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

Primary Purpose

Colorectal Neoplasms

Status
Completed
Phase
Phase 4
Locations
Australia
Study Type
Interventional
Intervention
Oxaliplatin
Capecitabine
Bevacizumab
Leucovorin
5-Fluouracil
Irinotecan
Sponsored by
Hoffmann-La Roche
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Colorectal Neoplasms

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept 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

Sites / Locations

  • Canberra Hospital
  • Macarthur Cancer Therapy Centre
  • Chris O'Brien Lifehouse
  • St Vincent'S Hospital; Clinical Oncology
  • Mid North Coast Cancer Institute
  • Royal North Shore Hospital; Department of Medical Oncology
  • Sydney Adventist Hospital; Clinical Trial Unit
  • Royal Brisbane Hospital
  • Rockhampton Hospital
  • The Townsville Hospital; Townsville Cancer Centre
  • Lyell McEwin Hospital; Oncology Clinical Trials, Chemotherapy Day Unit
  • Calvary North Adelaide; North Adeliade Oncology Centre
  • Launceston General Hospital
  • Austin Hospital; Medical Oncology
  • Sunshine Hospital; Oncology Research
  • St John of God Murdoch Hospital; Oncology West
  • St John of God Hospital; Bendat Cancer Centre

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Bevacizumab: Phase A and Phase B

Arm 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.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
Percentage of Participants Who Underwent Liver Resection: Overall
The results include percentage of participants who underwent potentially curative liver resection.
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.
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.
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.
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.
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.
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.
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).
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).
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.
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.

Full Information

First Posted
April 27, 2012
Last Updated
August 17, 2018
Sponsor
Hoffmann-La Roche
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1. Study Identification

Unique Protocol Identification Number
NCT01588990
Brief Title
A Translational Study of Bevacizumab in Participants With Metastatic Colorectal Cancer
Acronym
ASCENT
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

2. Study Status

Record Verification Date
August 2018
Overall Recruitment Status
Completed
Study Start Date
June 26, 2012 (Actual)
Primary Completion Date
September 15, 2016 (Actual)
Study Completion Date
September 30, 2016 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Hoffmann-La Roche

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Colorectal Neoplasms

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
128 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Bevacizumab: Phase A and Phase B
Arm Type
Experimental
Arm 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.
Intervention Type
Drug
Intervention Name(s)
Oxaliplatin
Intervention Description
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
Intervention Name(s)
Capecitabine
Intervention Description
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
Intervention Name(s)
Bevacizumab
Other Intervention Name(s)
Avastin, RO4876646
Intervention Description
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
Intervention Name(s)
Leucovorin
Intervention Description
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
Intervention Name(s)
5-Fluouracil
Intervention Description
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
Intervention Name(s)
Irinotecan
Intervention Description
Participants will receive irinotecan 180 mg/m^2 IV on Day 1 every 2 weeks during Phase B treatment.
Primary Outcome Measure Information:
Title
Association Between Neutrophil to Lymphocyte Ratio (NLR) [NLR ≤5 Versus NLR >5] and Progression-Free Survival (PFS) as Assessed by Hazard Ratio
Description
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.
Time Frame
Baseline up to disease progression, death or end of study (up to 4 years)
Secondary Outcome Measure Information:
Title
PFS Until First Disease Progression as Assessed by the Investigator Based on Routine Clinical Practice: Phase A
Description
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.
Time Frame
Baseline up to first disease progression, death or end of study (up to 4 years)
Title
PFS Until Second Disease Progression as Assessed by the Investigator Based on Routine Clinical Practice: Phase B
Description
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.
Time Frame
From the start of Phase B treatment to disease progression, death or end of study (up to 4 years)
Title
Time to Failure of Strategy (TFS): Overall
Description
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.
Time Frame
Baseline up to disease progression, death or end of study (up to 4 years)
Title
Duration of Disease Control (DDC) as Assessed by the Investigator Based on Routine Clinical Practice: Overall
Description
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.
Time Frame
Baseline up to disease progression, death or end of study (up to 4 years)
Title
Overall Survival (OS) From the Start of Treatment to Study Completion: Overall
Description
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.
Time Frame
Baseline until death or end of study (up to 4 years)
Title
Survival Beyond First Disease Progression: Overall
Description
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.
Time Frame
Baseline until death or end of study (up to 4 years)
Title
OS: Phase B
Description
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.
Time Frame
From the start of Phase B treatment death or end of study (up to 4 years)
Title
Percentage of Participants With Confirmed Complete or Partial Response as Assessed by the Investigator Based on Routine Clinical Practice: Phase A
Description
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.
Time Frame
Baseline up to disease progression, death or end of study (up to 4 years)
Title
Percentage of Participants With Confirmed Complete or Partial Response as Assessed by the Investigator Based on Routine Clinical Practice: Phase B
Description
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.
Time Frame
From the start of Phase B treatment to disease progression, death or end of study (up to 4 years)
Title
Percentage of Participants With Confirmed Complete or Partial Response as Assessed by the Investigator Based on Routine Clinical Practice: Overall
Description
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.
Time Frame
Baseline up to disease progression, death or end of study (up to 4 years)
Title
Percentage of Participants Who Underwent Liver Resection: Overall
Description
The results include percentage of participants who underwent potentially curative liver resection.
Time Frame
Baseline up to disease progression, death or end of study (up to 4 years)
Title
Association Between NLR (NLR ≤5 Versus NLR >5) and OS as Assessed by Hazard Ratio
Description
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.
Time Frame
Baseline up to disease progression, death or end of study (up to 4 years)
Title
Association Between NLR Normalization (First NLR Post-Baseline ≤5 Versus NLR >5) and PFS as Assessed by Hazard Ratio
Description
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.
Time Frame
Baseline up to disease progression, death or end of study (up to 4 years)
Title
Association Between Longitudinal NLR (Longitudinal NLR ≤5 Versus NLR >5) and PFS as Assessed by Hazard Ratio
Description
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.
Time Frame
Baseline up to disease progression, death or end of study (up to 4 years)
Title
Association Between Longitudinal NLR (Longitudinal NLR ≤5 Versus NLR >5) and OS as Assessed by Hazard Ratio
Description
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.
Time Frame
Baseline up to death or end of study (up to 4 years)
Title
European Quality of Life 5-Dimension (EuroQol-5D) Utility Score: Phase A
Description
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.
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]
Title
EuroQol-5D Utility Score: Phase B
Description
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.
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]
Title
Assessment of Quality of Life - Eight Dimensions (AQoL-8D) Global Utility Score: Phase A
Description
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).
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]
Title
AQoL-8D Global Utility Score: Phase B
Description
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).
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]
Title
Functional Assessment of Cancer Therapy-Colorectal (FACT-C) Score: Phase A
Description
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.
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]
Title
FACT-C Score: Phase B
Description
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.
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]

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Clinical Trials
Organizational Affiliation
Hoffmann-La Roche
Official's Role
Study Director
Facility Information:
Facility Name
Canberra Hospital
City
Garran
State/Province
Australian Capital Territory
ZIP/Postal Code
2605
Country
Australia
Facility Name
Macarthur Cancer Therapy Centre
City
Campbelltown
State/Province
New South Wales
ZIP/Postal Code
2560
Country
Australia
Facility Name
Chris O'Brien Lifehouse
City
Camperdown
State/Province
New South Wales
ZIP/Postal Code
2050
Country
Australia
Facility Name
St Vincent'S Hospital; Clinical Oncology
City
Darlinghurst
State/Province
New South Wales
ZIP/Postal Code
2010
Country
Australia
Facility Name
Mid North Coast Cancer Institute
City
Port Macquarie
State/Province
New South Wales
ZIP/Postal Code
2444
Country
Australia
Facility Name
Royal North Shore Hospital; Department of Medical Oncology
City
St Leonards
State/Province
New South Wales
ZIP/Postal Code
2065
Country
Australia
Facility Name
Sydney Adventist Hospital; Clinical Trial Unit
City
Sydney
State/Province
New South Wales
ZIP/Postal Code
2076
Country
Australia
Facility Name
Royal Brisbane Hospital
City
Brisbane
State/Province
Queensland
ZIP/Postal Code
4029
Country
Australia
Facility Name
Rockhampton Hospital
City
Rockhampton
State/Province
Queensland
ZIP/Postal Code
4700
Country
Australia
Facility Name
The Townsville Hospital; Townsville Cancer Centre
City
Townsville
State/Province
Queensland
ZIP/Postal Code
4812
Country
Australia
Facility Name
Lyell McEwin Hospital; Oncology Clinical Trials, Chemotherapy Day Unit
City
Elizabeth Vale
State/Province
South Australia
ZIP/Postal Code
5112
Country
Australia
Facility Name
Calvary North Adelaide; North Adeliade Oncology Centre
City
North Adelaide
State/Province
South Australia
ZIP/Postal Code
5006
Country
Australia
Facility Name
Launceston General Hospital
City
Launceston
State/Province
Tasmania
ZIP/Postal Code
7250
Country
Australia
Facility Name
Austin Hospital; Medical Oncology
City
Heidelberg
State/Province
Victoria
ZIP/Postal Code
3084
Country
Australia
Facility Name
Sunshine Hospital; Oncology Research
City
St Albans
State/Province
Victoria
Country
Australia
Facility Name
St John of God Murdoch Hospital; Oncology West
City
Murdoch
State/Province
Western Australia
ZIP/Postal Code
6150
Country
Australia
Facility Name
St John of God Hospital; Bendat Cancer Centre
City
Subiaco
State/Province
Western Australia
ZIP/Postal Code
6008
Country
Australia

12. IPD Sharing Statement

Citations:
PubMed Identifier
32142532
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.
Results Reference
derived
PubMed Identifier
23497305
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.
Results Reference
derived

Learn more about this trial

A Translational Study of Bevacizumab in Participants With Metastatic Colorectal Cancer

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