Colorectal NeoplasmsPhase 4ASCENTNCT01588990
A Translational Study of Bevacizumab in Participants With Metastatic Colorectal Cancer
A Phase 4 study testing Oxaliplatin, Capecitabine and Bevacizumab in people with Colorectal Neoplasms, run by Hoffmann-La Roche at 17 sites in Australia.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Colorectal Neoplasms
- What is being tested?
- Oxaliplatin, Capecitabine and Bevacizumab
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 128 participants
- Where
- 17 sitesAustralia
- Study dates
- 26 Jun 2012to 30 Sep 2016
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 16Show fewer
- 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 locations and contacts
17 sites in 1 country.
17 sites in 1 country
Australia17 sites
Royal Brisbane Hospital
Brisbane, Queensland, 4029
Macarthur Cancer Therapy Centre
Campbelltown, New South Wales, 2560
Chris O'Brien Lifehouse
Camperdown, New South Wales, 2050
St Vincent'S Hospital; Clinical Oncology
Darlinghurst, New South Wales, 2010
Lyell McEwin Hospital; Oncology Clinical Trials, Chemotherapy Day Unit
Elizabeth Vale, South Australia, 5112
Canberra Hospital
Garran, Australian Capital Territory, 2605
Austin Hospital; Medical Oncology
Heidelberg, Victoria, 3084
Launceston General Hospital
Launceston, Tasmania, 7250
St John of God Murdoch Hospital; Oncology West
Murdoch, Western Australia, 6150
Calvary North Adelaide; North Adeliade Oncology Centre
North Adelaide, South Australia, 5006
Mid North Coast Cancer Institute
Port Macquarie, New South Wales, 2444
Rockhampton Hospital
Rockhampton, Queensland, 4700
Sunshine Hospital; Oncology Research
St Albans, Victoria
Royal North Shore Hospital; Department of Medical Oncology
St Leonards, New South Wales, 2065
St John of God Hospital; Bendat Cancer Centre
Subiaco, Western Australia, 6008
Sydney Adventist Hospital; Clinical Trial Unit
Sydney, New South Wales, 2076
The Townsville Hospital; Townsville Cancer Centre
Townsville, Queensland, 4812
About this study
Official title: An Australian Translational Study to Evaluate the Prognostic Role of Inflammatory Markers in Patients With Metastatic Colorectal Cancer Treated With Bevacizumab (Avastin™)
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
- Being tested
- Oxaliplatin, Capecitabine, Bevacizumab, Leucovorin, 5-Fluouracil
- Medical subject headings
- Colorectal Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
OxaliplatinDrug
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.
CapecitabineDrug
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.
BevacizumabDrug
Also called Avastin, RO4876646
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).
LeucovorinDrug
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-FluouracilDrug
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).
IrinotecanDrug
Participants will receive irinotecan 180 mg/m^2 IV on Day 1 every 2 weeks during Phase B treatment.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Drug: Oxaliplatin; Drug: Capecitabine; Drug: Bevacizumab; Drug: Leucovorin; Drug: 5-Fluouracil; Drug: Irinotecan |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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
PFS until first progression 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 (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. Kaplan-Meier methodology was used to estimate PFS.
Measured: 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
PFS in Phase B (PFS-B) was defined as the time from the start of Phase B treatment to documentation of second disease progression or death from any cause, whichever occurred first. Disease progression was determined according to standard practice based on radiological, biochemical (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. Kaplan-Meier methodology was used to estimate PFS.
Measured: 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
TFS was defined as time from the start of initial treatment to documentation of first disease progression without entering Phase B, or second disease progression having entered Phase B. Disease progression was determined according to standard practice based on radiological, biochemical (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. Kaplan-Meier methodology was used to estimate TFS.
Measured: 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
DDC was defined as PFS + PFS-B. In cases where a participant did not enter Phase B, then DDC was defined as PFS. PFS was defined as time from start of initial treatment to documentation of first disease progression or death from any cause, whichever occurred first. PFS-B was time from start of Phase B treatment to documentation of second disease progression or death from any cause, whichever occurred first. Disease progression was determined according to standard practice based on radiological, biochemical (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, 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. Kaplan-Meier methodology was used to estimate DDC.
Measured: 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
OS was defined as the time from the start of initial treatment to the date of death, regardless of the cause of death. Kaplan-Meier methodology was used to estimate OS.
Measured: Baseline until death or end of study (up to 4 years)
Survival Beyond First Disease Progression: Overall
Survival beyond first progression was defined as the time from the date of first disease progression to death due to any cause. Disease progression was determined according to standard practice based on radiological, biochemical (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. Kaplan-Meier methodology was used to estimate survival beyond first disease progression.
Measured: Baseline until death or end of study (up to 4 years)
OS: Phase B
Overall Survival in Phase B was defined as the time from the start of treatment in Phase B to death due to any cause. Kaplan-Meier methodology was used to estimate OS.
Measured: From the start of Phase B treatment death or end of study (up to 4 years)
Percentage of Participants With Confirmed Complete or Partial Response as Assessed by the Investigator Based on Routine Clinical Practice: Phase A
Percentage of participants with best overall response of confirmed complete response or partial response based on the investigator assessment of the response as per routine clinical practice was reported. The confirmation of response must be no less than 4 weeks after initial assessment.
Measured: Baseline up to disease progression, death or end of study (up to 4 years)
Percentage of Participants With Confirmed Complete or Partial Response as Assessed by the Investigator Based on Routine Clinical Practice: Phase B
Percentage of participants with best overall response of confirmed complete response or partial response based on the investigator assessment of the response as per routine clinical practice was reported. The confirmation of response must be no less than 4 weeks after initial assessment.
Measured: From the start of Phase B treatment to disease progression, death or end of study (up to 4 years)
Percentage of Participants With Confirmed Complete or Partial Response as Assessed by the Investigator Based on Routine Clinical Practice: Overall
Percentage of participants with best overall response of confirmed complete response or partial response based on the investigator assessment of the response as per routine clinical practice was reported. The confirmation of response must be no less than 4 weeks after initial assessment.
Measured: Baseline up to disease progression, death or end of study (up to 4 years)
Percentage of Participants Who Underwent Liver Resection: Overall
The results include percentage of participants who underwent potentially curative liver resection.
Measured: Baseline up to disease progression, death or end of study (up to 4 years)
Association Between NLR (NLR ≤5 Versus NLR >5) and OS as Assessed by Hazard Ratio
NLR was calculated from the laboratory values as the ratio of Neutrophils to Lymphocytes. OS was defined as the time from the start of initial treatment to the date of death, regardless of the cause of death. The association between NLR (NLR ≤ 5 vs > 5) and OS was reported as hazard ratio.
Measured: Baseline up to disease progression, death or end of study (up to 4 years)
Association Between NLR Normalization (First NLR Post-Baseline ≤5 Versus NLR >5) and PFS as Assessed by Hazard Ratio
NLR was calculated from laboratory values as ratio of Neutrophils to Lymphocytes. NLR normalization was assessed by adding first post-baseline measurement of NLR to the primary model. This is equivalent to testing whether first change in NLR is significantly associated with outcome. PFS was defined as time from start of initial treatment to documentation of first disease progression or death from any cause. Disease progression was determined according to standard practice based on radiological, biochemical (CEA) or clinical factors. Determination of disease progression was defined as: an unequivocal and clinically meaningful increase in size of known tumors, appearance of ≥1 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 normalization (first NLR post-baseline ≤5 vs >5) and PFS was reported as hazard ratio.
Measured: Baseline up to disease progression, death or end of study (up to 4 years)
Association Between Longitudinal NLR (Longitudinal NLR ≤5 Versus NLR >5) and PFS as Assessed by Hazard Ratio
NLR was calculated from the laboratory values as the ratio of Neutrophils to Lymphocytes. Longitudinal NLR was assessed by treating the NLR measurements taken over the time-course of treatment as a time-dependent covariate. PFS was defined as 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 (CEA) or clinical factors. Determination of disease progression was to be unequivocal and was defined as: an unequivocal and clinically meaningful increase in size of known tumors, 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 longitudinal NLR (longitudinal NLR ≤5 vs N>5) and PFS was reported as hazard ratio.
Measured: Baseline up to disease progression, death or end of study (up to 4 years)
Association Between Longitudinal NLR (Longitudinal NLR ≤5 Versus NLR >5) and OS as Assessed by Hazard Ratio
NLR was calculated from the laboratory values as the ratio of Neutrophils to Lymphocytes. Longitudinal NLR was assessed by treating the NLR measurements taken over the time-course of treatment as a time-dependent covariate. OS was defined as the time from the start of initial treatment to the date of death, regardless of the cause of death. The association between longitudinal NLR (longitudinal NLR ≤5 vs NLR >5) and OS was reported as hazard ratio.
Measured: Baseline up to death or end of study (up to 4 years)
European Quality of Life 5-Dimension (EuroQol-5D) Utility Score: Phase A
EQ-5D is a standardized generic preference based health related quality of life instrument. It records how one's health is "today" and consists of a descriptive system. The descriptive system is comprised of 5 dimensions: mobility, self-care, usual activities, pain/discomfort, anxiety/depression. Each dimension on the EQ-5D involves a 3-point response scale which indicates the level of impairment (level 1 = no problem; level 2 = some or moderate problem[s] and level 3 = unable, or extreme problems). Level of problem reported in each EQ-5D dimension determines a unique health state which is converted into a weighted health state index by applying scores from EQ-5D preference weights elicited from general population samples. This generates a unique description of the subjects' health status, which is valued between 0 (representing death) and 1 (representing perfect health). Higher the score, the better the quality of life.
Measured: 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]
EuroQol-5D Utility Score: Phase B
EQ-5D is a standardized generic preference based health related quality of life instrument. It records how one's health is "today" and consists of a descriptive system. The descriptive system is comprised of 5 dimensions: mobility, self-care, usual activities, pain/discomfort, anxiety/depression. Each dimension on the EQ-5D involves a 3-point response scale which indicates the level of impairment (level 1 = no problem; level 2 = some or moderate problem[s] and level 3 = unable, or extreme problems). Level of problem reported in each EQ-5D dimension determines a unique health state which is converted into a weighted health state index by applying scores from EQ-5D preference weights elicited from general population samples. This generates a unique description of the subjects' health status, which is valued between 0 (representing death) and 1 (representing perfect health). Higher the score, the better the quality of life.
Measured: 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]
Assessment of Quality of Life - Eight Dimensions (AQoL-8D) Global Utility Score: Phase A
AQoL-8D provides a global utility score and comprised of 35 questions from which 8 dimensions (Independent Living, Life Satisfaction, Mental Health, Coping, Relationships, Self Worth, Pain, and Senses) are derived. Each of the 8 scales is calculated based on the answers to 3 questions. Each question is given an answer dependent utility score (0 [worst] to 1 [best]) and then these scores are combined using a multiplicative model to get the normalized scale score value, each scale ranging between 0.0 (representing death) and 1.0 (representing full health).
Measured: 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]
AQoL-8D Global Utility Score: Phase B
AQoL-8D provides a global utility score and consists of 8 separately scored dimensions including Independent Living, Life Satisfaction, Mental Health, Coping, Relationships, Self Worth, Pain, and Senses. Each of the 8 scales is calculated based on the answers to 3 questions. Each question is given an answer dependent utility score (0 [worst] to 1 [best]) and then these scores are combined using a multiplicative model to get the normalized scale score value, each scale ranging between 0.0 (representing death) and 1.0 (representing full health).
Measured: 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]
Functional Assessment of Cancer Therapy-Colorectal (FACT-C) Score: Phase A
FACT-C is one part of the Functional Assessment of Chronic Illness Therapy (FACIT) Measurement System, which comprehensively assesses the health-related QoL of cancer participants and participants with other chronic illnesses. It is composed of 27 items of the general version of the FACT-C as a general core QoL measure and has a disease-specific subscale containing 9 colorectal cancer-specific items. It consists of total 36 items, summarized to 5 subscales: physical well-being (7 items), functional well-being (7 items), social/family well-being (7 items); all 3 subscales range from 0 to 28, emotional well-being (6 items) range from 0 to 24, colorectal cancer subscale (9 items) range from 0 to 36; higher subscale score=better QoL. All single-item measures range from 0='Not at all' to 4='Very much'. Total possible score range: 0 to 144. High scale score represents a better QoL.
Measured: 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]
FACT-C Score: Phase B
FACT-C is one part of the FACIT Measurement System, which comprehensively assesses the health-related QoL of cancer participants and participants with other chronic illnesses. It is composed of 27 items of the general version of the FACT-C as a general core QoL measure and has a disease-specific subscale containing 9 colorectal cancer-specific items. It consists of total 36 items, summarized to 5 subscales: physical well-being (7 items), functional well-being (7 items), social/family well-being (7 items); all 3 subscales range from 0 to 28, emotional well-being (6 items) range from 0 to 24, colorectal cancer subscale (9 items) range from 0 to 36; higher subscale score=better QoL. All single-item measures range from 0='Not at all' to 4='Very much'. Total possible score range: 0 to 144. High scale score represents a better QoL.
Measured: 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]
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 May 2012 (estimated)
- Study start26 Jun 2012
- Primary completion15 Sep 2016
- Study completion30 Sep 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Colorectal NeoplasmsStudies of the same condition, open and under way.
- More trials run by Hoffmann-La RocheThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 128 participants (actual)
Sponsor and investigators
- Lead sponsor
- Hoffmann-La Roche
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Clinical Trials, Study director, Hoffmann-La Roche
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01588990
- Sponsor's protocol ID
- ML25753
- Acronym
- ASCENT
- Status last verified
- Aug 2018
- First submitted
- 27 Apr 2012
- Last updated
- 22 Jan 2019
- Results posted
- Yes, on ClinicalTrials.gov
- FDA-regulated drug
- No
- FDA-regulated device
- No
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.
PubMed 32142532Clarke 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.
PubMed 23497305
Study at a glance
From the registry record, last updated by the sponsor on 22 Jan 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Australian Translational Study to Evaluate the Prognostic Role of Inflammatory Markers in Patients With Metastatic Colorectal Cancer Treated With Bevacizumab (Avastin™)
- ClinicalTrials.gov ID
- NCT01588990
- Acronym / sponsor ID
- ASCENT / ML25753
- Conditions
- Colorectal Neoplasms
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 128 participants (actual)
- Lead sponsor
- Hoffmann-La RocheIndustry (pharma, biotech, devices)
- Study start
- 26 Jun 2012 (actual)
- Primary completion
- 15 Sep 2016 (actual)
- Study completion
- 30 Sep 2016 (actual)
- First posted
- 1 May 2012 (estimated)
- Results
- Posted 22 Jan 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Bevacizumab: Phase A and Phase B | Experimental | Drug: Oxaliplatin, Drug: Capecitabine, Drug: Bevacizumab, Drug: Leucovorin, Drug: 5-Fluouracil, Drug: IrinotecanThe 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- 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
Key exclusion criteria (16 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| OxaliplatinParticipants 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. | Drug | Bevacizumab: Phase A and Phase B |
| CapecitabineParticipants will receive capecitabine 1000 mg/m^2 per oral (PO) twice daily on Days 1-14 of 3 weeks cycle during Phase A treatment. | Drug | Bevacizumab: Phase A and Phase B |
| BevacizumabAlso: Avastin, RO4876646Participants 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). | Drug | Bevacizumab: Phase A and Phase B |
| LeucovorinParticipants 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). | Drug | Bevacizumab: Phase A and Phase B |
| 5-FluouracilParticipants 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). | Drug | Bevacizumab: Phase A and Phase B |
| IrinotecanParticipants will receive irinotecan 180 mg/m^2 IV on Day 1 every 2 weeks during Phase B treatment. | Drug | Bevacizumab: Phase A and Phase B |
Primary outcome
Association Between Neutrophil to Lymphocyte Ratio (NLR) [NLR ≤5 Versus NLR >5] and Progression-Free Survival (PFS) as Assessed by Hazard Ratio
Time frame: Baseline up to disease progression, death or end of study (up to 4 years)
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.
21 secondary outcomes
PFS Until First Disease Progression as Assessed by the Investigator Based on Routine Clinical Practice: Phase A
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: Baseline until death or end of study (up to 4 years)
Survival Beyond First Disease Progression: Overall
Time frame: Baseline until death or end of study (up to 4 years)
OS: Phase B
Time frame: From the start of Phase B treatment death or end of study (up to 4 years)
Percentage of Participants With Confirmed Complete or Partial Response as Assessed by the Investigator Based on Routine Clinical Practice: Phase A
Time frame: Baseline up to disease progression, death or end of study (up to 4 years)
Percentage of Participants With Confirmed Complete or Partial Response as Assessed by the Investigator Based on Routine Clinical Practice: Phase B
Time frame: From the start of Phase B treatment to disease progression, death or end of study (up to 4 years)
Percentage of Participants With Confirmed Complete or Partial Response as Assessed by the Investigator Based on Routine Clinical Practice: Overall
Time frame: Baseline up to disease progression, death or end of study (up to 4 years)
Percentage of Participants Who Underwent Liver Resection: Overall
Time frame: Baseline up to disease progression, death or end of study (up to 4 years)
Association Between NLR (NLR ≤5 Versus NLR >5) and OS as Assessed by Hazard Ratio
Time frame: Baseline up to disease progression, death or end of study (up to 4 years)
Association Between NLR Normalization (First NLR Post-Baseline ≤5 Versus NLR >5) and PFS as Assessed by Hazard Ratio
Time frame: Baseline up to disease progression, death or end of study (up to 4 years)
Association Between Longitudinal NLR (Longitudinal NLR ≤5 Versus NLR >5) and PFS as Assessed by Hazard Ratio
Time frame: Baseline up to disease progression, death or end of study (up to 4 years)
Association Between Longitudinal NLR (Longitudinal NLR ≤5 Versus NLR >5) and OS as Assessed by Hazard Ratio
Time frame: Baseline up to death or end of study (up to 4 years)
European Quality of Life 5-Dimension (EuroQol-5D) Utility Score: Phase A
Time frame: 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]
EuroQol-5D Utility Score: Phase B
Time frame: 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]
Assessment of Quality of Life - Eight Dimensions (AQoL-8D) Global Utility Score: Phase A
Time frame: 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]
AQoL-8D Global Utility Score: Phase B
Time frame: 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]
Functional Assessment of Cancer Therapy-Colorectal (FACT-C) Score: Phase A
Time frame: 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]
FACT-C Score: Phase B
Time frame: 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]
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Jan 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 32142532Clarke 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.
- Derived from this study: PubMed 23497305Clarke 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Clinical Trials study director
Hoffmann-La Roche
17 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Oxaliplatin, Capecitabine and Bevacizumab in people with Colorectal Neoplasms, run by Hoffmann-La Roche at 17 sites in Australia.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 22 Jan 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 17 sites in Australia. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 22 Jan 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Association Between Neutrophil to Lymphocyte Ratio (NLR) [NLR ≤5 Versus NLR >5] and Progression-Free Survival (PFS) as Assessed by Hazard Ratio (time frame: Baseline up to disease progression, death or end of study (up to 4 years)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01588990, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Jan 2019.