The Efficacy of Bevacizumab Combined With m-FOLFOXIRI in Borderline Resectable Colorectal Liver Metastases

NCT03711240 | Unknown Phase 2 DMC

• 1 other identifier: IIT-10
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

This single-arm study will evaluate the resection rate of liver metastases in patients with metastatic colorectal cancer and borderline unresectable liver metastases receiving treatment with bevacizumab in combination with modified-FOLFOXIRI as first line treatment. Patients will receive bevacizumab (5 mg/kg) plus modified-FOLFOXIRI (irinotecan 150 mg/m2, oxaliplatin 85 mg/m2, leucovorin 200 mg/m2, and fluorouracil 2400 mg/m2 as a 46-h continuous infusion) every 14 days as neoadjuvant chemotherapy regimen. This study treatment will continue until surgery, disease progression, unacceptable toxicity, or patient refusal.

Conditions

Colorectal Cancer

Keywords

colorectal liver metastases; FOLFOXIRI; bevacizumab

Outcome Measures

Primary Outcomes (1)

• Resection rate of liver metastases

  The percentage of the number of subjects with R0 and R1 resection after treatment.

  6 months

Secondary Outcomes (4)

• Tumor response rate

  6 months

• Progression free survival

  5 years

• Overall survival

  5 years

• Percentage of adverse effects related to combination treatment

  5 years

Study Arms (1)

bevacizumab+mFOLFOXIRI

EXPERIMENTAL

Drug: bevacizumab; Drug: Oxaliplatin; Drug: Irinotecan; Drug: Leucovorin; Drug: 5-FU

Interventions

bevacizumab DRUG

5mg/kg iv day 1 every 2 weeks

bevacizumab+mFOLFOXIRI

Oxaliplatin DRUG

85mg/m2 2-hour iv infusion, day 1 every 2 weeks

bevacizumab+mFOLFOXIRI

Irinotecan DRUG

150mg/m2 1.5-hour iv infusion, day 1 every 2 weeks

bevacizumab+mFOLFOXIRI

Leucovorin DRUG

200mg/m2 2-hour iv infusion, day 1 every 2 weeks

bevacizumab+mFOLFOXIRI

5-FU DRUG

2400mg/m2 46-hour continuous iv infusion, day 1 every 2 weeks

bevacizumab+mFOLFOXIRI

Eligibility Criteria

• Age: 20 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically proven diagnosis of colorectal cancer.
• Borderline resectable liver metastases of colorectal cancer considered to have poor-risk disease not deemed to be suitable for upfront resection if they had one or more of the following features assessed by a local multidisciplinary team: more than four metastases, any liver lesion with diameter \>5 cm, location and distribution of metastatic disease within the liver unsuitable for resection with clear margins (e.g. involvement of both lobes of liver, invasion of intrahepatic vascular structures), extent of liver involvement precluding resection with adequate post-resection residual liver parenchyma volume for viable liver function in the immediate postoperative period, and inability to retain adequate vascular inflow and outflow to maintain viable liver function.
• At least one measurable lesion according to RECIST criteria.
• Age 20-75 years.
• ECOG performance \< 1 if age \< 70 years, ECOG PS = 0 if age = 70-75 years.
• Life expectancy of at least 12 weeks.
• Neutrophils ≥1.5 x 109/L, Platelets≥ 100 x 109/L, Hgb ≥10 g/dl.
• Total bilirubin ≤1.5 time the upper-normal limits (UNL) of the Institutional normal values and ASAT (SGOT) and/or ALAT (SGPT) ≤5 x UNL, alkaline phosphatase ≤5 x UNL.
• Serum creatinine≤ 1.5 x UNL.
• Patients discovered to have proteinuria on urinalysis at baseline, should undergo a 24-hour urine collection and must demonstrate ≤1 g of protein/24 hr.
• Written informed consent.

You may not qualify if:

• Prior neoadjuvant or adjuvant chemotherapy completed \<6 months.
• Prior chemotherapy for metastatic disease.
• Any extrahepatic metastases.
• History or evidence upon physical examination of CNS disease unless adequately treated (e.g., seizure not controlled with standard medical therapy or history of stroke).
• Serious, non-healing wound, ulcer, or bone fracture.
• Evidence of bleeding diathesis or coagulopathy.
• Uncontrolled hypertension.
• Clinically significant (i.e. active) cardiovascular disease for example cerebrovascular accidents (≤6 months), myocardial infarction (≤ 6 months), unstable angina, New York Heart Association (NYHA) grade II or greater congestive heart failure, serious cardiac arrhythmia requiring medication.
• Current or recent (within 10 days prior to study treatment start) ongoing treatment with anticoagulants for therapeutic purposes.
• Chronic daily treatment with aspirin .
• Patients with known allergy to Chinese hamster ovary cell proteins, or any of the components of the study medications.
• Other co-existing malignancies or malignancies diagnosed within the last 5 years with the exception of sin basal cell carcinoma or cervical cancer in situ.
• Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to study treatment start, or anticipation of the need for major surgical procedure during the course of the study.
• Other severe systemic diseases without stable medical control.
• Pregnant or lactating women.

Sponsors & Collaborators

• National Cheng-Kung University Hospital: lead

Study Sites (1)

National Cheng-Kung University Hospital

Tainan, Taiwan

RECRUITING

MeSH Terms

Conditions

Colorectal Neoplasms

Interventions

Bevacizumab; Oxaliplatin; Irinotecan; Leucovorin; Fluorouracil

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; Coordination Complexes; Organic Chemicals; Camptothecin; Alkaloids; Heterocyclic Compounds; Formyltetrahydrofolates; Tetrahydrofolates; Folic Acid; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Coenzymes; Enzymes and Coenzymes; Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring

Study Officials

• Shang Hung Chen

  National Health Research Institutes, Taiwan

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Jean Yang

CONTACT

+886-6-7000123; JeanYang@nhri.org.tw

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: October 12, 2018
• First Posted: October 18, 2018
• Study Start: January 8, 2019
• Primary Completion: October 30, 2020
• Study Completion: October 30, 2020
• Last Updated: March 13, 2019

Record last verified: 2019-03

Data Sharing

• IPD Sharing: Will not share

Locations

TW (1)