Phase II study of FOLFIRI+Ramucirumab with recurrent colorectal cancer refractory to adjuvant chemotherapy (RAINCLOUD). RAINCLOUD-TR.

JRCT ID: jRCTs051180238

Registered date:30/03/2019

Basic Information

• Recruitment status: Complete
• Health condition(s) or Problem(s) studied: recurrent colorectal cancer refractory to adjuvant chemotherapy with oxaliplatin / fluoropyrimidine
• Date of first enrollment: 21/09/2017
• Target sample size: 48
• Study type: Interventional

Intervention(s)

FOLFIRI+Ramucirumab
(5-FU(bolus): 400mg/m2 on day1,
5-FU(ci): 2,400mg/m2 on day1-3 (46hr), l-LV: 200mg/m2 on day1,
CPT-11: 180mg/m2 on day1, Ramucirumab: 8mg/kg on day1) *Allow dose level -1 (150mg/m2)

RAINCLOUD-TR
Collecting blood 12mL at the time of before RAINCLOUD protocol treatment, and PD.

Outcome(s)

• Primary Outcome: Progression free survival
• Secondary Outcome: Overall Survival , Time to treatment failure , Response Rate , Disease Control Rate , Adverse Event

Key inclusion & exclusion criteria

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

Include criteria

1) The patient has histologically or cytologically confirmed colorectal cancer (is not included appendiceal cancer)
2) The patient has confirmed recurrent colorectal cancer
3) The patients who has a history of receiving oxaliplatin and fluoropyrimidine as adjuvant chemotherapy and corresponded to the one of the following criterion,
a) experienced radiographic recurrence during chemotherapy
b) experienced radiographic recurrence within 12 months after discontinuation of chemotherapy due to the adverse events
c) experienced radiographic recurrence within 12 months after the completion of scheduled chemotherapy
d) doctor judged the patients were intolerant to oxaliplatin (peripheral neuropathy, allergy and others, necessary to write the event). irrespective of the duration after neo-adjuvant or adjuvant chemotherapy)
*Neo-adjuvant or adjuvant chemotherapy is counted as 1 regimen.
(1) Combination of anti-VEGF antibody is not allowed.
(2) Combination of anti-EGFR antibody is allowed for RAS wild type colorectal cancer.
4)The patient has measureable disease based on the Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST v 1.1)
5) The patient who is expected to survive more than 3 months after the initiation of administration.
6) The patient has resolution to Grade=<1, per the National Cancer Institute Common Terminology Criteria for Adverse Events, Version 4.03 (NCI-CTCAE v. 4.03), of all clinically significant toxic effects of prior chemotherapy, surgery, radiotherapy, or hormonal therapy, with the exception of peripheral neuropathy, which must have resolved to Grade=<2 and except where otherwise noted in the eligibility criteria.
7) The patient has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
8) The patient has adequate hematologic function as defined by absolute neutrophil count (ANC) >= 1.5 x 103/microL (1.5 x 109/L), hemoglobin >= 9 g/dL, and platelets >= 100 x 103/microL (100 x 109/L).
9) The patient has adequate coagulation function.
a) International Normalized Ratio (INR) =< 1.5 if not receiving anticoagulation therapy.
b) Patients on full-dose anticoagulation must be on a stable dose (INR =< 3.0, minimum duration 14 days) of oral or parenteral (i.e., LMWH; low molecular weight heparin) anticoagulant therapy and if receiving anticoagulation therapy. Prior to the study Patients receiving warfarin must be switched to low molecular weight heparin. For heparin and LMWH there should be no active bleeding (that is, no bleeding within 14 days prior to first dose of protocol therapy) or pathological condition present that carries a high risk of bleeding (for example, tumor involving major vessels or known varices).
10) They are clinically stable, asymptomatic, and adequately treated with anticoagulation in the opinion of the investigator.
11) The patient has adequate hepatic function as defined by a total bilirubin =< 1.5mg/dl and aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 100IU/L (=< 150 IU/L in the case of liver metastases).
12) The patient has adequate renal function as defined by creatinine clearance > 50 mL/min measured either by a 24-hour urine collection or calculated by an equation that is endorsed by local institutional guidelines (for example, Cockcroft-Gault formula).
13) The patient's urinary protein is less than 1+ on dipstick or routine urinalysis.
14) The patient has had disease notification and is able to provide signed informed consent.
15) The patient is >= 20 years of age.
Eligible patients of reproductive potential (both sexes) must agree to use adequate contraception methods (hormonal or barrier methods) during the study period and at least 12 weeks after the last dose of study treatment or longer if required per local regulations.

RAINCLOUD-TR
1) Approved to supply the samples for this study by Institutional Review Board
2) Written informed consent

Exclude criteria

1) The patient has simultaneous or metachronous (disease free duration is within 5 years) double cancers except intramucosal tumor or carcinoma in situ curable with local therapy.
2) The patient has a history of uncontrolled hereditary or acquired bleeding or thrombotic disorders.
3) The patient has an uncontrolled intercurrent illness, including, but not limited to uncontrolled hypertension, symptomatic congestive heart failure (CHF), unstable angina pectoris, symptomatic or poorly controlled cardiac arrhythmia, inflammatory bowel disease, cirrhosis (Child B or worse), psychiatric illness/social situations, or any other serious uncontrolled medical disorders in the opinion of the investigator.
4) The patient has experienced any arterial thrombotic or arterial thromboembolic events, including but not limited to myocardial infarction, transient ischemic attack, or cerebrovascular accident, within 12 months prior to randomization.
5) The patient is receiving chronic antiplatelet therapy, including aspirin, nonsteroidal anti-inflammatory drugs (NSAIDs, including ibuprofen, naproxen, and others), dipyridamole or clopidogrel, or similar agents. Once-daily aspirin use (maximum dose 325 mg/day) is permitted.
6) The patient has known (currently or in the past) leptomeningeal disease or brain metastases or uncontrolled spinal cord compression.
7) The patient has an ongoing or active infection requiring parenteral antibiotic, antifungal, or antiviral therapy.
8) The patient who either of HIV-1 antibody, HIV-2 antibody or HBs antigen is positive.
9) The patient who is HBs antibody or HBc antibody positive and HBV-DNA positive.
10) The patient has received a prior autologous or allogeneic organ or transplantation.
11) The patient has undergone major surgery within 28 days prior to randomization or subcutaneous venous access device placement within 7 days prior to randomization.
12) The patient has had a serious nonhealing wound, ulcer, or bone fracture within 28 days prior to randomization.
13) The patient has an elective or planned major surgery to be performed during the course of the trial.
14) The patient has an acute or subacute bowel obstruction or history of chronic diarrhea which is considered clinically significant in the opinion of the investigator.
15) The patient has experienced a Grade 3 or higher bleeding event within 3 months prior to randomization.
16) The patient has either peptic ulcer disease associated with a bleeding event, or known active diverticulitis.
17) The patient has a known history or clinical evidence of Gilbert's Syndrome, or is known to have any of the following genotypes: UGT1A1*6/*6, UGT1A1*6/*28, UGT1A1*28/*28
18) The patient who desires to have children.
19) The patient whose participation is in the trial is inappropriate by the doctor.

RAINCLOUD-TR
1) Patients who are regarded as inadequate for study enrollment by investigators
2) Patients who refuse to supply the samples

Related Information

• Primary Sponsor: Sugimoto Naotoshi
• Source(s) of Monetary Support: Eli Lilly Japan K.K.
• Secondary ID(s): UMIN000028677,UMIN000028678