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

Primary Purpose

Metastatic Colorectal Cancer

Status

Completed

Phase

Phase 2

Locations

Japan

Study Type

Interventional

Intervention

Oxaliplatin (L-OHP)

Irinotecan hydrochloride hydrate (CPT-11)

Continuous intravenous infusion of fluorouracil (CIV 5-FU)

Levofolinate calcium (l-LV)

Bevacizumab (Bmab)

About this trial

This is an interventional treatment trial for Metastatic Colorectal Cancer focused on measuring bevacizumab, oxaliplatin, irinotecan, hydrochloride hydrate, fluorouracil, levofolinate calcium

Eligibility Criteria

20 Years - 70 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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/*28.
The Eastern Cooperative Oncology Group (ECOG) performance status of =<1.
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.
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.

Sites / Locations

Matsuyama Red Cross Hospital
Kagawa University Hospital
Kawasaki Medical School Hospital
Okayama Saiseikai General Hospital
Okayama University Hospital
Okayama Rosai Hospital
Tokushima Red Cross Hospital

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Treatment Arm

Arm 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.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.

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.

Overall survival (OS)

OS is defined as the time from date of starting treatment until date of death from any cause.

R0 resection rate

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)

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

Full Information

NCT ID

NCT02497157

First Posted

June 25, 2015

Last Updated

June 16, 2020

Sponsor

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

Collaborators

Hiroshima Prefectural Hospital, National Hospital Organization Shikoku Cancer Center

1. Study Identification

Unique Protocol Identification Number

NCT02497157

Brief Title

Bevacizumab + Triplet Treatment for Untreated With Chemotherapy Metastatic Colorectal Cancer

Acronym

BeTRI

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

June 2020

Overall Recruitment Status

Completed

Study Start Date

May 21, 2015 (Actual)

Primary Completion Date

June 2019 (Actual)

Study Completion Date

June 2019 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

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

Collaborators

Hiroshima Prefectural Hospital, National Hospital Organization Shikoku Cancer Center

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Metastatic Colorectal Cancer

Keywords

bevacizumab, oxaliplatin, irinotecan, hydrochloride hydrate, fluorouracil, levofolinate calcium

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

45 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Treatment Arm

Arm Type

Experimental

Arm Description

Intervention Type

Drug

Intervention Name(s)

Oxaliplatin (L-OHP)

Intervention Type

Drug

Intervention Name(s)

Irinotecan hydrochloride hydrate (CPT-11)

Intervention Type

Drug

Intervention Name(s)

Continuous intravenous infusion of fluorouracil (CIV 5-FU)

Intervention Type

Drug

Intervention Name(s)

Levofolinate calcium (l-LV)

Intervention Type

Drug

Intervention Name(s)

Bevacizumab (Bmab)

Primary Outcome Measure Information:

Title

Response rate (RR) by response evaluation criteria in solid tumors (RECIST v1.1)

Description

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.

Time Frame

Up to 18 months

Secondary Outcome Measure Information:

Title

Time to treatment failure (TTF)

Description

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.

Time Frame

Up to 18 months

Title

Progression-free survival (PFS)

Description

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 Frame

Up to 3 years

Title

Overall survival (OS)

Description

OS is defined as the time from date of starting treatment until date of death from any cause.

Time Frame

Up to 3 years

Title

R0 resection rate

Description

R0 resection rate will be calculated as the ratio of the number of eligible patients who experienced a complete (R0) resection.

Time Frame

Up to 18 months

Title

Relative dose intensity (RDI)

Description

Time Frame

Up to 18 months

Title

Incidence of adverse events

Time Frame

Up to 3 years

Other Pre-specified Outcome Measures:

Title

Early tumor shrinkage (ETS) rates in 8 weeks after starting the treatment, evaluated by RECIST v1.1

Description

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.

Time Frame

Baseline (week 0), week 8

Title

Deepness of response (DoR)

Description

DoR will be calculated as the median of the maximum tumor shrinkage rates.

Time Frame

Up to 3 years

10. Eligibility

Sex

All

Minimum Age & Unit of Time

20 Years

Maximum Age & Unit of Time

70 Years

Accepts Healthy Volunteers

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/*28. The Eastern Cooperative Oncology Group (ECOG) performance status of =<1. 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. 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.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Katsunori Shinozaki, MD, Ph.D.

Organizational Affiliation

Hiroshima Prefectural Hospital

Official's Role

Principal Investigator

First Name & Middle Initial & Last Name & Degree

Tomohiro Nishina, MD, Ph.D.

Organizational Affiliation

National Hospital Organization Shikoku Cancer Center

Official's Role

Principal Investigator

Facility Information:

Facility Name

Matsuyama Red Cross Hospital

City

Matsuyama-city

State/Province

Ehime-prefecture

ZIP/Postal Code

790-8524

Country

Japan

Facility Name

Kagawa University Hospital

City

Kita-gun, Miki-cho

State/Province

Kagawa-prefecture

ZIP/Postal Code

761-0793

Country

Japan

Facility Name

Kawasaki Medical School Hospital

City

Kurashiki-city

State/Province

Okayama-prefecture

ZIP/Postal Code

701-0192

Country

Japan

Facility Name

Okayama Saiseikai General Hospital

City

Okayama-city

State/Province

Okayama-prefecture

ZIP/Postal Code

700-8511

Country

Japan

Facility Name

Okayama University Hospital

City

Okayama-city

State/Province

Okayama-prefecture

ZIP/Postal Code

700-8558

Country

Japan

Facility Name

Okayama Rosai Hospital

City

Okayama-city

State/Province

Okayama-prefecture

ZIP/Postal Code

702-8055

Country

Japan

Facility Name

Tokushima Red Cross Hospital

City

Komatsushima-city

State/Province

Tokushima-prefecture

ZIP/Postal Code

773-8502

Country

Japan

12. IPD Sharing Statement

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Bevacizumab + Triplet Treatment for Untreated With Chemotherapy Metastatic Colorectal Cancer

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