Bevacizumab + Triplet Treatment for Untreated With Chemotherapy Metastatic Colorectal Cancer (BeTRI)

Translational Research Center for Medical Innovation, Kobe, Hyogo, Japan

Status and phase: Completed; Phase 2

Conditions: Metastatic Colorectal Cancer

Treatments: Drug: Levofolinate calcium (l-LV); Drug: Oxaliplatin (L-OHP); Drug: Bevacizumab (Bmab); Drug: Continuous intravenous infusion of fluorouracil (CIV 5-FU); Drug: Irinotecan hydrochloride hydrate (CPT-11)

Study type: Interventional

Funder types: Other

Identifiers

NCT02497157

UMIN000017102 (Other Identifier)

TRICC1414

Details and patient eligibility

About

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.

Enrollment: 45 estimated patients

Sex: All

Ages: 20 to 70 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

---

45 participants in 1 patient group

Treatment Arm

Experimental group

Description:

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:

Drug: Continuous intravenous infusion of fluorouracil (CIV 5-FU)

Drug: Levofolinate calcium (l-LV)

Drug: Irinotecan hydrochloride hydrate (CPT-11)

Drug: Oxaliplatin (L-OHP)

Drug: Bevacizumab (Bmab)