A Translational Study of Bevacizumab in Participants With Metastatic Colorectal Cancer (ASCENT)

Roche

Status and phase: Completed; Phase 4

Conditions: Colorectal Neoplasms

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

Study type: Interventional

Funder types: Industry

Identifiers

NCT01588990

ML25753

Details and patient eligibility

About

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.

Enrollment: 128 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Additional inclusion criteria for participants with primary tumor in situ:

• 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

Additional exclusion criteria for participants with primary tumor in situ:

• Prior endoscopic management of the current tumor
• Acute diverticulitis
• Presence of intra-abdominal abscess
• Active gastroduodenal ulcer

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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128 participants in 1 patient group

Bevacizumab: Phase A and Phase B

Experimental group

Description:

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.

Treatment:

Drug: 5-Fluouracil

Drug: Leucovorin

Drug: Irinotecan

Drug: Oxaliplatin

Drug: Capecitabine

Drug: Bevacizumab