Clinical trial NCT01588990: A Translational Study of Bevacizumab in Participants With Metastatic Colorectal Cancer
Official title: An Australian Translational Study to Evaluate the Prognostic Role of Inflammatory Markers in Patients With Metastatic Colorectal Cancer Treated With Bevacizumab (Avastin™)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Colorectal Neoplasms
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
First posted: 2012-05-01
Enrollment: 128
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


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

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

Primary outcomes:
measure: Association Between Neutrophil to Lymphocyte Ratio (NLR) [NLR ≤5 Versus NLR >5] and Progression-Free Survival (PFS) as Assessed by Hazard Ratio
timeFrame: Baseline up to disease progression, death or end of study (up to 4 years)
Secondary outcomes:
measure: PFS Until First Disease Progression as Assessed by the Investigator Based on Routine Clinical Practice: Phase A
timeFrame: Baseline up to first disease progression, death or end of study (up to 4 years)
measure: PFS Until Second Disease Progression as Assessed by the Investigator Based on Routine Clinical Practice: Phase B
timeFrame: From the start of Phase B treatment to disease progression, death or end of study (up to 4 years)
measure: Time to Failure of Strategy (TFS): Overall
timeFrame: Baseline up to disease progression, death or end of study (up to 4 years)
measure: Duration of Disease Control (DDC) as Assessed by the Investigator Based on Routine Clinical Practice: Overall
timeFrame: Baseline up to disease progression, death or end of study (up to 4 years)
measure: Overall Survival (OS) From the Start of Treatment to Study Completion: Overall
timeFrame: Baseline until death or end of study (up to 4 years)
measure: Survival Beyond First Disease Progression: Overall
timeFrame: Baseline until death or end of study (up to 4 years)
measure: OS: Phase B
timeFrame: From the start of Phase B treatment death or end of study (up to 4 years)
measure: Percentage of Participants With Confirmed Complete or Partial Response as Assessed by the Investigator Based on Routine Clinical Practice: Phase A
timeFrame: Baseline up to disease progression, death or end of study (up to 4 years)
measure: Percentage of Participants With Confirmed Complete or Partial Response as Assessed by the Investigator Based on Routine Clinical Practice: Phase B
timeFrame: From the start of Phase B treatment to disease progression, death or end of study (up to 4 years)
measure: Percentage of Participants With Confirmed Complete or Partial Response as Assessed by the Investigator Based on Routine Clinical Practice: Overall
timeFrame: Baseline up to disease progression, death or end of study (up to 4 years)
measure: Percentage of Participants Who Underwent Liver Resection: Overall
timeFrame: Baseline up to disease progression, death or end of study (up to 4 years)
measure: Association Between NLR (NLR ≤5 Versus NLR >5) and OS as Assessed by Hazard Ratio
timeFrame: Baseline up to disease progression, death or end of study (up to 4 years)
measure: Association Between NLR Normalization (First NLR Post-Baseline ≤5 Versus NLR >5) and PFS as Assessed by Hazard Ratio
timeFrame: Baseline up to disease progression, death or end of study (up to 4 years)
measure: Association Between Longitudinal NLR (Longitudinal NLR ≤5 Versus NLR >5) and PFS as Assessed by Hazard Ratio
timeFrame: Baseline up to disease progression, death or end of study (up to 4 years)
measure: Association Between Longitudinal NLR (Longitudinal NLR ≤5 Versus NLR >5) and OS as Assessed by Hazard Ratio
timeFrame: Baseline up to death or end of study (up to 4 years)
measure: European Quality of Life 5-Dimension (EuroQol-5D) Utility Score: Phase A
timeFrame: Baseline, every 8-9 weeks thereafter, end of treatment (EOT) (30 days after disease progression [up to 4 years]), survival follow-up 12-weekly visits (up to 4 years) [Detailed time points are presented in the category titles]
measure: EuroQol-5D Utility Score: Phase B
timeFrame: Baseline, every 8-9 weeks thereafter, EOT (30 days after disease progression [up to 4 years]), survival follow-up 12-weekly visits (up to 4 years) [Detailed time points are presented in the category titles]
measure: Assessment of Quality of Life - Eight Dimensions (AQoL-8D) Global Utility Score: Phase A
timeFrame: Baseline, every 8-9 weeks thereafter, EOT (30 days after disease progression [up to 4 years]), survival follow-up 12-weekly visits (up to 4 years) [Detailed time points are presented in the category titles]
measure: AQoL-8D Global Utility Score: Phase B
timeFrame: Baseline, every 8-9 weeks thereafter, EOT (30 days after disease progression [up to 4 years]), survival follow-up 12-weekly visits (up to 4 years) [Detailed time points are presented in the category titles]
measure: Functional Assessment of Cancer Therapy-Colorectal (FACT-C) Score: Phase A
timeFrame: Baseline, every 8-9 weeks thereafter, EOT (30 days after disease progression [up to 4 years]), survival follow-up 12-weekly visits (up to 4 years) [Detailed time points are presented in the category titles]
measure: FACT-C Score: Phase B
timeFrame: Baseline, every 8-9 weeks thereafter, EOT (30 days after disease progression [up to 4 years]), survival follow-up 12-weekly visits (up to 4 years) [Detailed time points are presented in the category titles]
Other outcomes:
Locations:
city: Garran
country: Australia
facility: Canberra Hospital
state: Australian Capital Territory
city: Campbelltown
country: Australia
facility: Macarthur Cancer Therapy Centre
state: New South Wales
city: Camperdown
country: Australia
facility: Chris O'Brien Lifehouse
state: New South Wales
city: Darlinghurst
country: Australia
facility: St Vincent'S Hospital; Clinical Oncology
state: New South Wales
city: Port Macquarie
country: Australia
facility: Mid North Coast Cancer Institute
state: New South Wales
city: St Leonards
country: Australia
facility: Royal North Shore Hospital; Department of Medical Oncology
state: New South Wales
city: Sydney
country: Australia
facility: Sydney Adventist Hospital; Clinical Trial Unit
state: New South Wales
city: Brisbane
country: Australia
facility: Royal Brisbane Hospital
state: Queensland
city: Rockhampton
country: Australia
facility: Rockhampton Hospital
state: Queensland
city: Townsville
country: Australia
facility: The Townsville Hospital; Townsville Cancer Centre
state: Queensland
city: Elizabeth Vale
country: Australia
facility: Lyell McEwin Hospital; Oncology Clinical Trials, Chemotherapy Day Unit
state: South Australia
city: North Adelaide
country: Australia
facility: Calvary North Adelaide; North Adeliade Oncology Centre
state: South Australia
city: Launceston
country: Australia
facility: Launceston General Hospital
state: Tasmania
city: Heidelberg
country: Australia
facility: Austin Hospital; Medical Oncology
state: Victoria
city: St Albans
country: Australia
facility: Sunshine Hospital; Oncology Research
state: Victoria
city: Murdoch
country: Australia
facility: St John of God Murdoch Hospital; Oncology West
state: Western Australia
city: Subiaco
country: Australia
facility: St John of God Hospital; Bendat Cancer Centre
state: Western Australia
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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.