
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