A Multicenter, Clinical Study of FOLFOXIRI With Bevacizumab As First-line Therapy in Patients With mCRC

NCT02246049 | Completed Phase 2 DMC

• 1 other identifier: QUATTRO
• Study Type: interventional
• Target: 69
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study to assess efficacy and tolerability of combination therapy FOLFOXIRI with Bevacizumab (BV) as a first-line therapy in patients with metastatic colorectal cancer.

Conditions

Colorectal Neoplasms

Keywords

Metastatic colorectal cancer, bevacizumab, FOLFOXIRI

Outcome Measures

Primary Outcomes (1)

• Progression-free survival (PFS) at 10 months

  PFS by investigator-reported measurements according to CT image. PFS was calculated from the day of treatment start to the first observation of progression disease (PD) or death from any cause. PD was defined as Overall Response by RECIST criteria v1.1 according to CT image.

  PFS rate at 10 months from study entry

Secondary Outcomes (10)

• Response rate (RR) by central review.

  Up to 18 months

• Response rate (RR) by investigator-reported measurements.

  Up to 30 months

• PFS by central review according to CT image.

  Up to 18 months

• Overall survival (OS)

  Up to 30 months

• Efficacy by RAS status ; RR,PFS,OS

  Up to 30 months

Study Arms (1)

FOLFOXIRI plus bevacizumab

EXPERIMENTAL

Induction therapy is followed by the maintenance therapy. \[Induction treatment:FOLFOXIRI plus bevacizumab\] Administered for a maximum of 12 cycles. BV: 5mg/kg (d.i.v.) L-OHP: 85 mg/sq.m (d.i.v.) CPT-11:165mg/sq.m (d.i.v.) l-LV:200mg/sq.m (d.i.v.) 5-FU:3,200mg/sq.m (c.i.v.) Administered every 2 weeks. \[Maintenance treatment:5-FU / I-LV plus bevacizumab\] BV:5mg/kg (d.i.v.) l-LV:200mg/sq.m (d.i.v.) 5-FU:3,200mg/sq.m (c.i.v.) Administered every 2 weeks.

Biological: Bevacizumab; Drug: 5-fluorouracil; Drug: Irinotecan hydrochloride; Drug: Leucovorin calcium; Drug: Oxaliplatin

Interventions

Bevacizumab BIOLOGICAL

Given IV

Also known as: BV

FOLFOXIRI plus bevacizumab

5-fluorouracil DRUG

Given IV

Also known as: 5-FU

FOLFOXIRI plus bevacizumab

Irinotecan hydrochloride DRUG

Given IV

Also known as: CPT-11

FOLFOXIRI plus bevacizumab

Leucovorin calcium DRUG

Given IV

Also known as: I-LV

FOLFOXIRI plus bevacizumab

Oxaliplatin DRUG

Given IV

Also known as: L-OHP

FOLFOXIRI plus bevacizumab

Eligibility Criteria

• Age: 20 Years - 75 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Written Informed consent.
• Histopathologically proven diagnosis of colorectal cancer (adenocarcinoma) excluding vermiform appendix cancer and proctos cancer.
• Not resectable metastatic colorectal cancer
• Age at enrollment is \>= 20 and \<= 75 years
• ECOG PS \< 2 if age \< 70 years, ECOG PS = 0 if age = 71-75 years
• One or more measurable lesion in RECIST ver.1.1 criteria according to contrast enhanced CT chest / abdomen / pelvis diagnosis.
• Not previously treated with chemotherapy. ( Previous adjuvant by fluoropyrimidine monotherapy is allowed if more than 24 weeks have elapsed between the end of adjuvant therapy and first relapse.)
• Vital organ functions (listed below) are preserved within 2 weeks prior to entry. Data recorded nearest to the entry should be referred. Blood transfusion or erythropoiesis stimulating agents less than 2 weeks prior to the tests are not allowed.
• Neu. \>= 1,500/cubicmillimeter Pt. \>= 100,000/cubicmillimeter Hb. \>= 9.0 g/dL T-bil. \<= upper limit of normal (ULN)\*1.5 AST and ALT,ALP \<= upper limit of normal (ULN)\*2.5 (\<= ULN\*5 in case of liver metastasis) Serum creatinine \<= upper limit of normal (ULN) \*1.5 PT-INR \< 1.5 Proteinuria \<= 2+
• UGT1A1 genotype tested. Categorized into Wild or single Hetero.

You may not qualify if:

• Previously treated with irradiation to bone marrow constituting 20% or more of irradiation field.
• Untreated brain metastases or spinal cord compression or primary brain tumors.
• History of CNS disease.\[except for asymptomatic Lacunar stroke\]
• Requiring chronic systemic corticosteroid treatment.
• Current or recent ongoing treatment with anticoagulants.
• Clinically significant cardiovascular disease for example cerebrovascular accidents, myocardial infarction, unstable angina, congestive heart failure, serious cardiac arrhythmia requiring medication.
• Treatment with any investigational drug within 4 weeks.
• Patient with Uncontrolled hypertension, Uncontrolled diabetes, Uncontrolled diarrhea, \>=grade 1 peripheral neuropathy, Active peptic ulcer, Non-healing wound, Clinically important diseases.
• Major surgical procedure within 28 days prior to study treatment start, open biopsy, or significant traumatic injury, or anticipation of the need for major surgical procedure.\[except for implantation of central venous catheter and port system.\]
• Lack of physical integrity of the upper gastrointestinal tract.
• Pregnant women, lactating woman , positive by pregnancy test , wishing to become pregnant, and Sexually active males.
• Hepatitis B or hepatitis C. Evidence of HIV infection.
• Previous Chemotherapy for other organs.
• Other active co-existing malignancies.
• History / Presence of thrombosis within 1 year requiring medication.

Sponsors & Collaborators

• EPS Corporation: lead

Study Sites (1)

EPS Corporation

Shinjuku, Tokyo, 162-0814, Japan

Location

MeSH Terms

Conditions

Colorectal Neoplasms

Interventions

Bevacizumab; Fluorouracil; Irinotecan; Leucovorin; Oxaliplatin

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Camptothecin; Alkaloids; Formyltetrahydrofolates; Tetrahydrofolates; Folic Acid; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Coenzymes; Enzymes and Coenzymes; Coordination Complexes; Organic Chemicals

Study Officials

• Takeshi Kato, M.D., Ph.D

  Department of Surgery, National Hospital Organization Osaka National Hospital.

  PRINCIPAL INVESTIGATOR

• Akiyoshi Kanazawa, M.D., Ph.D

  Department of Surgery, Shimane Prefectural Central Hospital.

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 12, 2014
• First Posted: September 22, 2014
• Study Start: May 1, 2014
• Primary Completion: February 1, 2017
• Study Completion: February 1, 2017
• Last Updated: June 19, 2017

Record last verified: 2017-06

Locations

JP (1)