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

JRCT ID: jRCT2031240455

Registered date:05/11/2024

Basic Information

• Recruitment status: Pending
• Health condition(s) or Problem(s) studied: Colorectal Neoplasms
• Date of first enrollment: 16/12/2024
• Target sample size: 1000
• Countries of recruitment: Malaysia,Japan,Sweden,Japan,United Kingdom Of Great Britain,Japan,China,Japan,Belgium,Japan,Brazil,Japan,Spain,Japan,India,Japan,Canada,Japan,Israel,Japan,Germany,Japan,Italy,Japan,United States Of America,Japan,France,Japan,Poland,Japan,Turkiye,Japan,Taiwan Province Of China,Japan,Korea,Japan,Netherlands,Japan,Hungary,Japan
• Study type: Interventional

Intervention(s)

-Arm A Amivantamab:Amivantamab in Combination With Chemotherapy: Participants will receive amivantamab in combination with chemotherapy (mFOLFOX6 [chemotherapy consisting of 5-fluorouracil, leucovorin calcium (folinic acid) or levoleucovorin, and oxaliplatin] or FOLFIRI [chemotherapy consisting of 5-fluorouracil, leucovorin calcium (folinic acid) or levoleucovorin, and irinotecan hydrochloride]) for 28-days treatment cycles and will continue to receive thetreatment until radiographic disease progression or other discontinuation criteria are met.
-Arm B Cetuximab: Cetuximab in Combination With Chemotherapy: Participants will receive cetuximab in combination with chemotherapy (mFOLFOX6 or FOLFIRI) for 28-days treatment cycles and will continue to receive the treatment until radiographic disease progression or other discontinuation criteria are met.

Outcome(s)

• Primary Outcome: Progression-Free Survival (PFS) as Assessed by Blinded Independent Central Review (BICR):Up to 4 years and 2 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 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.

Secondary Outcome

-Overall Survival (OS): Up to 7 Years 3 Months: 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.
-Objective Response Rate (ORR) as Assessed by BICR: Up to 7 Years 3 Months: 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.
-Progression Free Survival (PFS) as Assessed by Investigator: Up to 7 Years 3 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 the investigator.
-Objective Response Rate (ORR) as Assessed by Investigator: Up to 7 Years 3 Months: ORR is defined as the percentage of randomized participants achieving complete CR or PR, as assessed by the investigator.
-Duration of Response (DOR) as Assessed by BICR: Up to 7 Years 3 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 using RECIST v1.1 criteria.
-Duration of Response (DOR) as Assessed Investigator: Up to 7 Years 3 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 the investigator.
-Progression-free Survival After Subsequent Therapy (PFS2): Up to 7 Years 3 Months: 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.
-Disease Control Rate (DCR) as Assessed by BICR: Up to 7 Years 3 Months: 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.
-Disease Control Rate (DCR) as Assessed by Investigator: Up to 7 Years 3 Months: 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.
-Time to Treatment Failure: Up to 7 Years 3 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 7 Years 3 Months: Curative resection (R0) rate is defined as the percentage of participants (or participants with limited disease at baseline) who underwent curative surgery.
-Number of Participants with Adverse Events (AEs) by Severity: Up to 7 Years 3 Months: 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.
-Number of Participants with Abnormalities in Laboratory Values: Up to 7 Years 3 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 7 Years 3 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 7 Years 3 Months: 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.
-Change from Baseline in European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Colorectal Cancer Module 29 (EORTCQLQ-C30) Score: From Baseline up to 7 Years 3 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: Up to 7 Years 3 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.
-Overall Side Effect Burden as Measured by European Organisation for Research and Treatment of Cancer (EORTC) Item 168 Scale Score: Up to 7 Years 3 Months: 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.

Key inclusion & exclusion criteria

• Age minimum: >= 18age old
• Age maximum: Not applicable
• Gender: Both

Include 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

Exclude 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)

Related Information

• Primary Sponsor: Nakama Takahiro
• Secondary ID(s): 2024-513852-13-00,NCT06662786