Bevacizumab + Triplet Treatment for Untreated With Chemotherapy Metastatic Colorectal Cancer
- Conditions
- Metastatic Colorectal Cancer
- Interventions
- Drug: Continuous intravenous infusion of fluorouracil (CIV 5-FU)
- Registration Number
- NCT02497157
- Lead Sponsor
- Translational Research Center for Medical Innovation, Kobe, Hyogo, Japan
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 45
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Histologically confirmed adenocarcinoma of the colon or rectum.
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Unresectable or recurrent colorectal cancer patient.
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One or more measurable lesion in RECIST ver.1.1 criteria.
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No prior chemotherapy, immunotherapy, and radiotherapy.
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Life expectancy at least 3 months.
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Patients who harbor UGT1A1*1/*1, *1/*6 or *1/*28.
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The Eastern Cooperative Oncology Group (ECOG) performance status of =<1.
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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
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Written informed consent.
- 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.
- Interstitial lung disease or pulmonary fibrosis.
- Malignant coelomic fluid required drainage.
- Administration of atazanavir sulfate.
- Heart disease to be clinically problem.
- Major surgical procedure or intestinal resection within 28 days prior to enrollment or colostomy within 14 days prior to enrollment.
- Known brain metastasis or strongly suspected of brain metastasis.
- History of a thromboembolic disease.
- Receiving anti-platelet drugs.
- Poorly controlled gastrointestinal ulcer.
- History of intestinal perforation within the past 12 months.
- Poorly controlled hypertension.
- Poorly controlled diabetes mellitus.
- Severe mental disorders.
- Women who are pregnant or nursing, men and women who wish to conceive a child or with no intention to contraception.
- Any other cases who are regarded as inadequate for study enrollment by investigators.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Treatment Arm Irinotecan hydrochloride hydrate (CPT-11) 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. Treatment Arm Oxaliplatin (L-OHP) 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. Treatment Arm Levofolinate calcium (l-LV) 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. Treatment Arm Continuous intravenous infusion of fluorouracil (CIV 5-FU) 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. Treatment Arm Bevacizumab (Bmab) 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.
- Primary Outcome Measures
Name Time Method Response rate (RR) by response evaluation criteria in solid tumors (RECIST v1.1) 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 Outcome Measures
Name Time Method Overall survival (OS) Up to 3 years OS is defined as the time from date of starting treatment until date of death from any cause.
Incidence of adverse events Up to 3 years Progression-free survival (PFS) Up to 3 years PFS is defined as the time from date of starting treatment until date of the first documented progression or death from any cause, whichever comes first.
Time to treatment failure (TTF) Up to 18 months TTF is defined as the time from date of starting treatment until date of treatment discontinuation, the first documented progression or death from any cause, whichever comes first.
R0 resection rate Up to 18 months R0 resection rate will be calculated as the ratio of the number of eligible patients who experienced a complete (R0) resection.
Relative dose intensity (RDI) Up to 18 months RDI will be calculated as the ratio of actual delivered dose intensity in comparison with planned dose intensity. Dose intensity (DI) is defined as the amount of drug delivered per unit time, expressed in mg/m2/week.
Trial Locations
- Locations (7)
Matsuyama Red Cross Hospital
🇯🇵Matsuyama-city, Ehime-prefecture, Japan
Tokushima Red Cross Hospital
🇯🇵Komatsushima-city, Tokushima-prefecture, Japan
Okayama Saiseikai General Hospital
🇯🇵Okayama-city, Okayama-prefecture, Japan
Kagawa University Hospital
🇯🇵Kita-gun, Miki-cho, Kagawa-prefecture, Japan
Kawasaki Medical School Hospital
🇯🇵Kurashiki-city, Okayama-prefecture, Japan
Okayama University Hospital
🇯🇵Okayama-city, Okayama-prefecture, Japan
Okayama Rosai Hospital
🇯🇵Okayama-city, Okayama-prefecture, Japan