Colorectal Neoplasms
Conditions
Brief summary
The purpose of this study is to compare how long the participants are disease-free (progression-free survival) and and the length of time until a participant dies (overall survival), when treated with amivantamab and chemotherapy with 5-fluorouracil, leucovorin calcium (folinic acid) or levoleucovorin, and irinotecan hydrochloride (FOLFIRI) versus either cetuximab or bevacizumab and FOLFIRI given to participants with Kirsten rat sarcoma viral oncogene/ neuroblastoma RAS viral oncogene homolog (KRAS/ NRAS) and v-raf murine sarcoma viral oncogene homolog B (BRAF) wild-type recurrent, unresectable or metastatic colorectal cancer who have previously received chemotherapy.
Interventions
BIOLOGICALAmivantamab
Amivantamab will be administered.
BIOLOGICALCetuximab
Cetuximab will be administered.
BIOLOGICALBevacizumab
Bevacizumab will be administered.
DRUG5-fluorouracil
5-fluorouracil will be administered as chemotherapy regimen.
Leucovorin calcium/Levoleucovorin will be administered as chemotherapy regimen.
DRUGIrinotecan
Irinotecan will be administered as chemotherapy regimen.
Sponsors
Janssen Research & Development, LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Have histologically or cytologically confirmed adenocarcinoma of the colon or rectum. Participants must have recurrent, unresectable or metastatic disease * Determined to have kirsten rat sarcoma viral oncogene/neuroblastoma RAS viral oncogene homolog (KRAS/NRAS), G12, G13 and v-raf murine sarcoma viral oncogene homolog B (BRAF) V600X (X represents any single amino acid change from the original amino acid) wild type status by local and/or central next-generation sequencing (NGS) testing * Must agree to the submission of fresh or archival tumor tissue post progression from the most recent therapy, if clinically feasible * Have measurable disease according to response evaluation criteria in solid tumors (RECIST) version (v) 1.1 * Have an eastern cooperative oncology group (ECOG) performance status (PS) of 0 or 1 * Participant must have received 1 line of systemic therapy (fluoropyrimidine-based and oxaliplatin-based) for metastatic colorectal cancer (mCRC), with documented radiographic disease progression on or after this line of therapy. Participants can receive anti-VEGF as prior line of therapy
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: amivantamab, cetuximab or bevacizumab or 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 likely 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 who has not received immunotherapy treatments * Participant with known human epidermal growth factor receptor 2 (HER2)- positive/amplified tumor * Has prior exposure to irinotecan, any agents that target epidermal growth factor receptor (EGFR) or mesenchymal epithelial transition (MET)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression-Free Survival (PFS) as Assessed by Blinded Independent Central Review (BICR) | Up to 2 years 1 month | 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. |
| Overall Survival (OS) | Up to 4 years 4 months | OS is defined as the time from the date of randomization to the date of participant's death due to any cause. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response Rate (ORR) as Assessed by BICR | Up to 4 years 4 months | ORR is defined as the percentage of randomized participants achieving partial response (PR) or complete response (CR), as determined by BICR using RECIST v1.1 criteria. |
| ORR as Assessed by Investigator | Up to 4 years 4 months | ORR is defined as the percentage of randomized participants achieving partial response (PR) or complete response (CR), as determined by investigator using RECIST v1.1 criteria. |
| Progression Free Survival as Assessed by Investigator | Up to 4 years 4 months | 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 investigator. |
| Duration of Response (DoR) as Assessed by BICR | Up to 4 years 4 months | 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. |
| Duration of Response as Assessed by Investigator | Up to 4 years 4 months | 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 investigator. |
| Time to Response (TTR) as Assessed by BICR | Up to 4 years 4 months | TTR is defined as the time from the date of randomization to the date of first documentation of a response (PR or CR) prior to any disease progression or subsequent systemic anti-cancer therapy or curative-intent procedure, for participants who have PR or CR as BOR, as assessed by BICR. |
| TTR as Assessed by Investigator | Up to 4 years 4 months | TTR is defined as the time from the date of randomization to the date of first documentation of a response (PR or CR) prior to any disease progression or subsequent systemic anti-cancer therapy or curative-intent procedure, for participants who have PR or CR as BOR, as assessed by investigator. |
| Progression Free Survival After Subsequent Therapy (PFS2) | Up to 4 years 4 months | PFS2 is defined as the time from randomization until the date of second objective disease progression, after initiation of subsequent systemic anticancer therapy, based on investigator assessment or death, whichever comes first. |
| Disease Control Rate (DCR) as Assessed by BICR | Up to 4 years 4 months | DCR is defined as the percentage of randomized participants achieving CR, PR, or stable disease (with a minimum duration of 7 weeks) as defined by BICR using RECIST v1.1. |
| Disease Control Rate as Assessed by Investigator | Up to 4 years 4 months | DCR is defined as the percentage of randomized participants achieving CR, PR, or stable disease (with a minimum duration of 7 weeks) as assessed by investigator. |
| Time to Treatment Failure | Up to 4 years 4 months | 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. |
| Curative Resection (R0) Rate | Up to 4 years 4 months | Curative resection (R0) rate is defined as the percentage of randomized participants who underwent curative-intent surgery where the residual tumor classification was R0. |
| Number of Participants with Adverse Events (AEs) by Severity | Up to 4 years 4 months | An AE is any untoward medical occurrence in a participant administered a pharmaceutical (investigational or non investigational) product. An AE does not necessarily have a causal relationship with the treatment. Severity of AEs will be graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) v5.0. by using standard grades as follows: Grade 1: Mild; asymptomatic or mild symptoms; Grade 2: Moderate; minimal, local or noninvasive intervention indicated; Grade 3: Severe but not immediately life threatening; hospitalization or prolongation of hospitalization indicated; Grade 4: Life-threatening consequences; and Grade 5: Death related to AE. |
| Number of Participants with Abnormalities in Laboratory Values | Up to 4 years 4 months | Participants with abnormalities in laboratory values (such as serum chemistry, hematology) will be reported. |
| Change From Baseline in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) Score | From baseline up to 4 years 4 months | 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. |
| Time to Worsening in Symptoms and Functioning as Measured by EORTC QLQ-C30 | Up to 4 years 4 months | Time to worsening in symptoms and functioning as measured by EORTC QLQ-C30 score will be reported. 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. |
| Change From Baseline in European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-CR29) Score | From baseline up to 4 years 4 months | 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. |
| Time to Worsening in Symptoms and Functioning as Measured by EORTC QLQ-CR29 Score | Up to 4 years 4 months | Time to worsening in symptoms and functioning as measured by EORTC QLQ-CR29 will be reported. 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. Change from baseline in the EORTC QLQ-CR29 score will be reported. |
| Overall Side Effect Burden as Measured by European Organisation for Research and Treatment of Cancer (EORTC) Item 168 Scale Score | Up to 4 years 4 months | 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 indicates severe symptoms. |
Countries
Australia, Belgium, Brazil, China, France, Germany, Hong Kong, Hungary, India, Israel, Italy, Japan, Malaysia, Mexico, Netherlands, Poland, Puerto Rico, Romania, South Korea, Spain, Sweden, Taiwan, Thailand, Turkey (Türkiye), United Kingdom, United States
Contacts
CONTACTStudy Contact
STUDY_DIRECTORJanssen Research & Development, LLC Clinical Trial
Janssen Research & Development, LLC
Outcome results
None listed