Phase II Trial of FOLFOXIRI + Bevacizumab in Patients With Untreated Metastatic Colorectal Cancer
Overview
- Phase
- Phase 2
- Intervention
- Oxaliplatin (L-OHP)
- Conditions
- Metastatic Colorectal Cancer
- Sponsor
- Translational Research Center for Medical Innovation, Kobe, Hyogo, Japan
- Enrollment
- 45
- Locations
- 7
- Primary Endpoint
- Response rate (RR) by response evaluation criteria in solid tumors (RECIST v1.1)
- Status
- Completed
- Last Updated
- 5 years ago
Overview
Brief Summary
The purpose of this study is to evaluate the efficacy and safety of fluorouracil (5-FU), levofolinate calcium (l-LV), oxaliplatin (L-OHP) and irinotecan hydrochloride hydrate (CPT-11) (FOLFOXIRI) plus bevacizumab in untreated metastatic colorectal cancer patients who harbor Uridine diphosphate (UDP)-glucuronosyl transferase 1A1 (UGT1A1) *1/*1, *1/*6 or *1/*28.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Histologically confirmed adenocarcinoma of the colon or rectum.
- •Unresectable or recurrent colorectal cancer patient.
- •One or more measurable lesion in RECIST ver.1.1 criteria.
- •No prior chemotherapy, immunotherapy, and radiotherapy.
- •Life expectancy at least 3 months.
- •Patients who harbor UGT1A1\*1/\*1, \*1/\*6 or \*1/\*
- •The Eastern Cooperative Oncology Group (ECOG) performance status of =\<
- •Vital organ functions (listed below) are preserved within 14 days prior to entry.
- •White blood cell count (WBC): \>= 3,000 per cubic millimeter Neu: \>= 1,500 per cubic millimeter Platelet count (PLT): \>= 100,000 per cubic millimeter Aspartate aminotransferase (AST/GOT) and alanine aminotransferase (ALT/GPT): \<= 100 IU/L, \<= 150 IU/L in cases with liver metastasis T-bil: \<= 1.5 mg/dL Serum creatinine: \<= 1.50 mg/dL Proteinuria: \<= 1+ Prothrombin time-international normalized ratio (PT-INR): \< 1.5
- •Written informed consent.
Exclusion Criteria
- •Vermiform appendix cancer and anal canal cancer.
- •Administration of blood products/ granulocyte-colony stimulating factor (G-CSF), and blood transfusion within 14 days prior to enrollment.
- •Synchronous multiple malignancy or metachronous multiple malignancy less than 5 years disease free interval.
- •Hepatitis B virus antigen (HBs-Ag)(+), or hepatitis C virus antibody (HCV-Ab)(+).
- •History of severe allergy.
- •Sensory alteration or paresthesia interfering with function.
- •Prior radiotherapy for ilium and abdomen.
- •Infectious disease.
- •Uncontrolled diarrhea.
- •Ileus or bowel obstruction.
Arms & Interventions
Treatment Arm
Patients receive FOLFOXIRI plus bevacizumab \[oxaliplatin (L-OHP): 85 mg/sq.m., irinotecan hydrochloride hydrate (CPT-11): 165 mg/sq.m., continuous intravenous infusion of fluorouracil (CIV 5-FU): 3,200 mg/sq.m., Levofolinate calcium (l-LV): 200 mg/sq.m., bevacizumab: 5 mg/kg\]. The treatment will be repeated every 2 weeks, for up to 12 cycles, unless the disease progression, unacceptable toxicity, tumor resection or consent withdrawal.
Intervention: Oxaliplatin (L-OHP)
Treatment Arm
Patients receive FOLFOXIRI plus bevacizumab \[oxaliplatin (L-OHP): 85 mg/sq.m., irinotecan hydrochloride hydrate (CPT-11): 165 mg/sq.m., continuous intravenous infusion of fluorouracil (CIV 5-FU): 3,200 mg/sq.m., Levofolinate calcium (l-LV): 200 mg/sq.m., bevacizumab: 5 mg/kg\]. The treatment will be repeated every 2 weeks, for up to 12 cycles, unless the disease progression, unacceptable toxicity, tumor resection or consent withdrawal.
Intervention: Irinotecan hydrochloride hydrate (CPT-11)
Treatment Arm
Patients receive FOLFOXIRI plus bevacizumab \[oxaliplatin (L-OHP): 85 mg/sq.m., irinotecan hydrochloride hydrate (CPT-11): 165 mg/sq.m., continuous intravenous infusion of fluorouracil (CIV 5-FU): 3,200 mg/sq.m., Levofolinate calcium (l-LV): 200 mg/sq.m., bevacizumab: 5 mg/kg\]. The treatment will be repeated every 2 weeks, for up to 12 cycles, unless the disease progression, unacceptable toxicity, tumor resection or consent withdrawal.
Intervention: Continuous intravenous infusion of fluorouracil (CIV 5-FU)
Treatment Arm
Patients receive FOLFOXIRI plus bevacizumab \[oxaliplatin (L-OHP): 85 mg/sq.m., irinotecan hydrochloride hydrate (CPT-11): 165 mg/sq.m., continuous intravenous infusion of fluorouracil (CIV 5-FU): 3,200 mg/sq.m., Levofolinate calcium (l-LV): 200 mg/sq.m., bevacizumab: 5 mg/kg\]. The treatment will be repeated every 2 weeks, for up to 12 cycles, unless the disease progression, unacceptable toxicity, tumor resection or consent withdrawal.
Intervention: Levofolinate calcium (l-LV)
Treatment Arm
Patients receive FOLFOXIRI plus bevacizumab \[oxaliplatin (L-OHP): 85 mg/sq.m., irinotecan hydrochloride hydrate (CPT-11): 165 mg/sq.m., continuous intravenous infusion of fluorouracil (CIV 5-FU): 3,200 mg/sq.m., Levofolinate calcium (l-LV): 200 mg/sq.m., bevacizumab: 5 mg/kg\]. The treatment will be repeated every 2 weeks, for up to 12 cycles, unless the disease progression, unacceptable toxicity, tumor resection or consent withdrawal.
Intervention: Bevacizumab (Bmab)
Outcomes
Primary Outcomes
Response rate (RR) by response evaluation criteria in solid tumors (RECIST v1.1)
Time Frame: Up to 18 months
RR will be calculated as the ratio of the number of eligible patients who experienced a confirmed Complete response(CR) or Partial response(PR) by RECIST v1.1.
Secondary Outcomes
- Overall survival (OS)(Up to 3 years)
- Incidence of adverse events(Up to 3 years)
- Progression-free survival (PFS)(Up to 3 years)
- Time to treatment failure (TTF)(Up to 18 months)
- R0 resection rate(Up to 18 months)
- Relative dose intensity (RDI)(Up to 18 months)