A Multicenter, Clinical Phase II Study of FOLFOXIRI With Bevacizumab As First-line Therapy in Patients With Metastatic Colorectal Cancer
Overview
- Phase
- Phase 2
- Intervention
- Bevacizumab
- Conditions
- Colorectal Neoplasms
- Sponsor
- EPS Corporation
- Enrollment
- 69
- Locations
- 1
- Primary Endpoint
- Progression-free survival (PFS) at 10 months
- Status
- Completed
- Last Updated
- 8 years ago
Overview
Brief Summary
The purpose of this study to assess efficacy and tolerability of combination therapy FOLFOXIRI with Bevacizumab (BV) as a first-line therapy in patients with metastatic colorectal cancer.
Detailed Description
This is a single-arm, multicentre phase II study evaluating the efficacy and safety of Bevacizumab (BV) in combination with oxaliplatin, irinotecan hydrochloride, fluorouracil, and leucovorin calcium regimen ( FOLFOXIRI +BV ; Falcone et al. ASCO2013) as first-line treatment for Japanese metastatic colorectal cancer patients. This study is composed two steps because of collecting safety issue in Japanese patient. As First step (Step 1), It assess on the initial safety information in ten Japanese patients of the end of 2nd cycle. it is evaluated by DMC. In parallel with the confirmation of the initial safety issue, register up to 65 cases in total and Step 1 patient, to evaluate the efficacy and safety (Step2).
Investigators
Eligibility Criteria
Inclusion Criteria
- •Written Informed consent.
- •Histopathologically proven diagnosis of colorectal cancer (adenocarcinoma) excluding vermiform appendix cancer and proctos cancer.
- •Not resectable metastatic colorectal cancer
- •Age at enrollment is \>= 20 and \<= 75 years
- •ECOG PS \< 2 if age \< 70 years, ECOG PS = 0 if age = 71-75 years
- •One or more measurable lesion in RECIST ver.1.1 criteria according to contrast enhanced CT chest / abdomen / pelvis diagnosis.
- •Not previously treated with chemotherapy. ( Previous adjuvant by fluoropyrimidine monotherapy is allowed if more than 24 weeks have elapsed between the end of adjuvant therapy and first relapse.)
- •Vital organ functions (listed below) are preserved within 2 weeks prior to entry. Data recorded nearest to the entry should be referred. Blood transfusion or erythropoiesis stimulating agents less than 2 weeks prior to the tests are not allowed.
- •Neu. \>= 1,500/cubicmillimeter Pt. \>= 100,000/cubicmillimeter Hb. \>= 9.0 g/dL T-bil. \<= upper limit of normal (ULN)\*1.5 AST and ALT,ALP \<= upper limit of normal (ULN)\*2.5 (\<= ULN\*5 in case of liver metastasis) Serum creatinine \<= upper limit of normal (ULN) \*1.5 PT-INR \< 1.5 Proteinuria \<= 2+
- •UGT1A1 genotype tested. Categorized into Wild or single Hetero.
Exclusion Criteria
- •Previously treated with irradiation to bone marrow constituting 20% or more of irradiation field.
- •Untreated brain metastases or spinal cord compression or primary brain tumors.
- •History of CNS disease.\[except for asymptomatic Lacunar stroke\]
- •Requiring chronic systemic corticosteroid treatment.
- •Current or recent ongoing treatment with anticoagulants.
- •Clinically significant cardiovascular disease for example cerebrovascular accidents, myocardial infarction, unstable angina, congestive heart failure, serious cardiac arrhythmia requiring medication.
- •Treatment with any investigational drug within 4 weeks.
- •Patient with Uncontrolled hypertension, Uncontrolled diabetes, Uncontrolled diarrhea, \>=grade 1 peripheral neuropathy, Active peptic ulcer, Non-healing wound, Clinically important diseases.
- •Major surgical procedure within 28 days prior to study treatment start, open biopsy, or significant traumatic injury, or anticipation of the need for major surgical procedure.\[except for implantation of central venous catheter and port system.\]
- •Lack of physical integrity of the upper gastrointestinal tract.
Arms & Interventions
FOLFOXIRI plus bevacizumab
Induction therapy is followed by the maintenance therapy. \[Induction treatment:FOLFOXIRI plus bevacizumab\] Administered for a maximum of 12 cycles. BV: 5mg/kg (d.i.v.) L-OHP: 85 mg/sq.m (d.i.v.) CPT-11:165mg/sq.m (d.i.v.) l-LV:200mg/sq.m (d.i.v.) 5-FU:3,200mg/sq.m (c.i.v.) Administered every 2 weeks. \[Maintenance treatment:5-FU / I-LV plus bevacizumab\] BV:5mg/kg (d.i.v.) l-LV:200mg/sq.m (d.i.v.) 5-FU:3,200mg/sq.m (c.i.v.) Administered every 2 weeks.
Intervention: Bevacizumab
FOLFOXIRI plus bevacizumab
Induction therapy is followed by the maintenance therapy. \[Induction treatment:FOLFOXIRI plus bevacizumab\] Administered for a maximum of 12 cycles. BV: 5mg/kg (d.i.v.) L-OHP: 85 mg/sq.m (d.i.v.) CPT-11:165mg/sq.m (d.i.v.) l-LV:200mg/sq.m (d.i.v.) 5-FU:3,200mg/sq.m (c.i.v.) Administered every 2 weeks. \[Maintenance treatment:5-FU / I-LV plus bevacizumab\] BV:5mg/kg (d.i.v.) l-LV:200mg/sq.m (d.i.v.) 5-FU:3,200mg/sq.m (c.i.v.) Administered every 2 weeks.
Intervention: 5-fluorouracil
FOLFOXIRI plus bevacizumab
Induction therapy is followed by the maintenance therapy. \[Induction treatment:FOLFOXIRI plus bevacizumab\] Administered for a maximum of 12 cycles. BV: 5mg/kg (d.i.v.) L-OHP: 85 mg/sq.m (d.i.v.) CPT-11:165mg/sq.m (d.i.v.) l-LV:200mg/sq.m (d.i.v.) 5-FU:3,200mg/sq.m (c.i.v.) Administered every 2 weeks. \[Maintenance treatment:5-FU / I-LV plus bevacizumab\] BV:5mg/kg (d.i.v.) l-LV:200mg/sq.m (d.i.v.) 5-FU:3,200mg/sq.m (c.i.v.) Administered every 2 weeks.
Intervention: Irinotecan hydrochloride
FOLFOXIRI plus bevacizumab
Induction therapy is followed by the maintenance therapy. \[Induction treatment:FOLFOXIRI plus bevacizumab\] Administered for a maximum of 12 cycles. BV: 5mg/kg (d.i.v.) L-OHP: 85 mg/sq.m (d.i.v.) CPT-11:165mg/sq.m (d.i.v.) l-LV:200mg/sq.m (d.i.v.) 5-FU:3,200mg/sq.m (c.i.v.) Administered every 2 weeks. \[Maintenance treatment:5-FU / I-LV plus bevacizumab\] BV:5mg/kg (d.i.v.) l-LV:200mg/sq.m (d.i.v.) 5-FU:3,200mg/sq.m (c.i.v.) Administered every 2 weeks.
Intervention: Leucovorin calcium
FOLFOXIRI plus bevacizumab
Induction therapy is followed by the maintenance therapy. \[Induction treatment:FOLFOXIRI plus bevacizumab\] Administered for a maximum of 12 cycles. BV: 5mg/kg (d.i.v.) L-OHP: 85 mg/sq.m (d.i.v.) CPT-11:165mg/sq.m (d.i.v.) l-LV:200mg/sq.m (d.i.v.) 5-FU:3,200mg/sq.m (c.i.v.) Administered every 2 weeks. \[Maintenance treatment:5-FU / I-LV plus bevacizumab\] BV:5mg/kg (d.i.v.) l-LV:200mg/sq.m (d.i.v.) 5-FU:3,200mg/sq.m (c.i.v.) Administered every 2 weeks.
Intervention: Oxaliplatin
Outcomes
Primary Outcomes
Progression-free survival (PFS) at 10 months
Time Frame: PFS rate at 10 months from study entry
PFS by investigator-reported measurements according to CT image. PFS was calculated from the day of treatment start to the first observation of progression disease (PD) or death from any cause. PD was defined as Overall Response by RECIST criteria v1.1 according to CT image.
Secondary Outcomes
- Response rate (RR) by central review.(Up to 18 months)
- Response rate (RR) by investigator-reported measurements.(Up to 30 months)
- PFS by central review according to CT image.(Up to 18 months)
- Overall survival (OS)(Up to 30 months)
- Efficacy by RAS status ; RR,PFS,OS(Up to 30 months)
- Incidence of adverse events(Up to 30 months)
- Time to treatment-failure(Up to 30 months)
- Completion rate in Induction treatment(Up to 30 months)
- Relative Dose Intensity(Up to 30 months)
- Treatment duration(Up to 30 months)