Bevacizumab + Triplet Treatment for Untreated With Chemotherapy Metastatic Colorectal Cancer

Metastatic Colorectal Cancer Clinical Trial

— BeTRI  

Official title:

Phase II Trial of FOLFOXIRI + Bevacizumab in Patients With Untreated Metastatic Colorectal Cancer

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02497157
• Other study ID #: TRICC1414
• Secondary ID: UMIN000017102
• Status: Completed
• Phase: Phase 2
• Start date: May 21, 2015
• Est. completion date: June 2019

Study information

• Verified date: June 2020
• Source: Translational Research Center for Medical Innovation, Kobe, Hyogo, Japan
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 45
• Est. completion date: June 2019
• Est. primary completion date: June 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 20 Years to 70 Years

Eligibility

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.

Related Conditions & MeSH terms

• Colorectal Neoplasms
• Metastatic Colorectal Cancer

Intervention

Drug:
• Oxaliplatin (L-OHP)

• Irinotecan hydrochloride hydrate (CPT-11)

• Continuous intravenous infusion of fluorouracil (CIV 5-FU)

• Levofolinate calcium (l-LV)

• Bevacizumab (Bmab)

Locations

Country	Name	City	State
Japan	Kagawa University Hospital	Kita-gun, Miki-cho	Kagawa-prefecture
Japan	Tokushima Red Cross Hospital	Komatsushima-city	Tokushima-prefecture
Japan	Kawasaki Medical School Hospital	Kurashiki-city	Okayama-prefecture
Japan	Matsuyama Red Cross Hospital	Matsuyama-city	Ehime-prefecture
Japan	Okayama Rosai Hospital	Okayama-city	Okayama-prefecture
Japan	Okayama Saiseikai General Hospital	Okayama-city	Okayama-prefecture
Japan	Okayama University Hospital	Okayama-city	Okayama-prefecture

Sponsors (3)

Lead Sponsor	Collaborator
Translational Research Center for Medical Innovation, Kobe, Hyogo, Japan	Hiroshima Prefectural Hospital, National Hospital Organization Shikoku Cancer Center

Country where clinical trial is conducted

Japan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Early tumor shrinkage (ETS) rates in 8 weeks after starting the treatment, evaluated by RECIST v1.1	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.	Baseline (week 0), week 8
Other	Deepness of response (DoR)	DoR will be calculated as the median of the maximum tumor shrinkage rates.	Up to 3 years
Primary	Response rate (RR) by response evaluation criteria in solid tumors (RECIST v1.1)	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.	Up to 18 months
Secondary	Time to treatment failure (TTF)	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.	Up to 18 months
Secondary	Progression-free survival (PFS)	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.	Up to 3 years
Secondary	Overall survival (OS)	OS is defined as the time from date of starting treatment until date of death from any cause.	Up to 3 years
Secondary	R0 resection rate	R0 resection rate will be calculated as the ratio of the number of eligible patients who experienced a complete (R0) resection.	Up to 18 months
Secondary	Relative dose intensity (RDI)	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.	Up to 18 months
Secondary	Incidence of adverse events		Up to 3 years