A Translational Study of Bevacizumab in Participants With Metastatic Colorectal Cancer

NCT ID: NCT01588990

Last Updated: 2019-01-22

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 128 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-06-26
• Study Completion Date: 2016-09-30

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

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Bevacizumab: Phase A and Phase B

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.

Group Type: EXPERIMENTAL

Oxaliplatin

Intervention Type: 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.

Capecitabine

Intervention Type: 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

Intervention Type: 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).

Leucovorin

Intervention Type: 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).

5-Fluouracil

Intervention Type: 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).

Irinotecan

Intervention Type: DRUG

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

Interventions

Oxaliplatin

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.

Intervention Type: DRUG

Capecitabine

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.

Intervention Type: DRUG

Bevacizumab

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).

Intervention Type: DRUG

Leucovorin

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).

Intervention Type: DRUG

5-Fluouracil

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).

Intervention Type: DRUG

Irinotecan

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

Intervention Type: DRUG

Other Intervention Names

Avastin, RO4876646

Eligibility Criteria

Inclusion Criteria

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

Exclusion Criteria

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Hoffmann-La Roche

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Clinical Trials

Role: STUDY_DIRECTOR

Hoffmann-La Roche

Locations

Canberra Hospital

Garran, Australian Capital Territory, Australia

Macarthur Cancer Therapy Centre

Campbelltown, New South Wales, Australia

Chris O'Brien Lifehouse

Camperdown, New South Wales, Australia

St Vincent'S Hospital; Clinical Oncology

Darlinghurst, New South Wales, Australia

Mid North Coast Cancer Institute

Port Macquarie, New South Wales, Australia

Royal North Shore Hospital; Department of Medical Oncology

St Leonards, New South Wales, Australia

Sydney Adventist Hospital; Clinical Trial Unit

Sydney, New South Wales, Australia

Royal Brisbane Hospital

Brisbane, Queensland, Australia

Rockhampton Hospital

Rockhampton, Queensland, Australia

The Townsville Hospital; Townsville Cancer Centre

Townsville, Queensland, Australia

Lyell McEwin Hospital; Oncology Clinical Trials, Chemotherapy Day Unit

Elizabeth Vale, South Australia, Australia

Calvary North Adelaide; North Adeliade Oncology Centre

North Adelaide, South Australia, Australia

Launceston General Hospital

Launceston, Tasmania, Australia

Austin Hospital; Medical Oncology

Heidelberg, Victoria, Australia

Sunshine Hospital; Oncology Research

St Albans, Victoria, Australia

St John of God Murdoch Hospital; Oncology West

Murdoch, Western Australia, Australia

St John of God Hospital; Bendat Cancer Centre

Subiaco, Western Australia, Australia

Countries

Australia

References

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.

Reference Type: DERIVED

PMID: 32142532 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 23497305 (View on PubMed)

Other Identifiers

ML25753

Identifier Type: -

Identifier Source: org_study_id