Brief Summary
The purpose of this study is to compare how long the participants are disease-free (progression-free survival) when treated with amivantamab and chemotherapy with 5-fluorouracil, leucovorin calcium (folinic acid) or levoleucovorin, oxaliplatin (mFOLFOX6) or 5-fluorouracil, leucovorin calcium (folinic acid) or levoleucovorin, and irinotecan hydrochloride (FOLFIRI) versus cetuximab and mFOLFOX6 or FOLFIRI in adult participants with Kirsten rat sarcoma viral oncogene homolog (KRAS)/ Neuroblastoma RAS viral oncogene homolog (NRAS) and v-Raf murine sarcoma viral oncogene homolog B1 (BRAF) wild type (WT) unresectable or metastatic left-sided colorectal cancer.
Brief Title
A Study of Amivantamab and mFOLFOX6 or FOLFIRI Versus Cetuximab and mFOLFOX6 or FOLFIRI as First-line Treatment in Participants With KRAS/NRAS and BRAF Wild-type Unresectable or Metastatic Left-sided Colorectal Cancer
Categories
Central Contacts
Central Contact Role
Contact
Central Contact Phone
844-434-4210
Central Contact Email
Participate-In-This-Study1@its.jnj.com
Completion Date
Completion Date Type
Estimated
Conditions
Colorectal Neoplasms
Eligibility Criteria
Inclusion Criteria:
* Have histologically or cytologically confirmed adenocarcinoma of the left-sided colorectal cancer. Participants must have unresectable or metastatic disease
* Be diagnosed to have Kirsten rat sarcoma viral oncogene (KRAS), neuroblastoma RAS viral oncogene homolog (NRAS), and v-raf murine sarcoma viral oncogene homolog B (BRAF) wild-type (WT) tumor as determined by local testing
* Must agree to the submission of fresh tumor tissue
* Have measurable disease according to RECIST v1.1
* Have an eastern cooperative oncology group (ECOG) performance status (PS) of 0 or 1
Exclusion Criteria:
* Has medical history of (noninfectious) interstitial lung disease (ILD) /pneumonitis/pulmonary fibrosis or has current ILD/pneumonitis/pulmonary fibrosis, or where suspected ILD/pneumonitis/pulmonary fibrosis cannot be ruled out by imaging at screening
* Has known allergies, hypersensitivity, or intolerance to excipients of any of the following: (a) amivantamab or cetuximab, (b) any component of mFOLFOX6 and, (c) any component of FOLFIRI
* Has a prior or concurrent second malignancy other than the disease under study or one whose natural history or treatment is unlikely to interfere with any study endpoints of safety or the efficacy of the study treatment(s)
* Participant with known mismatch repair deficiency (dMMR)/ high microsatellite instability (MSI-H) status and human epidermal growth factor receptor 2 (HER2)-positive/amplified tumor
* Has prior exposure to any agents that target epidermal growth factor receptor (EGFR) or mesenchymal epithelial transition (MET)
* Have histologically or cytologically confirmed adenocarcinoma of the left-sided colorectal cancer. Participants must have unresectable or metastatic disease
* Be diagnosed to have Kirsten rat sarcoma viral oncogene (KRAS), neuroblastoma RAS viral oncogene homolog (NRAS), and v-raf murine sarcoma viral oncogene homolog B (BRAF) wild-type (WT) tumor as determined by local testing
* Must agree to the submission of fresh tumor tissue
* Have measurable disease according to RECIST v1.1
* Have an eastern cooperative oncology group (ECOG) performance status (PS) of 0 or 1
Exclusion Criteria:
* Has medical history of (noninfectious) interstitial lung disease (ILD) /pneumonitis/pulmonary fibrosis or has current ILD/pneumonitis/pulmonary fibrosis, or where suspected ILD/pneumonitis/pulmonary fibrosis cannot be ruled out by imaging at screening
* Has known allergies, hypersensitivity, or intolerance to excipients of any of the following: (a) amivantamab or cetuximab, (b) any component of mFOLFOX6 and, (c) any component of FOLFIRI
* Has a prior or concurrent second malignancy other than the disease under study or one whose natural history or treatment is unlikely to interfere with any study endpoints of safety or the efficacy of the study treatment(s)
* Participant with known mismatch repair deficiency (dMMR)/ high microsatellite instability (MSI-H) status and human epidermal growth factor receptor 2 (HER2)-positive/amplified tumor
* Has prior exposure to any agents that target epidermal growth factor receptor (EGFR) or mesenchymal epithelial transition (MET)
Inclusion Criteria
Inclusion Criteria:
* Have histologically or cytologically confirmed adenocarcinoma of the left-sided colorectal cancer. Participants must have unresectable or metastatic disease
* Be diagnosed to have Kirsten rat sarcoma viral oncogene (KRAS), neuroblastoma RAS viral oncogene homolog (NRAS), and v-raf murine sarcoma viral oncogene homolog B (BRAF) wild-type (WT) tumor as determined by local testing
* Must agree to the submission of fresh tumor tissue
* Have measurable disease according to RECIST v1.1
* Have an eastern cooperative oncology group (ECOG) performance status (PS) of 0 or 1
* Have histologically or cytologically confirmed adenocarcinoma of the left-sided colorectal cancer. Participants must have unresectable or metastatic disease
* Be diagnosed to have Kirsten rat sarcoma viral oncogene (KRAS), neuroblastoma RAS viral oncogene homolog (NRAS), and v-raf murine sarcoma viral oncogene homolog B (BRAF) wild-type (WT) tumor as determined by local testing
* Must agree to the submission of fresh tumor tissue
* Have measurable disease according to RECIST v1.1
* Have an eastern cooperative oncology group (ECOG) performance status (PS) of 0 or 1
Gender
All
Gender Based
false
Healthy Volunteers
No
Last Update Post Date
Last Update Post Date Type
Actual
Last Update Submit Date
Minimum Age
18 Years
NCT Id
NCT06662786
Org Class
Industry
Org Full Name
Janssen Research & Development, LLC
Org Study Id
61186372COR3001
Overall Status
Recruiting
Phases
Phase 3
Primary Completion Date
Primary Completion Date Type
Estimated
Official Title
A Randomized, Open-label Phase 3 Study of Amivantamab and mFOLFOX6 or FOLFIRI Versus Cetuximab and mFOLFOX6 or FOLFIRI as First-line Treatment in Participants With KRAS/NRAS and BRAF Wild-type Unresectable or Metastatic Left-sided Colorectal Cancer
Primary Outcomes
Outcome Description
PFS is defined as the time from randomization until the date of objective disease progression or death (due to any cause), whichever comes first, as assessed by BICR using response evaluation criteria in solid tumors (RECIST) version (v) 1.1. Participants who have not progressed or have not died at the time of analysis will be censored at their last evaluable RECIST v1.1 assessment date.
Outcome Measure
Progression-Free Survival (PFS) as Assessed by Blinded Independent Central Review (BICR)
Outcome Time Frame
Up to 4 years and 2 months
Secondary Ids
Secondary Id
61186372COR3001
Secondary Id
2024-513852-13-00
Secondary Outcomes
Outcome Description
OS is defined as the time from the date of randomization to the date of participant's death due to any cause. Any participant not known to have died at the time of analysis will be censored based on the last recorded date on which the participant was known to be alive.
Outcome Time Frame
Up to 7 Years 3 Months
Outcome Measure
Overall Survival (OS)
Outcome Description
ORR is defined as the percentage of randomized participants achieving complete response (CR) or partial response (PR), as determined by BICR using RECIST v1.1 criteria.
Outcome Time Frame
Up to 7 Years 3 Months
Outcome Measure
Objective Response Rate (ORR) as Assessed by BICR
Outcome Description
PFS is defined as the time from randomization until the date of objective disease progression or death (due to any cause), whichever comes first, as assessed by the investigator.
Outcome Time Frame
Up to 7 Years 3 Months
Outcome Measure
Progression Free Survival (PFS) as Assessed by Investigator
Outcome Description
ORR is defined as the percentage of randomized participants achieving complete CR or PR, as assessed by the investigator.
Outcome Time Frame
Up to 7 Years 3 Months
Outcome Measure
Objective Response Rate (ORR) as Assessed by Investigator
Outcome Description
DOR is defined as time from the date of first documented response (CR or PR) until the date of documented progression or death, whichever comes first, for participants who have PR or CR, as assessed by BICR using RECIST v1.1 criteria.
Outcome Time Frame
Up to 7 Years 3 Months
Outcome Measure
Duration of Response (DOR) as Assessed by BICR
Outcome Description
DOR is defined as time from the date of first documented response (CR or PR) until the date of documented progression or death, whichever comes first, for participants who have PR or CR, as assessed by the investigator.
Outcome Time Frame
Up to 7 Years 3 Months
Outcome Measure
Duration of Response (DOR) as Assessed Investigator
Outcome Description
PFS2 is defined as the time from randomization until the date of second objective disease progression, after initiation of subsequent anticancer therapy, based on investigator assessment (after that used for PFS) or death, whichever comes first.
Outcome Time Frame
Up to 7 Years 3 Months
Outcome Measure
Progression-free Survival After Subsequent Therapy (PFS2)
Outcome Description
DCR is defined as the percentage of randomized participants achieving CR, PR, or stable disease (with minimum duration of 7 weeks) as assessed by BICR using RECIST v1.1 criteria.
Outcome Time Frame
Up to 7 Years 3 Months
Outcome Measure
Disease Control Rate (DCR) as Assessed by BICR
Outcome Description
DCR is defined as the percentage of randomized participants achieving CR, PR, or stable disease (with minimum duration of 7 weeks) as assessed by the investigator.
Outcome Time Frame
Up to 7 Years 3 Months
Outcome Measure
Disease Control Rate (DCR) as Assessed by Investigator
Outcome Description
Time to treatment failure is defined as time from randomization to discontinuation of therapy for any reason including death, progression, toxicity, or initiation of new anticancer therapy.
Outcome Time Frame
Up to 7 Years 3 Months
Outcome Measure
Time to Treatment Failure
Outcome Description
Curative resection (R0) rate is defined as the percentage of participants (or participants with limited disease at baseline) who underwent curative surgery.
Outcome Time Frame
Up to 7 Years 3 Months
Outcome Measure
Curative Resection (R0) Rate
Outcome Description
An AE can be any unfavorable and unintended sign (including an abnormal finding), symptom, or disease temporally associated with the use of a medicinal (investigational or non-investigational) product, whether or not related to that medicinal (investigational or non-investigational) product. AE severity will be graded according to the national cancer institute common terminology criteria for adverse events (NCI-CTCAE) v5.0. by using the standard grades as follows: Grade 1: Mild; asymptomatic or mild symptoms; Grade 2: Moderate; minimal, local or noninvasive intervention indicated; Grade 3: Severe or medically significant but not immediately life threatening; hospitalization or prolongation of hospitalization indicated; Grade 4: Life-threatening consequences; and Grade 5: Death related to AE.
Outcome Time Frame
Up to 7 Years 3 Months
Outcome Measure
Number of Participants with Adverse Events (AEs) by Severity
Outcome Description
Participants with abnormalities in laboratory values (such as serum chemistry, hematology) will be reported.
Outcome Time Frame
Up to 7 Years 3 Months
Outcome Measure
Number of Participants with Abnormalities in Laboratory Values
Outcome Description
The EORTC QLQ-C30, is a self-administered, 30-item questionnaire measuring the health-related quality of life (HRQoL) of participants with cancer. EORTC QLQ-C30 includes 5 functional scales, 3 symptom scales, a global health status / quality of life scale, and 6 single items. Responses to items 1-28 are rated on a 4-point Likert response scale ranging from 1 "Not at all" to 4 "Very much." Two global health status items are rated on a 7-point numeric rating scale from 1 "Very Poor" to 7 "Excellent." Higher scores indicate greater functioning, better global health status, and more severe symptoms.
Outcome Time Frame
From Baseline up to 7 Years 3 Months
Outcome Measure
Change From Baseline in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) Score
Outcome Description
The EORTC QLQ-C30, is a self-administered, 30-item questionnaire measuring the HRQoL of participants with cancer. EORTC QLQ-C30 includes 5 functional scales, 3 symptom scales, a global health status / quality of life scale, and 6 single items. Responses to items 1-28 are rated on a 4-point Likert response scale ranging from 1 "Not at all" to 4 "Very much." Two global health status items are rated on a 7-point numeric rating scale from 1 "Very Poor" to 7 "Excellent." Higher scores indicate greater functioning, better global health status, and more severe symptom.
Outcome Time Frame
Up to 7 Years 3 Months
Outcome Measure
Time to Worsening in Symptoms and Functioning as Measured by EORTC QLQ-C30
Outcome Description
The EORTC QLQ-CR29, is a self-administered, 29-item questionnaire measuring the HRQoL of participants with colorectal cancer. The QLQ CR29 includes items that evaluate symptoms (gastrointestinal, urinary, pain, and others) and functional areas (sexual, body image, weight, and anxiety) that are associated with colorectal cancer and its treatments. Responses are rated on a 4-point Likert response scale ranging from 1 "Not at all" to 4 "Very much". All scores are linearly converted into a scale from 0 to 100. Higher scores indicate greater functioning and more severe symptoms.
Outcome Time Frame
From Baseline up to 7 Years 3 Months
Outcome Measure
Change from Baseline in European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Colorectal Cancer Module 29 (EORTC-QLQ-C30) Score
Outcome Description
The EORTC QLQ-CR29, is a self-administered, 29-item questionnaire measuring the HRQoL of participants with colorectal cancer. The QLQ CR29 includes items that evaluate symptoms (gastrointestinal, urinary, pain, and others) and functional areas (sexual, body image, weight, and anxiety) that are associated with colorectal cancer and its treatments. Responses are rated on a 4-point Likert response scale ranging from 1 "Not at all" to 4 "Very much". All scores are linearly converted into a scale from 0 to 100. Higher scores indicate greater functioning and more severe symptoms.
Outcome Time Frame
Up to 7 Years 3 Months
Outcome Measure
Time to Worsening in Symptoms and Functioning as Measured by EORTC QLQ-CR29
Outcome Description
The EORTC item 168 is a single item used to measure the overall impact of treatment side effects. Responses are rated on a 4-point Likert response scale ranging from 1 "not at all" to 4 "very much." Higher scores indicate severe side effects.
Outcome Time Frame
Up to 7 Years 3 Months
Outcome Measure
Overall Side Effect Burden as Measured by European Organisation for Research and Treatment of Cancer (EORTC) Item 168 Scale Score
Start Date
Start Date Type
Actual
Status Verified Date
First Post Date
First Post Date Type
Actual
First Submit Date
First Submit QC Date
Std Ages
Adult
Older Adult
Maximum Age Number (converted to Years and rounded down)
999
Minimum Age Number (converted to Years and rounded down)
18
Investigators
Investigator Type
Principal Investigator
Investigator Name
Fernand Bteich
Investigator Email
fbteich@montefiore.org