A Translational Study of Bevacizumab in Participants With Metastatic Colorectal Cancer

NCT01588990 | Completed Phase 4 Results

• 1 other identifier: ML25753
• Study Type: interventional
• Target: 128
• Locations: 1 country
• Sites: 17

Brief Summary

This open-label, prospective, single-arm, multicenter study will evaluate the relationship of the markers of inflammation and progression-free survival (PFS) in participants with previously untreated metastatic colorectal cancer. The study consists of two phases: Phase A treatment: oral capecitabine plus infusional oxaliplatin (XELOX) plus bevacizumab, or modified infusional 5-fluorouracil (5-FU), leucovorin (LV) and oxaliplatin (mFOLFOX6) plus bevacizmab administered until first disease progression. Participants will then continue with Phase B treatment: infusional 5-FU, LV and irinotecan (FOLFIRI) plus bevacizumab until second disease progression. The anticipated time on study treatment is 4 years.

Conditions

Colorectal Neoplasms

Outcome Measures

Primary Outcomes (1)

• Association Between Neutrophil to Lymphocyte Ratio (NLR) [NLR ≤5 Versus NLR >5] and Progression-Free Survival (PFS) as Assessed by Hazard Ratio

  NLR was calculated from the laboratory values as the ratio of Neutrophils to Lymphocytes. PFS was defined as the time from the start of initial treatment to documentation of first disease progression or death from any cause, whichever occurred first. Disease progression was determined according to standard practice based on radiological, biochemical (carcinoembryonic antigen \[CEA\]) or clinical factors. Determination of disease progression was to be unequivocal and was defined as any of the following: an unequivocal and clinically meaningful increase in the size of known tumors, the appearance of one or more new lesions, death due to disease without prior objective documentation of progression, elevated CEA accompanied by other radiological or clinical evidence of progression, or symptomatic deterioration. The association between NLR (NLR less than or equal to \[≤\] 5 vs greater than \[\>\] 5) and PFS was reported as hazard ratio.

  Baseline up to disease progression, death or end of study (up to 4 years)

Secondary Outcomes (21)

• PFS Until First Disease Progression as Assessed by the Investigator Based on Routine Clinical Practice: Phase A

  Baseline up to first disease progression, death or end of study (up to 4 years)

• PFS Until Second Disease Progression as Assessed by the Investigator Based on Routine Clinical Practice: Phase B

  From the start of Phase B treatment to disease progression, death or end of study (up to 4 years)

• Time to Failure of Strategy (TFS): Overall

  Baseline up to disease progression, death or end of study (up to 4 years)

• Duration of Disease Control (DDC) as Assessed by the Investigator Based on Routine Clinical Practice: Overall

  Baseline up to disease progression, death or end of study (up to 4 years)

• Overall Survival (OS) From the Start of Treatment to Study Completion: Overall

  Baseline until death or end of study (up to 4 years)

Study Arms (1)

Bevacizumab: Phase A and Phase B

EXPERIMENTAL

The trial will consist of 2 phases of treatment. Phase A: Participants will receive bevacizumab 7.5 mg/kg intravenous (IV) infusion on Day 1 every 3 weeks in combination with XELOX (capecitabine and oxaliplatin) or bevacizumab 5 mg/kg IV on Day 1 every 2 weeks in combination with mFOLFOX6 (oxaliplatin, leucovorin, and 5-fluouracil) until first disease progression or occurrence of unmanageable toxicity. Phase B: Upon documented first disease progression, participants will continue receiving bevacizumab 5 mg/kg IV on Day 1 every 2 weeks in combination with FOLFIRI (irinotecan, leucovorin, and 5-fluouracil) until second disease progression or occurrence of unmanageable toxicity. Phase B treatment should commence within 4 weeks of the date of documented first disease progression.

Drug: Oxaliplatin; Drug: Capecitabine; Drug: Bevacizumab; Drug: Leucovorin; Drug: 5-Fluouracil; Drug: Irinotecan

Interventions

Oxaliplatin DRUG

Participants will receive oxaliplatin 85 milligrams per square meter (mg/m\^2) IV infusion on Day 1 of every 2 weeks cycle during alternative Phase A treatment or 130 mg/m\^2 on Day 1 of every 3 weeks cycle during Phase A treatment.

Bevacizumab: Phase A and Phase B

Capecitabine DRUG

Participants will receive capecitabine 1000 mg/m\^2 per oral (PO) twice daily on Days 1-14 of 3 weeks cycle during Phase A treatment.

Bevacizumab: Phase A and Phase B

Bevacizumab DRUG

Participants will receive 7.5 mg/kg IV infusion on Day 1 every 3 weeks (Phase A treatment) or 5 mg/kg IV on Day 1 every 2 weeks (Alternative Phase A treatment and Phase B).

Also known as: Avastin, RO4876646

Bevacizumab: Phase A and Phase B

Leucovorin DRUG

Participants will receive leucovorin 400 mg/m\^2 IV on Day 1 every 2 weeks (Alternative Phase A treatment and Phase B). Investigators may elect to chose low dose of leucovorin (either 20 mg/m\^2 or 50 mg total dose).

Bevacizumab: Phase A and Phase B

5-Fluouracil DRUG

Participants will receive 5-fluouracil loading dose of 400 mg/m\^2 IV on Day 1 followed by 2400 mg/m\^2 continuous IV infusion over 46 hours Day 1 (Alternative Phase A treatment and Phase B).

Bevacizumab: Phase A and Phase B

Irinotecan DRUG

Participants will receive irinotecan 180 mg/m\^2 IV on Day 1 every 2 weeks during Phase B treatment.

Bevacizumab: Phase A and Phase B

Eligibility Criteria

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

You may qualify if:

• For resected primary tumor participants, and participants with primary tumor in situ:
• Previously untreated metastatic colorectal cancer and not a candidate for curative resection
• World Health Organization (WHO) performance status of 0-1
• Life expectancy of greater than or equal to (\>/=) 3 months
• Eligible for XELOX, mFOLFOX6, FOLFIRI and bevacizumab treatment in accordance with local standards of care and pharmaceutical benefits scheme guidelines
• Intact primary tumor of the colon or the rectum not requiring surgical intervention prior to study start
• Minimal or asymptomatic primary tumor

You may not qualify if:

• Resected primary tumor participants, and participants with primary tumor in situ:
• Previous chemotherapy for metastatic colorectal cancer
• Previous neoadjuvant or adjuvant chemotherapy less than 6 months prior to study start
• Radiotherapy within 28 days prior to enrollment or not recovered from a radiotherapy
• History of non-colorectal cancer (participants are eligible if disease-free for \>/=5 years and the risk of recurrence is deemed low)
• Presence of active inflammatory bowel disease
• History of gastrointestinal perforations
• Peritoneal disease
• History of significant bleeding event
• Significant vascular disease
• Peripheral arterial thrombosis or other thrombotic event within 6 months before study start
• Prior endoscopic management of the current tumor
• Acute diverticulitis
• Presence of intra-abdominal abscess
• Active gastroduodenal ulcer

Sponsors & Collaborators

• Hoffmann-La Roche: lead

Study Sites (17)

Canberra Hospital

Garran, Australian Capital Territory, 2605, Australia

Location

Macarthur Cancer Therapy Centre

Campbelltown, New South Wales, 2560, Australia

Location

Chris O'Brien Lifehouse

Camperdown, New South Wales, 2050, Australia

Location

St Vincent'S Hospital; Clinical Oncology

Darlinghurst, New South Wales, 2010, Australia

Location

Mid North Coast Cancer Institute

Port Macquarie, New South Wales, 2444, Australia

Location

Royal North Shore Hospital; Department of Medical Oncology

St Leonards, New South Wales, 2065, Australia

Location

Sydney Adventist Hospital; Clinical Trial Unit

Sydney, New South Wales, 2076, Australia

Location

Royal Brisbane Hospital

Brisbane, Queensland, 4029, Australia

Location

Rockhampton Hospital

Rockhampton, Queensland, 4700, Australia

Location

The Townsville Hospital; Townsville Cancer Centre

Townsville, Queensland, 4812, Australia

Location

Lyell McEwin Hospital; Oncology Clinical Trials, Chemotherapy Day Unit

Elizabeth Vale, South Australia, 5112, Australia

Location

Calvary North Adelaide; North Adeliade Oncology Centre

North Adelaide, South Australia, 5006, Australia

Location

Launceston General Hospital

Launceston, Tasmania, 7250, Australia

Location

Austin Hospital; Medical Oncology

Heidelberg, Victoria, 3084, Australia

Location

Sunshine Hospital; Oncology Research

St Albans, Victoria, Australia

Location

St John of God Murdoch Hospital; Oncology West

Murdoch, Western Australia, 6150, Australia

Location

St John of God Hospital; Bendat Cancer Centre

Subiaco, Western Australia, 6008, Australia

Location

Related Publications (2)

• Clarke SJ, Burge M, Feeney K, Gibbs P, Jones K, Marx G, Molloy MP, Price T, Reece WHH, Segelov E, Tebbutt NC. The prognostic role of inflammatory markers in patients with metastatic colorectal cancer treated with bevacizumab: A translational study [ASCENT]. PLoS One. 2020 Mar 6;15(3):e0229900. doi: 10.1371/journal.pone.0229900. eCollection 2020.

  PMID: 32142532 DERIVED

• Clarke S, Burge M, Cordwell C, Gibbs P, Reece W, Tebbutt N. An Australian translational study to evaluate the prognostic role of inflammatory markers in patients with metastatic ColorEctal caNcer Treated with bevacizumab (Avastin) [ASCENT]. BMC Cancer. 2013 Mar 15;13:120. doi: 10.1186/1471-2407-13-120.

  PMID: 23497305 DERIVED

MeSH Terms

Conditions

Colorectal Neoplasms

Interventions

Oxaliplatin; Capecitabine; Bevacizumab; Leucovorin; Irinotecan

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)

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

Results Point of Contact

• Title: Medical Communications
• Organization: Hoffmann-La Roche

genentech@druginfo.com

800-821-8590

Study Officials

• Clinical Trials

  Hoffmann-La Roche

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 27, 2012
• First Posted: May 1, 2012
• Study Start: June 26, 2012
• Primary Completion: September 15, 2016
• Study Completion: September 30, 2016
• Last Updated: January 22, 2019
• Results First Posted: January 22, 2019

Record last verified: 2018-08

Locations

AU (17)