Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12618000054213
Ethics application status
Approved
Date submitted
30/08/2017
Date registered
17/01/2018
Date last updated
17/01/2018
Type of registration
Retrospectively registered

Titles & IDs
Public title
The Sydney 1000 Bowel Cancer Study and Biobank: a 10 year observational study following the treatment pathways and outcomes of 1000 patients recently diagnosed with colorectal cancer (CRC).
Scientific title
The Sydney 1000 CRC Study and Biobank: a prospective, longitudinal, observational, multi-centre cohort study of 1000 sequential patients diagnosed with all stages of colorectal cancer to better understand disease progression, identify novel biomarkers, determine the impact of toxicity on patient quality of life and develop optimised individualised treatment pathways for future patients.
Secondary ID [1] 292740 0
Nil
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
bowel cancer 304579 0
colorectal cancer 304580 0
Condition category
Condition code
Cancer 303911 303911 0 0
Bowel - Back passage (rectum) or large bowel (colon)
Cancer 303912 303912 0 0
Bowel - Anal
Cancer 303913 303913 0 0
Bowel - Small bowel (duodenum and ileum)

Intervention/exposure
Study type
Observational
Patient registry
False
Target follow-up duration
Target follow-up type
Description of intervention(s) / exposure
Participants will be observed from the point of diagnosis, during active treatment, during short-term clinical follow-up and for up to 10 years (or until the study ends in June 2029). Data collection includes biological samples (colorectal tumour and normal tissue, blood and faecal samples), clinical management data from patient's medical records, patient-reported questionnaires (quality of life, side effects of chemotherapy, nutrition, physical activity, anxiety and depression and lifestyle), activity count levels and completion of patient-reported data on dietary intake.
Intervention code [1] 299015 0
Not applicable
Comparator / control treatment
No control group
Control group
Uncontrolled

Outcomes
Primary outcome [1] 303248 0
Identify novel tumour biomarkers.
Timepoint [1] 303248 0
1-5 years of treatment, with analysis of samples for biomarkers collected:
- Blood, faecal and Colorectal tissue collected at baseline.
- Faecal every change of therapy.
- Blood pre/post therapy (surgery, chemotherapy and radiotherapy) and every 8 weeks during therapy.
- Blood and faecal samples collected every 6 months years 1-3 and annually years 4 & 5.

Primary outcome [2] 303314 0
Impact of self-reported toxicity levels on patient quality of life.
Timepoint [2] 303314 0
Comparison of baseline scores with treatment scores for the following self assessments:
- Toxicity Score based on non-validated Northern Cancer Institute toxicity form
- validated EORTC QLQ-C30
- Sydney1000 specific CRC quality of life questionnaire with the EORTC QLQ-CR29 (module validated) embedded
- non-validated (phaseIV) EORTC QLQ CIPN20
- validated HADs questionnaire
- Sydney 1000 CRC Study specific lifestyle questionnaire (based on the 45&Up questionnaire) covering lifestyle factors such as: personal and familial health conditions and medications; general health (including weight, pain and falls history); smoking and alcohol consumption; daily occupations and activity levels (including sedentary activities),time spent outdoors and in social activities; and well-being/mood.
- physical activity levels questionnaire (adapted from the Global Physical Activity
Questionnaire).

Toxicity scores are collected on day 1 at the start of each cycle and during treatment only (not collected during follow up).

For other instruments:
Treatment: every 3 months during treatment (with the exception of the lifestyle questionnaire which is 6 monthly)
Follow-up: every 6 months during years 1-3 of follow-up and 12 monthly during years 4-10
Secondary outcome [1] 338613 0
Change of activity levels assessed by
1. Physical activity questionnaire (non-validated questionnaire developed for Sydney 1000 CRC based on the Global Physical Activity Questionnaire.
2. ActiGraph device worn for 7 consecutive day and nights.
Timepoint [1] 338613 0
Baseline, every 3 month during treatment and follow-up (every 6 months in years 4-10)
Secondary outcome [2] 339843 0
Changes in diet assessed using:
1)Cancer Council Victoria Food Frequency Questionnaire (DQESv3.2)
2.) a 24 hour recall diary (Myfood 24)
3) PG-SGA (SF) questionnaire
Timepoint [2] 339843 0
DQESv3.2 data is collected at baseline and followup (at 3 years post treatment and 10 years/end of study

The PG-SGA (SF) questionnaire and the 24 hour recall diary are both collected every 3 months during treatment and fixed points in follow-up (every 6 months for years 1-3 and every 12 months years 4-10)
3)
Secondary outcome [3] 339850 0
Change in clinical treatment pathway as assessed by comparison of clinical data of treatment delivered as compared to treatment planned (collected by accessing medical records) and Clinical Practice Guidelines (e.g. Clinical practice guidelines for the prevention, early detection and management of colorectal cancer (CRC) 3rd edition (2017)).

Clinical care data collected through accessing records of:
• Multidisciplinary team discussion outcome/decisions, treatment planned, actual treatment delivered,
• Full blood count results, blood biochemistry results, tumour marker results, tumour detection results (X-ray, CT scan, colonoscopy)
• Time between diagnosis and surgery or chemotherapy or radiotherapy or combined therapy, number of patients having surgery, chemotherapy and radiotherapy
Timepoint [3] 339850 0
Data collected at each clinical visit / tests administered during diagnosis, treatment and follow-up phases (upto 5 years post surgery) - exact timepoints will vary per individual participant according to the clinicians decision making about patients care.
Secondary outcome [4] 341868 0
Effectiveness of surgery treatment assessed by patient outcome data including:
• Type of surgery, surgical complication rates (up to 1 month), length of post-operative stay
• Number of patients have surgery in year 1 of diagnosis
• time between surgery and chemotherapy or radiotherapy,
• time between surgery and subsequent follow-up colonoscopy
• full blood count results, blood biochemistry results, tumour marker results, tumour detection results (X-ray, CT scan, colonoscopy)

Long-term patient outcomes (collected at 10 year timepoint or sooner if applicable).
• Death, cause of death,
• Long term toxicity, type of toxicity, duration of toxicity
• Tumour recurrence, tumour recurrence location, time to recurrence,

Timepoint [4] 341868 0
Collected at each clinical visit / tests administered during diagnosis, treatment and follow-up phases (upto 5 years post surgery) - exact timepoints will vary per individual participant according to the clinicians decision making about patients care.

Long-term patient outcomes collected when death occurs or at 10 year timepoint.
Secondary outcome [5] 341870 0
Effectiveness of chemotherapy treatment assessed by clinical and patient outcome data including:
• Type of chemotherapy (cytotoxic, biological, combination),
• Number of lines of therapy (defined using method in Abrams JNCI 2014)
• doses of chemotherapy given, dose modification and delays, reasons for treatment choice and dose modification/delay
• Response to chemotherapy (best response, RECIST, clinical)
• full blood count results, blood biochemistry results, tumour marker results, tumour detection results (X-ray, CT scan, colonoscopy)
• Duration of chemotherapy lines (PFS),
• Toxicity data per chemotherapy for each line of therapy
Timepoint [5] 341870 0
Collected at each clinical visit / tests administered during diagnosis, treatment and follow-up phases (upto 5 years post surgery) - exact timepoints will vary per individual participant according to the clinicians decision making about patients care.

Long-term patient outcomes collected when death occurs or at 10 year timepoint.
Secondary outcome [6] 341871 0
Effectiveness of radiotherapy treatment assessed by clinical and patient outcome data including:

• Type of radiotherapy course (short, long course), number of sessions, number of boost sessions, completion rates,
• Toxicity data per week of treatment
• Full blood count results, blood biochemistry results, tumour marker results, tumour detection results (X-ray, CT scan, colonoscopy).
Timepoint [6] 341871 0
Collected at each clinical visit / tests administered during diagnosis, treatment and follow-up phases (upto 5 years post surgery) - exact timepoints will vary per individual participant according to the clinicians decision making about patients care.

Long-term patient outcomes collected when death occurs or at 10 year timepoint.
Secondary outcome [7] 341872 0
Changes in gastrointestinal microbiome genetic diversity profile.
Timepoint [7] 341872 0
Faecal samples collected:
A) during treatment: at baseline and before each new treatment (e.g. surgery, pre-radiotherapy, pre-chemotherapy).

B) years 1 - 5 following treatment: every 6 months years 1-3 and annually years 4 & 5.

Eligibility
Key inclusion criteria
• Over the age of 18 years
• Diagnosis of colorectal cancer (any stage of cancer)
• Willingness to give written informed consent to participate in the study and to comply with the planned procedures for providing biological samples and outcome data.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
• Patients with insufficient English to complete the self-reported questionnaires
• People unavailable or unwilling to consent to ongoing follow-up.

Study design
Purpose
Screening
Duration
Longitudinal
Selection
Defined population
Timing
Prospective
Statistical methods / analysis
SAMPLE SIZE
The study will recruit 1000 participants sequentially at presentation. This will allow the cohort to be representative of the population in terms of cancer stage distribution in the community. We will recruit at least 150 patients from each of the main cancer ‘diagnoses’ or ‘stage’ (e.g. stages 1 to 4) as this will allow for analysis of secondary endpoints and hypothesis-generating follow-up research studies. Although there is no formal statistical sample size calculation, previous studies in colorectal cancer have used populations of similar sample size or less to determine predictors of survival using genetic cluster profile or immune cell profiles. The Cancer Genome Atlas project analysed the genetic profiles 276 colorectal tumours (Stage 1 n=4, Stage 2 n=103, Stage 3 n= 68, Stage 4 n=43) to predict survival without other clinical treatment covariates (Nature 2012, 487, 330–337).

DATA COLLECTION

Each centre provides information on patients not randomised into the study (overall number, reasons for exclusion).

Demographic data
• Age, sex, self-reported ethnicity, functional status (ECOG), comorbidity status (Charlson Comorbidity Score), socio-economic status (post code), weight, height, BSA, BMI
Cancer data
• pathological site (ICD-10), pathological stage (AJCC), number of tumour lesions, size of tumour lesions, histology, metastasis locations, lymphatic or venous invasion, key mutation status (MSI, KRAS, BRAF, PI3KCA), age at diagnosis

Treatment plan data
• Discussion at MDT, treatment plan details, number of patients having surgery, chemotherapy and radiotherapy
• Time between diagnosis and surgery or chemotherapy or radiotherapy or combined therapy,
Clinical test data
• full blood count results, blood biochemistry results, tumour marker results, tumour detection results (X-ray, CT scan, colonoscopy)

Lifestyle data
• smoking status, alcohol use, illicit drug use
• diet (Myfood 24 summary data)
• physical activity (7 item questionnaire, actimetry)
• number of prescribed and complementary medicines,
Health-related quality of life (HRQoL) data
• EOTRC C30 score, EORTC C29 score, HADS score,
Biological sample data
• Tumour and blood genetic signatures/profile
• Tumour and blood proteomic signatures/profile
• Tumour , blood and faecal metabolomic signatures/profile
• Tumour and circulating immune cell and inflammatory mediators profile
• Gastrointestinal microbiome genetic diversity profile

PRIMARY OUTCOME ANALYSIS
The primary endpoint is the establishment of the clinical and patient-reported database and biobank. Thus, no statistical analysis will be conducted for this endpoint.

SECONDARY OUTCOME ANALYSIS
The secondary endpoints are exploratory in nature and aimed to
2a) to define the optimal, individualized, evidence-based treatment recommendations and support pathways for treating CRC in the community.
2b) to better understand the biological processes of colorectal cancer and identify novel predictors of outcomes or new drug targets.

To be able to address aim 2a and 2b, we will need to conduct 4 major exploratory statistical analyses;
a) Clinical patterns of care
b) Longitudinal changes in lifestyle, biological sample and HRQoL data
c) Correlations between covariates
d) Correlations with covariates and clinical outcomes or HRQoL

ANALYSIS PRINCIPLES
1. All analyses will be conducted on an intention-to-treat basis.
2. All tests are two-sided and the nominal level of a will be 5%.
3. All statistical analyses will be unadjusted except where indicated.
4. Subgroup analyses will be carried out irrespective of whether there is a significant
effect of treatment on the primary outcome.
5. We will not impute missing values unless specified otherwise. Where the number of
missing observations is substantial, we will report the number of observations used in the analysis. Last observations will not be carried forward for continuous outcomes.
6. Missing data on questionnaires will be handled as per individual PRO guidelines. Mixed models are valid for data that are missing completely at random and missing at random; patterns of missing data will be assessed to consider potential missing data mechanisms. Sensitivity analysis using multiple imputation will be carried out. Baseline characteristics of participants lost to follow-up will be compared to those who completed follow-up to assess patterns of loss to follow-up, detect any difference in baseline characteristics and thus to provide insights into generalizability of the results.
7. P-values will not be adjusted for multiplicity.

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
Actual
11/10/2017
Date of last participant enrolment
Anticipated
31/12/2019
Actual
Date of last data collection
Anticipated
30/06/2029
Actual
Sample size
Target
1000
Accrual to date
8
Final
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 8918 0
Royal North Shore Hospital - St Leonards
Recruitment hospital [2] 8919 0
North Shore Private Hospital - St Leonards
Recruitment hospital [3] 8920 0
Northern Cancer Institute - St Leonards
Recruitment postcode(s) [1] 17291 0
2065 - St Leonards

Funding & Sponsors
Funding source category [1] 297379 0
University
Name [1] 297379 0
The University of Sydney
Country [1] 297379 0
Australia
Primary sponsor type
University
Name
The University of Sydney
Address
The University of Sydney, NSW 2006 Australia.
Country
Australia
Secondary sponsor category [1] 296404 0
Other Collaborative groups
Name [1] 296404 0
Sydney Vital Translational Research Centre
Address [1] 296404 0
Sydney Vital, Translational Cancer Research
Level 8, Kolling Building, RNSH
St Leonards, NSW, 2065
Country [1] 296404 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 298480 0
Sydney Local Health District - Human Research Ethics Committee (Concord Repatriation General Hospital)
Ethics committee address [1] 298480 0
Ethics committee country [1] 298480 0
Australia
Date submitted for ethics approval [1] 298480 0
23/02/2016
Approval date [1] 298480 0
09/06/2016
Ethics approval number [1] 298480 0
HREC/16/CRGH/33
Ethics committee name [2] 298517 0
North Shore Private Ethics Committee
Ethics committee address [2] 298517 0
Ethics committee country [2] 298517 0
Australia
Date submitted for ethics approval [2] 298517 0
18/05/2016
Approval date [2] 298517 0
30/08/2016
Ethics approval number [2] 298517 0
2016-004

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 77218 0
A/Prof Kellie Charles
Address 77218 0
Room 773a, Level 7
Molecular Biosciences Building (G08), University of Sydney, NSW, 2006
Country 77218 0
Australia
Phone 77218 0
+61 2 9036 5239
Fax 77218 0
Email 77218 0
[email protected]
Contact person for public queries
Name 77219 0
Hannah Powell
Address 77219 0
Rm 751, Molecular Biosciences Building GO8 | The University of Sydney | NSW | 2006
Country 77219 0
Australia
Phone 77219 0
+61293517634
Fax 77219 0
Email 77219 0
[email protected]
Contact person for scientific queries
Name 77220 0
Kellie Charles
Address 77220 0
Room 773a, Level 7
Molecular Biosciences Building (G08), University of Sydney, NSW, 2006
Country 77220 0
Australia
Phone 77220 0
+61290365239
Fax 77220 0
Email 77220 0
[email protected]

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No Supporting Document Provided



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