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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT01588990




Registration number
NCT01588990
Ethics application status
Date submitted
27/04/2012
Date registered
1/05/2012
Date last updated
22/01/2019

Titles & IDs
Public title
A Translational Study of Bevacizumab in Participants With Metastatic Colorectal Cancer
Scientific title
An Australian Translational Study to Evaluate the Prognostic Role of Inflammatory Markers in Patients With Metastatic Colorectal Cancer Treated With Bevacizumab (Avastin™)
Secondary ID [1] 0 0
ML25753
Universal Trial Number (UTN)
Trial acronym
ASCENT
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Colorectal Neoplasms 0 0
Condition category
Condition code
Cancer 0 0 0 0
Bowel - Back passage (rectum) or large bowel (colon)

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Oxaliplatin
Treatment: Drugs - Capecitabine
Treatment: Drugs - Bevacizumab
Treatment: Drugs - Leucovorin
Treatment: Drugs - 5-Fluouracil
Treatment: Drugs - Irinotecan

Experimental: 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.


Treatment: Drugs: 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.

Treatment: Drugs: 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.

Treatment: Drugs: 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).

Treatment: Drugs: 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).

Treatment: Drugs: 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).

Treatment: Drugs: Irinotecan
Participants will receive irinotecan 180 mg/m\^2 IV on Day 1 every 2 weeks during Phase B treatment.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Association Between Neutrophil to Lymphocyte Ratio (NLR) [NLR =5 Versus NLR >5] and Progression-Free Survival (PFS) as Assessed by Hazard Ratio
Timepoint [1] 0 0
Baseline up to disease progression, death or end of study (up to 4 years)
Secondary outcome [1] 0 0
PFS Until First Disease Progression as Assessed by the Investigator Based on Routine Clinical Practice: Phase A
Timepoint [1] 0 0
Baseline up to first disease progression, death or end of study (up to 4 years)
Secondary outcome [2] 0 0
PFS Until Second Disease Progression as Assessed by the Investigator Based on Routine Clinical Practice: Phase B
Timepoint [2] 0 0
From the start of Phase B treatment to disease progression, death or end of study (up to 4 years)
Secondary outcome [3] 0 0
Time to Failure of Strategy (TFS): Overall
Timepoint [3] 0 0
Baseline up to disease progression, death or end of study (up to 4 years)
Secondary outcome [4] 0 0
Duration of Disease Control (DDC) as Assessed by the Investigator Based on Routine Clinical Practice: Overall
Timepoint [4] 0 0
Baseline up to disease progression, death or end of study (up to 4 years)
Secondary outcome [5] 0 0
Overall Survival (OS) From the Start of Treatment to Study Completion: Overall
Timepoint [5] 0 0
Baseline until death or end of study (up to 4 years)
Secondary outcome [6] 0 0
Survival Beyond First Disease Progression: Overall
Timepoint [6] 0 0
Baseline until death or end of study (up to 4 years)
Secondary outcome [7] 0 0
OS: Phase B
Timepoint [7] 0 0
From the start of Phase B treatment death or end of study (up to 4 years)
Secondary outcome [8] 0 0
Percentage of Participants With Confirmed Complete or Partial Response as Assessed by the Investigator Based on Routine Clinical Practice: Phase A
Timepoint [8] 0 0
Baseline up to disease progression, death or end of study (up to 4 years)
Secondary outcome [9] 0 0
Percentage of Participants With Confirmed Complete or Partial Response as Assessed by the Investigator Based on Routine Clinical Practice: Phase B
Timepoint [9] 0 0
From the start of Phase B treatment to disease progression, death or end of study (up to 4 years)
Secondary outcome [10] 0 0
Percentage of Participants With Confirmed Complete or Partial Response as Assessed by the Investigator Based on Routine Clinical Practice: Overall
Timepoint [10] 0 0
Baseline up to disease progression, death or end of study (up to 4 years)
Secondary outcome [11] 0 0
Percentage of Participants Who Underwent Liver Resection: Overall
Timepoint [11] 0 0
Baseline up to disease progression, death or end of study (up to 4 years)
Secondary outcome [12] 0 0
Association Between NLR (NLR =5 Versus NLR >5) and OS as Assessed by Hazard Ratio
Timepoint [12] 0 0
Baseline up to disease progression, death or end of study (up to 4 years)
Secondary outcome [13] 0 0
Association Between NLR Normalization (First NLR Post-Baseline =5 Versus NLR >5) and PFS as Assessed by Hazard Ratio
Timepoint [13] 0 0
Baseline up to disease progression, death or end of study (up to 4 years)
Secondary outcome [14] 0 0
Association Between Longitudinal NLR (Longitudinal NLR =5 Versus NLR >5) and PFS as Assessed by Hazard Ratio
Timepoint [14] 0 0
Baseline up to disease progression, death or end of study (up to 4 years)
Secondary outcome [15] 0 0
Association Between Longitudinal NLR (Longitudinal NLR =5 Versus NLR >5) and OS as Assessed by Hazard Ratio
Timepoint [15] 0 0
Baseline up to death or end of study (up to 4 years)
Secondary outcome [16] 0 0
European Quality of Life 5-Dimension (EuroQol-5D) Utility Score: Phase A
Timepoint [16] 0 0
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]
Secondary outcome [17] 0 0
EuroQol-5D Utility Score: Phase B
Timepoint [17] 0 0
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]
Secondary outcome [18] 0 0
Assessment of Quality of Life - Eight Dimensions (AQoL-8D) Global Utility Score: Phase A
Timepoint [18] 0 0
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]
Secondary outcome [19] 0 0
AQoL-8D Global Utility Score: Phase B
Timepoint [19] 0 0
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]
Secondary outcome [20] 0 0
Functional Assessment of Cancer Therapy-Colorectal (FACT-C) Score: Phase A
Timepoint [20] 0 0
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]
Secondary outcome [21] 0 0
FACT-C Score: Phase B
Timepoint [21] 0 0
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]

Eligibility
Key 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
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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

Study design
Purpose of the study
Treatment
Allocation to intervention
Not applicable
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 4
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
26/06/2012
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
30/09/2016
Sample size
Target
Accrual to date
Final
128
Recruitment in Australia
Recruitment state(s)
ACT,NSW,QLD,SA,TAS,VIC,WA
Recruitment hospital [1] 0 0
Canberra Hospital - Garran
Recruitment hospital [2] 0 0
Macarthur Cancer Therapy Centre - Campbelltown
Recruitment hospital [3] 0 0
Chris O'Brien Lifehouse - Camperdown
Recruitment hospital [4] 0 0
St Vincent'S Hospital; Clinical Oncology - Darlinghurst
Recruitment hospital [5] 0 0
Mid North Coast Cancer Institute - Port Macquarie
Recruitment hospital [6] 0 0
Royal North Shore Hospital; Department of Medical Oncology - St Leonards
Recruitment hospital [7] 0 0
Sydney Adventist Hospital; Clinical Trial Unit - Sydney
Recruitment hospital [8] 0 0
Royal Brisbane Hospital - Brisbane
Recruitment hospital [9] 0 0
Rockhampton Hospital - Rockhampton
Recruitment hospital [10] 0 0
The Townsville Hospital; Townsville Cancer Centre - Townsville
Recruitment hospital [11] 0 0
Lyell McEwin Hospital; Oncology Clinical Trials, Chemotherapy Day Unit - Elizabeth Vale
Recruitment hospital [12] 0 0
Calvary North Adelaide; North Adeliade Oncology Centre - North Adelaide
Recruitment hospital [13] 0 0
Launceston General Hospital - Launceston
Recruitment hospital [14] 0 0
Austin Hospital; Medical Oncology - Heidelberg
Recruitment hospital [15] 0 0
Sunshine Hospital; Oncology Research - St Albans
Recruitment hospital [16] 0 0
St John of God Murdoch Hospital; Oncology West - Murdoch
Recruitment hospital [17] 0 0
St John of God Hospital; Bendat Cancer Centre - Subiaco
Recruitment postcode(s) [1] 0 0
2605 - Garran
Recruitment postcode(s) [2] 0 0
2560 - Campbelltown
Recruitment postcode(s) [3] 0 0
2050 - Camperdown
Recruitment postcode(s) [4] 0 0
2010 - Darlinghurst
Recruitment postcode(s) [5] 0 0
2444 - Port Macquarie
Recruitment postcode(s) [6] 0 0
2065 - St Leonards
Recruitment postcode(s) [7] 0 0
2076 - Sydney
Recruitment postcode(s) [8] 0 0
4029 - Brisbane
Recruitment postcode(s) [9] 0 0
4700 - Rockhampton
Recruitment postcode(s) [10] 0 0
4812 - Townsville
Recruitment postcode(s) [11] 0 0
5112 - Elizabeth Vale
Recruitment postcode(s) [12] 0 0
5006 - North Adelaide
Recruitment postcode(s) [13] 0 0
7250 - Launceston
Recruitment postcode(s) [14] 0 0
3084 - Heidelberg
Recruitment postcode(s) [15] 0 0
- St Albans
Recruitment postcode(s) [16] 0 0
6150 - Murdoch
Recruitment postcode(s) [17] 0 0
6008 - Subiaco

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Hoffmann-La Roche
Address
Country

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/study/NCT01588990
Trial related presentations / publications
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.
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.
Public notes

Contacts
Principal investigator
Name 0 0
Clinical Trials
Address 0 0
Hoffmann-La Roche
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT01588990