NCT02350530

Brief Summary

BACKGROUND: For patients with liver-limited metastatic colorectal cancer (mCRC), complete resection of liver metastases is the only potentially curative treatment. The current goal of medical treatment for colorectal cancer with initially unresectable liver metastases is to maximize the rate of secondary resection and prolong overall survival (OS). A strong correlation was found between response rate and secondary resection rate of metastases, and the triple drugs combination of infusional 5-fluorouracil/leucovorin (5-FU/LV), irinotecan, and oxaliplatin (FOLFOXIRI) was recommended can be used in selected patients with potentially resectable metastases in order to improve response rate and make resection more possible. The addition of a anti-VEGFs monoclonal antibody such as bevacizumab to chemotherapy has been shown to increase response rate, resection rate and improve OS in the first-line treatment of mCRC patients. The efficacy and safety of bevacizumab in addition to triplet drugs were previously tested in OLIVIA trial, the resection rate of liver metastases of 49% was reported, and the response rate was 81%; most common grade 3-4 adverse events was neutropenia. On the basis of such promising results, we conducted the present randomized study to explore whether FOLFOXIRI plus bevacizumab compared with FOLFOXIRI alone as first-line treatment could improve radical resectability in patients with RAS mutation-type, unresectable liver-only metastatic colorectal cancer. OBJECTIVE: The primary objective of the FOBULM study is to evaluate the efficacy of FOLFOXIRI plus bevacizumab compared to FOLFOXIRI alone in patients with initially unresectable liver-limited RAS mutation-type mCRC. Secondary objectives are safety and tolerability of the treatment, efficacy in terms of objective response rate (ORR), OS, progression free survival (PFS), quality of life and an assessment of biomarkers for predictive response and prognosis.

Trial Health

43
At Risk

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Trial has exceeded expected completion date
Enrollment
138

participants targeted

Target at P75+ for phase_2

Timeline
Completed

Started Jan 2015

Longer than P75 for phase_2

Geographic Reach
1 country

1 active site

Status
unknown

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

January 1, 2015

Completed
23 days until next milestone

First Submitted

Initial submission to the registry

January 24, 2015

Completed
5 days until next milestone

First Posted

Study publicly available on registry

January 29, 2015

Completed
2.9 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

January 1, 2018

Completed
2 years until next milestone

Study Completion

Last participant's last visit for all outcomes

January 1, 2020

Completed
Last Updated

September 20, 2016

Status Verified

September 1, 2016

Enrollment Period

3 years

First QC Date

January 24, 2015

Last Update Submit

September 19, 2016

Conditions

Metastatic Colorectal Cancer

Keywords

Colorectal cancerMetastatic colorectal cancerLiver metastasesLiver resectionLiver ablationConversion therapyFOLFOXIRIOxaliplatinIrinotecanFluorouracilBevacizumabRAS mutation

Outcome Measures

Primary Outcomes (1)

  • The conversion rate of liver metastases

    Defined as the proportion of patients who had a curative liver treatment following protocol treatment, i.e., liver metastases that can be radical resected with or without ablation with no postoperative evidence of residual malignant disease.

    8 months

Secondary Outcomes (5)

  • Toxicity assessed using the NCI common toxicity criteria, version 4.0.

    8 months

  • Response rate

    8 months

  • Overall survival time

    5 years

  • Progression free survival

    2 years

  • Quality of life (QLQ C30)

    Every 2 weeks after the first treatment until 6 months

Study Arms (2)

A (FOLFOXIRI + Bevacizumab)

EXPERIMENTAL

FOLFOXIRI + Bevacizumab

Drug: FOLFOXIRI + Bevacizumab

B (FOLFOXIRI)

ACTIVE COMPARATOR

FOLFOXIRI

Drug: FOLFOXIRI

Interventions

FOLFOXIRI + BevacizumabDRUG

Bevacizumab 5mg/kg + irinotecan\* 165 mg/m² + oxaliplatin 85 mg/m² + leucovorin 200 mg/m² + 5-FU 2800 mg/m² cont. inf. 46h all on day 1 of each 2 weeks cycle until PD or resectability or to max. 12 cycles

Also known as: Bevacizumab, Irinotecan, Oxaliplatin, 5-Fluorouracil
A (FOLFOXIRI + Bevacizumab)
FOLFOXIRIDRUG

Irinotecan\* 165 mg/m² + oxaliplatin 85 mg/m² + leucovorin 200 mg/m² + 5-FU 2800 mg/m² cont. inf. 46h all on day 1 of each 2 weeks cycle until PD or resectability or to max. 12 cycles

Also known as: Irinotecan, Oxaliplatin, 5-Fluorouracil
B (FOLFOXIRI)

Eligibility Criteria

Age18 Years - 70 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Willing and able to provide written informed consent
  • Histological or cytological documentation of adenocarcinoma of the colon or rectum.
  • Male or female subjects \> 18 years \< 70 of age.
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
  • There must be documentation by CT scan, MRI, or intraoperative palpation that the patient has evidence of metastases confined to the liver.
  • The liver metastases must have been assessed by multidisciplinary team including hepatic surgeon approved to participate in the study to be unresectable based on at least one of the four criteria: 1. All of the liver metastases can not be completed resected with negative margins; 2. No ability to preservation of two contiguous hepatic segments; 3. No ability to preservation of adequate vascular inflow and outflow as well as biliary drainage; 4. Complete resection would require greater than 70% of the liver parenchyma to be removed.
  • The colorectal primary tumor or metastatic tumor must be determined to be KRAS (exon 2 at codon 12 and 13; exon 3 at codon 59 and 61; exon 4 at codon 117 and 146) or NRAS (exon 2 at codon 12 and 13; exon 3 at codon 59 and 61; exon 4 at codon 117 and 146) mutation-type.
  • Primary tumor and regional nodes were resected with clear surgical margins or; unresected primary tumor with plan to radical resect the primary tumor.
  • No previous any systemic anticancer therapy for metastatic disease (adjuvant chemotherapy for non-metastatic disease is allowed if terminated more than 6 months ago).
  • Adequate bone marrow, hepatic and renal function as assessed by the following laboratory requirements conducted within 7 days of starting study treatment: Hemoglobin (Hb) ≥ 90g/ L, absolute neutrophil count (ANC) ≥ 1.5×109/ L, platelet count ≥ 100×109/ L; Total bilirubin ≤ 1.5×the upper limit of normal (ULN), alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 5 ×ULN; Serum creatinine ≤1.5×the ULN.

You may not qualify if:

  • Any evidence of extrahepatic metastases, lymph node (including portal lymph nodes) metastases and primary tumor recurrence.
  • Previous hepatic resection and/or ablation, hepatic arterial infusion therapy, radiation therapy to the liver.
  • Previous or concurrent cancer that is distinct in primary site or histology from colorectal cancer within 5 years prior to randomization.
  • Significant cardiovascular disease including unstable angina or myocardial infarction within 6 months before initiating study treatment.
  • Heart failure grade III/IV (NYHA-classification).
  • Unresolved toxicity higher than CTCAE v.4.0 Grade 1 attributed to any prior therapy/procedure.
  • Subjects with known allergy to the study drugs or to any of its excipients.
  • Current or recent (within 4 weeks prior to starting study treatment) treatment of another investigational drug or participation in another investigational study.
  • Breast- feeding or pregnant women
  • Lack of effective contraception.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

The Sixth Affiliated Hospital of Sun Yat-sen University

Guangzhou, Guangdong, 510655, China

RECRUITING

MeSH Terms

Conditions

Colorectal Neoplasms

Interventions

BevacizumabIrinotecanOxaliplatinFluorouracilFOLFOXIRI protocol

Condition Hierarchy (Ancestors)

Intestinal NeoplasmsGastrointestinal NeoplasmsDigestive System NeoplasmsNeoplasms by SiteNeoplasmsDigestive System DiseasesGastrointestinal DiseasesColonic DiseasesIntestinal DiseasesRectal Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, HumanizedAntibodies, MonoclonalAntibodiesImmunoglobulinsImmunoproteinsBlood ProteinsProteinsAmino Acids, Peptides, and ProteinsSerum GlobulinsGlobulinsCamptothecinAlkaloidsHeterocyclic CompoundsCoordination ComplexesOrganic ChemicalsUracilPyrimidinonesPyrimidinesHeterocyclic Compounds, 1-Ring

Study Officials

  • Yanhong Deng, M.D.

    Sixth Affiliated Hospital, Sun Yat-sen University

    PRINCIPAL INVESTIGATOR

Central Study Contacts

Yanhong Deng, M.D.

CONTACT

00861392510652513925106525@163.com

Study Design

Study Type
interventional
Phase
phase 2
Allocation
NON RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Associate professor

Study Record Dates

First Submitted

January 24, 2015

First Posted

January 29, 2015

Study Start

January 1, 2015

Primary Completion

January 1, 2018

Study Completion

January 1, 2020

Last Updated

September 20, 2016

Record last verified: 2016-09

Locations

CN(1)