Irinotecan and Cetuximab With or Without Bevacizumab in Treating Patients With RAS Wild-Type Locally Advanced or Metastatic Colorectal Cancer That Cannot Be Removed by Surgery
BOND-3: A Randomized, Double-Blind, Placebo-Controlled Phase II Trial of Irinotecan, Cetuximab, and Bevacizumab Compared With Irinotecan, Cetuximab, and Placebo in RAS-Wildtype, Irinotecan-Refractory, Metastatic Colorectal Cancer
3 other identifiers
interventional
36
1 country
13
Brief Summary
This randomized phase II trial studies how well irinotecan and cetuximab with or without bevacizumab work in treating patients with RAS wild-type colorectal cancer that has spread to other places in the body (locally advanced/metastatic) and cannot be removed by surgery. Irinotecan may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Immunotherapy with monoclonal antibodies, such as cetuximab and bevacizumab, may help the body?s immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving irinotecan and cetuximab with or without bevacizumab may work betting in treating patients with colorectal cancer.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P25-P50 for phase_2
Started Dec 2014
Longer than P75 for phase_2
13 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
November 13, 2014
CompletedFirst Posted
Study publicly available on registry
November 17, 2014
CompletedStudy Start
First participant enrolled
December 12, 2014
CompletedPrimary Completion
Last participant's last visit for primary outcome
March 20, 2019
CompletedStudy Completion
Last participant's last visit for all outcomes
September 27, 2019
CompletedResults Posted
Study results publicly available
February 28, 2020
CompletedJanuary 31, 2022
August 1, 2019
4.3 years
November 13, 2014
January 31, 2020
January 27, 2022
Conditions
Outcome Measures
Primary Outcomes (2)
Progression-Free Survival (PFS)
The distribution of PFS by group will be estimated using the method of Kaplan-Meier. Median by treatment group with confidence intervals will be estimated based on Kaplan-Meier curves. The hazard ratio (HR) with confidence interval will be estimated based on stratified Cox models (stratified by levels of stratification factors), without and with adjusting for baseline clinical/pathological factors. Progression (PD) is defined according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. PD: Any new lesion or increase by ≥50% of previously involved sites from nadir).
From the date of randomization to the date of 1st documented disease progression or death due to any cause, whichever occurs first, assessed up to 24 months
6-month and 12-month Progression-free Survival (PFS) Rates
The distribution of PFS by group will be estimated using the method of Kaplan-Meier. Six and 12 month PFS rates by treatment group with confidence intervals will be estimated based on Kaplan-Meier curves. The hazard ratio (HR) with confidence interval will be estimated based on stratified Cox models (stratified by levels of stratification factors), without and with adjusting for baseline clinical/pathological factors. Progression (PD) is defined according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. PD: Any new lesion or increase by ≥50% of previously involved sites from nadir).
From the date of randomization to the date of 1st documented disease progression or death due to any cause, whichever occurs first, assessed up to 24 months
Secondary Outcomes (8)
Number of Participants Who Experienced at Least One Grade 3 or Higher Adverse Events
Up to 30 days from last dose of study treatment
Overall Survival (OS)
From randomization to the date of death due to any cause, assessed up to 24 months
12-month, 18-month, and 24-month Overall Survival (OS) Rates
From randomization to the date of death due to any cause, assessed up to 24 months
Disease Control Rate (DCR)
Up to 2 years
Overall Response Rate (ORR)
Up to 2 years
- +3 more secondary outcomes
Other Outcomes (2)
Change in Genotype Concentrations of Prespecified Gene Mutations in Circulating Cell-free Deoxyribonucleic Acid (DNA) (cfDNA)
Baseline up to 2 years
Dynamic Change in Mutation Concentration While the Patient is Receiving Cetuximab Treatment
Baseline up to 2 years
Study Arms (2)
Arm I (cetuximab, bevacizumab, irinotecan)
EXPERIMENTALPatients receive cetuximab IV over 90-120 minutes, bevacizumab IV over 30-90 minutes, and irinotecan IV over 90 minutes on day 1. Cycles repeat every 14 days in the absence of disease progression or unacceptable toxicity.
Arm II (cetuximab, placebo, irinotecan)
ACTIVE COMPARATORPatients receive cetuximab IV over 90-120 minutes, placebo IV over 30-90 minutes, and irinotecan IV over 90 minutes on day 1. Cycles repeat every 14 days in the absence of disease progression or unacceptable toxicity.
Interventions
Given IV
Given IV
Given IV
Correlative studies
Given IV
Eligibility Criteria
You may qualify if:
- Metastatic or locally advanced (unresectable) colorectal cancer with histological confirmation of adenocarcinoma
- Measurable disease
- RAS wild-type tumor; Note: evidence of EGFR expression in the tumor is not required
- Previous failure of at least one fluoropyrimidine- and irinotecan-containing chemotherapy regimen for metastatic disease; Note: previous failure is defined as disease progression while receiving treatment or within 6 weeks after the last dose of irinotecan; failure for this assessment is defined as any enlargement of measurable or assessable lesion(s) or the development of any new lesion; a rising tumor marker alone is not sufficient to define failure; patients can have received irinotecan in any previous line of therapy
- Treatment with bevacizumab in at least one prior line of therapy for metastatic disease
- Negative serum or urine pregnancy test done =\< 7 days prior to registration, for women of childbearing potential only
- Eastern Cooperative Oncology Group (ECOG) performance status (PS): 0 or 1
- Total serum bilirubin =\< institutional upper limit of normal (ULN) obtained =\<14 days prior to randomization
- Absolute neutrophil count (ANC) \>= 1500/mm\^3 obtained =\<14 days prior to randomization
- Platelet count \>= 100,000/mm\^3 obtained =\<14 days prior to randomization
- Hemoglobin \>= 9.0 g/dL (hemoglobin may be supported by transfusion) obtained =\<14 days prior to randomization
- Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =\< 2.5 x ULN (=\< 5 x ULN for subjects with liver involvement of their cancer) obtained =\<14 days prior to randomization
- Creatinine within institutional limits of normal OR creatinine clearance \>= 60 mL/min/1.73 m\^2 for patients with creatinine levels above institutional normal obtained =\<14 days prior to randomization
- Urinary protein =\< 1+ obtained =\<14 days prior to randomization
- Patients discovered to have \>= 2+ proteinuria must have a spot urine protein:creatinine ratio (UPCR) \< 1.0
- +10 more criteria
You may not qualify if:
- Presence of a RAS mutation in exons 2, 3, or 4 of KRAS or NRAS (patients with mutations in exons 2, 3, or 4 of KRAS and/or NRAS are excluded)
- Prior treatment with cetuximab or panitumumab
- Prior intolerance to irinotecan and/or bevacizumab despite dose reduction
- Known or suspected brain or central nervous system (CNS) metastases, or carcinomatous meningitis
- Active, uncontrolled infection, including hepatitis B, hepatitis C
- Concurrent anti-cancer therapy, including chemotherapy agents, targeted agents, or biological agents not otherwise specified in this protocol
- Anti-cancer therapy =\< 14 days prior to randomization
- Prior radiotherapy to \> 25% of bone marrow; Note: standard rectal cancer chemoradiation will not exclude subject from study protocol
- Radiation therapy =\< 2 weeks prior to randomization
- Any of the following:
- Pregnant women
- Nursing women
- Men or women of childbearing potential who are unwilling to employ adequate contraception
- Co-morbid systemic illnesses or other severe concurrent disease, history of any psychiatric or addictive disorder, or laboratory abnormality, which, in the judgment of the investigator, would make the patient inappropriate for entry into this study or interfere significantly with the proper assessment of safety and toxicity of the prescribed regimens
- Patients known to be human immunodeficiency virus (HIV) positive
- +13 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (13)
Mayo Clinic in Arizona
Scottsdale, Arizona, 85259, United States
Saint Luke's Mountain States Tumor Institute
Boise, Idaho, 83712, United States
Siouxland Regional Cancer Center
Sioux City, Iowa, 51101, United States
Cancer Center of Kansas - Wichita
Wichita, Kansas, 67214, United States
Ochsner Medical Center Jefferson
New Orleans, Louisiana, 70121, United States
Dana-Farber Cancer Institute
Boston, Massachusetts, 02215, United States
Michigan Cancer Research Consortium NCORP
Ann Arbor, Michigan, 48106, United States
Mayo Clinic
Rochester, Minnesota, 55905, United States
Heartland Regional Medical Center
Saint Joseph, Missouri, 64507, United States
Missouri Baptist Medical Center
St Louis, Missouri, 63131, United States
New Hampshire Oncology Hematology PA-Hooksett
Hooksett, New Hampshire, 03106, United States
State University of New York Upstate Medical University
Syracuse, New York, 13210, United States
Saint Vincent Regional Cancer Center CCOP
Green Bay, Wisconsin, 54301, United States
Related Publications (1)
Lipsyc-Sharf M, Ou FS, Yurgelun MB, Rubinson DA, Schrag D, Dakhil SR, Stella PJ, Weckstein DJ, Wender DB, Faggen M, Zemla TJ, Heying EN, Schuetz SR, Noble S, Meyerhardt JA, Bekaii-Saab T, Fuchs CS, Ng K. Cetuximab and Irinotecan With or Without Bevacizumab in Refractory Metastatic Colorectal Cancer: BOND-3, an ACCRU Network Randomized Clinical Trial. Oncologist. 2022 Apr 5;27(4):292-298. doi: 10.1093/oncolo/oyab025.
PMID: 35380713DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Kimmie Ng, M.D., M.P.H.
- Organization
- Dana-Farber Cancer Institute
Study Officials
- PRINCIPAL INVESTIGATOR
Kimmie Ng
Academic and Community Cancer Research United
Publication Agreements
- PI is Sponsor Employee
- No
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- RANDOMIZED
- Masking
- DOUBLE
- Who Masked
- PARTICIPANT, INVESTIGATOR
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
November 13, 2014
First Posted
November 17, 2014
Study Start
December 12, 2014
Primary Completion
March 20, 2019
Study Completion
September 27, 2019
Last Updated
January 31, 2022
Results First Posted
February 28, 2020
Record last verified: 2019-08