Metastatic Colorectal Cancer
Conditions
Keywords
bevacizumab, oxaliplatin, irinotecan, hydrochloride hydrate, fluorouracil, levofolinate calcium
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.
Interventions
DRUGOxaliplatin (L-OHP)
DRUGIrinotecan hydrochloride hydrate (CPT-11)
DRUGContinuous intravenous infusion of fluorouracil (CIV 5-FU)
DRUGLevofolinate calcium (l-LV)
DRUGBevacizumab (Bmab)
Sponsors
Hiroshima Prefectural Hospital
National Hospital Organization Shikoku Cancer Center
Translational Research Center for Medical Innovation, Kobe, Hyogo, Japan
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
20 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
1. Histologically confirmed adenocarcinoma of the colon or rectum. 2. Unresectable or recurrent colorectal cancer patient. 3. One or more measurable lesion in RECIST ver.1.1 criteria. 4. No prior chemotherapy, immunotherapy, and radiotherapy. 5. Life expectancy at least 3 months. 6. Patients who harbor UGT1A1\*1/\*1, \*1/\*6 or \*1/\*28. 7. The Eastern Cooperative Oncology Group (ECOG) performance status of =\<1. 8. 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 9. Written informed consent.
Exclusion criteria
1. Vermiform appendix cancer and anal canal cancer. 2. Administration of blood products/ granulocyte-colony stimulating factor (G-CSF), and blood transfusion within 14 days prior to enrollment. 3. Synchronous multiple malignancy or metachronous multiple malignancy less than 5 years disease free interval. 4. Hepatitis B virus antigen (HBs-Ag)(+), or hepatitis C virus antibody (HCV-Ab)(+). 5. History of severe allergy. 6. Sensory alteration or paresthesia interfering with function. 7. Prior radiotherapy for ilium and abdomen. 8. Infectious disease. 9. Uncontrolled diarrhea. 10. Ileus or bowel obstruction. 11. Interstitial lung disease or pulmonary fibrosis. 12. Malignant coelomic fluid required drainage. 13. Administration of atazanavir sulfate. 14. Heart disease to be clinically problem. 15. Major surgical procedure or intestinal resection within 28 days prior to enrollment or colostomy within 14 days prior to enrollment. 16. Known brain metastasis or strongly suspected of brain metastasis. 17. History of a thromboembolic disease. 18. Receiving anti-platelet drugs. 19. Poorly controlled gastrointestinal ulcer. 20. History of intestinal perforation within the past 12 months. 21. Poorly controlled hypertension. 22. Poorly controlled diabetes mellitus. 23. Severe mental disorders. 24. Women who are pregnant or nursing, men and women who wish to conceive a child or with no intention to contraception. 25. Any other cases who are regarded as inadequate for study enrollment by investigators.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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. |
| 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. |
| 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. |
| Incidence of adverse events | Up to 3 years | — |
| 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. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Early tumor shrinkage (ETS) rates in 8 weeks after starting the treatment, evaluated by RECIST v1.1 | Baseline (week 0), week 8 | ETS will be calculated as the ratio of the number of eligible patients who experienced a 20% or more tumor shrinkage at week 8 compared with baseline. |
| Deepness of response (DoR) | Up to 3 years | DoR will be calculated as the median of the maximum tumor shrinkage rates. |
Countries
Japan
Outcome results
None listed