JCOG2004: Randomized Phase II Study of Bevacizumab plus FOLFIRI versus Ramucirumab plus FOLFIRI versus Aflibercept plus FOLFIRI for Metastatic Colorectal Cancer after failure of First-line chemotherapy with Fluoropyrimidine and Oxaliplatin to Explore Predictive Biomarker

JRCT ID: jRCTs031220058

Registered date:11/05/2022

Basic Information

• Recruitment status: Recruiting
• Health condition(s) or Problem(s) studied: Metastatic colorectal cancer
• Date of first enrollment: 15/06/2022
• Target sample size: 285
• Study type: Interventional

Intervention(s)

Arm A: Bevacizumab+FOLFIRI
(1) BEV 5 mg/kg iv (over 10 minutes) day 1
(2) l-LV 200 mg/m2 iv (2hr) day 1
(3) IRI 150 mg/m2 iv (90min) day 1
(4) 5-FU 400 mg/m2 bolus day 1
(5) 5-FU 2,400 mg/m2/46h continuous iv day 1-3

Arm B: Ramucirumab+FOLFIRI
(1) RAM 8 mg/kg iv (1hr) day 1
(2) l-LV 200 mg/m2 iv (2hr) day 1
(3) IRI 150 mg/m2 iv (90min) day 1
(4) 5-FU 400 mg/m2 bolus day 1
(5) 5-FU 2,400 mg/m2/46h continuous iv day 1-3

Arm C: Aflibercept+FOLFIRI
(1) AFL 4 mg/kg iv (1hr) day 1
(2) l-LV 200 mg/m2 iv (2hr) day 1
(3) IRI 150 mg/m2 iv (90min) day 1
(4) 5-FU 400 mg/m2 bolus day 1
(5) 5-FU 2,400 mg/m2/46h continuous iv day 1-3

Outcome(s)

• Primary Outcome: Progression-free survival
• Secondary Outcome: Overall survival, Response rate, Adverse events, Serious adverse events

Key inclusion & exclusion criteria

• Age minimum: >= 20age old
• Age maximum: Not applicable
• Gender: Both

Include criteria

1) Histologically proven colorectal adenocarcinoma.
2) Unresectable or reccurent colorectal cancer diagnosed by imaging.
3) The main tumor location is cecum (C), ascending colon (A), transverse colon (T), descending colon (D), sigmoid colon (S), rectal sigmoid (RS),upper rectum (Ra), or lower rectum (Rb).
4) RAS mutation status has been confirmed on RAS mutation analysis.
5) BRAF (V600E) wild.
6) Microsatellite stable and/or Proficient DNA mismatch repair
7) Aged 20 years and older at the time of enrollment.
8) Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2.
9) Having measurable lesion
10) No history of prior irinotecan or ramucirumab or aflivercept.
11) Refractory or intolerance to first-line treatment contained fluoropyrimidine and oxaliplatin
12) No severe stenosis by primary tumor
13) No bowel stenosis due to peritoneal dissemination.
14) No massive ascites or pleural effusion at the time of enrollment.
15) No history of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 6 months prior to registration.
16) No CNS involvement including brain metastasis
17) Main organ functions maintained on examinations performed within 14 days before enrollment
18) Written informed consent to blood sampling for analysis of biomarker
19) Written informed consent to participate in the study

Exclude criteria

1) Synchronous or metachronous ( within 5 years ) malignancies except carcinoma in situ or intramucosal tumor curatively treated with local therapy.
2) Active infection requiring systemic therapy.
3) Fever of 38 degrees Celsius or higher.
4) Pregnant or lactating women, women of childbearing potential, or women within 28 days after delivery.
5) Psychiatric disease.
6) Patients requiring systemic steroids medication.
7) Uncontrollable diabetes mellitus
8) Inadequately controlled hypertension, defined as systolic >= 150 and/or diastolic >= 100 mmHg on anti-hypertensive medications.
9) Inadequately controlled hypertension, defined as systolic >= 150 and/or diastolic >= 100 mmHg on anti-hypertensive medications.
10) Uncontrollable levofolinate, dilated cardiomyopathy, or hypertrophic cardiomyopathy
11) Severe diarrhea
12) Interstitial pneumonia, pulmonary fibrosis, or severe emphysema.
13) History of unstable angina, myocardial infarction, pulmonary embolism, deep vein thrombosis, cerebral hemorrhage, cerebral infarction, transient ischemic attack (TIA), cerebrovascular disturbance, or arterial thromboembolism.
14) Known hypersensitivity to any of the component of Fluorouracil, levofolinate, or bevacizumab.
15) Receiving Atazanavir Sulfate contraindication for irinotecan

Related Information

• Primary Sponsor: HIRONAKA Shuichi
• Source(s) of Monetary Support: National Cancer Center Japan,G&G SCIENCE CO., LTD.