Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12614000513617
Ethics application status
Approved
Date submitted
29/04/2014
Date registered
15/05/2014
Date last updated
21/02/2023
Date data sharing statement initially provided
7/08/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
ASCOLT
Aspirin for Dukes C and High Risk Dukes B Colorectal Cancers.
Scientific title
ASCOLT
Aspirin for Dukes C and High Risk Dukes B Colorectal Cancers.
An International, Multi-centre, Double Blind, Randomised Placebo Controlled Phase III Trial
Secondary ID [1] 284287 0
Nil
Universal Trial Number (UTN)
Trial acronym
ASCOLT
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Colorectal Cancer 291431 0
Condition category
Condition code
Cancer 291798 291798 0 0
Bowel - Back passage (rectum) or large bowel (colon)

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Eligible participants will be randomised to the study in 1:1 ration to either Aspirin arm: 200 mg Aspirin (oral tablet) once a day for 3 years or Placebo equivalent.

The study treatment is given as adjuvant therapy

Drug compliance will be monitored via drug dispensations and drug returns, recorded on drug accountability logs at each study visit.

Noncompliance is defined as omission of more than 30% of the study period that the patient is on the study.
Intervention code [1] 289006 0
Treatment: Drugs
Comparator / control treatment
Placebo arm: 200 mg matching placebo once a day for 3 years.

The study treatment is given as adjuvant therapy
Control group
Placebo

Outcomes
Primary outcome [1] 291721 0
Disease Free Survival (DFS) among all eligible subjects (high risk Dukes B colon cancer, Dukes C colon cancer and rectal cancer patient sub-groups)
Timepoint [1] 291721 0
During treatment: prior to each treatment cycle. Patient will have 3 monthly assessments for 3 years (month 3 to month 36) followed by 6 monthly assessments for additional 2 years (month 42 to month 60).
Secondary outcome [1] 307352 0
- Overall survival (OS) over 5 years
Timepoint [1] 307352 0
Patient will have 3 monthly assessments for 3 years (month 3 to month 36) followed by 6 monthly assessments for additional 2 years (month 42 to month 60).
Secondary outcome [2] 307353 0
Quality of Life assessed in ANZ region by completion of Quality of Life Questionnaires EQ-5D-5L, EORTC QLQ-C30 and CR29 (colorectal module)
Timepoint [2] 307353 0
These will be completed prior to study treatment (baseline), again after 12 months of treatment and at the end of study after 36 months of treatment.
Secondary outcome [3] 308029 0
Disease Free Survival and OS in
> Chinese, Malay, Indian and other ethnic groups
Timepoint [3] 308029 0
Patient will have 3 monthly assessments for 3 years (month 3 to month 36) followed by 6 monthly assessments for additional 2 years (month 42 to month 60).
Secondary outcome [4] 308030 0
Disease Free Survival and OS in
> Resected high risk Dukes B colon cancer, Dukes C colon
cancer and rectal cancer sub-groups, individually
Timepoint [4] 308030 0
Patient will have 3 monthly assessments for 3 years (month 3 to month 36) followed by 6 monthly assessments for additional 2 years (month 42 to month 60).
Secondary outcome [5] 308031 0
Disease Free Survival and OS in
> Compliant versus non-compliant subjects
Timepoint [5] 308031 0
Patient will have 3 monthly assessments for 3 years (month 3 to month 36) followed by 6 monthly assessments for additional 2 years (month 42 to month 60).
Secondary outcome [6] 308032 0
Disease Free Survival and OS in
> PIK3CA mutated tumors (where samples are available)
Timepoint [6] 308032 0
Patient will have 3 monthly assessments for 3 years (month 3 to month 36) followed by 6 monthly assessments for additional 2 years (month 42 to month 60).

Eligibility
Key inclusion criteria
- Male or female outpatient of at least 18 years of age or at least the country's legal age for adult consent
- Dukes C colon cancer, high risk Dukes B colon cancer, Dukes B rectal cancer or Dukes C rectal cancer
- Undergone complete resection of primary tumour
- Completed standard therapy (at least 3 months of chemotherapy with or without radiotherapy)
- Within 120 days of completion of standard therapy (surgery, chemotherapy with or without radiotherapy)
- ECOG performance status 0 to 2

- Satisfactory haematological or biochemical functions (tests should be carried out within 8 weeks prior to randomisation): Results of clinical investigations carried out within 8 weeks prior to randomisation can be used in place of the required screening investigations. Patients with mild laboratory abnormalities can be included at the discretion by the site principal investigator, and after approval by ASCOLT Trial Management GroupB-F57
- ANC greater than or equal to 1.0 x 109/L
- Platelets greater than or equal to 100 x 109/L
- Creatinine clearance greater than or equal to 30 mL/min
- Total bilirubin less than or equal to 2.0 x the upper limit
normal
- AST & ALT less than or equal to 5 x the upper limit
normal

- Completed the following investigations
- Colonoscopy (or CT colonogram) within 16 months prior
to randomization
- Imaging of abdomen (CT or CT colonogram or MRI or
PET or Ultrasound) within 16 months prior to
randomization

- Written informed consent
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- Pre-existing Familial adenomatous polyposis, inflammatory
bowel disease or ulcerative colitis
- Active gastritis or active peptic ulcer
- History of continuous daily use of PPI more than 1 year
prior to consent
- Gastrointestinal bleeding within the past one year
- Haemorrhagic diathesis (i.e. haemophilia)
- Uncontrolled hypertension (untreated systolic blood
pressure > 160 mmHg, or diastolic blood pressure > 95
mmHg)
- History of recent cancers (except for colorectal cancers,
non-melanoma skin cancers, basal cell carcinomas,
squamous cell carcinomas) in the past 5 years
- History of stroke, coronary arterial disease, angina, or
vascular disease
- Patients who are on current long term treatment (greater
than or equal to 4 consecutive weeks) with Aspirin, NSAID
or Cox-2 inhibitors
- History of erosive GERD or active erosive GERD on
gastroscopy.
- Patient on active current treatment of antiplatelet agents
(i.e. off-study Aspirin, clopidogrel, ticlopidine)
- Patient receiving active treatment of anticoagulants
(i.e. warfarin, low molecular weight heparins)
- Pregnant, lactating, or not using adequate contraception
- Patient having known allergy to NSAID or Aspirin
- Unexplained rise of CEA (i.e. smoker with elevated CEA will
not be excluded)
- Patient on other investigational drug
- Patients with HNPCC (Lynch Syndrome)

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Randomisation will occur within 120 days of completion of standard therapy. After informed consent is signed and participant eligibility is confirmed, the participant can be randomised in a 1:1 allocation ratio, to receive either Aspirin (oral tablet) or a matched placebo for 3 years.

Randomisation will be done via central randomisation website: Authorized study centre personnel will randomise the patient via a password-protected internet web site. The randomisation system will then allocate the treatment arm and provide the subject number to be used for the patient. The treatment arm will not be disclosed. The Clinical Trial Centre will be informed immediately in the event that the web randomisation is not successful.

The patient, the study team including the investigator(s) and the sponsor will be blinded. Sealed Code break envelopes will be provided for emergency unblinding.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Stratification factors include,
- Study centre
- Tumour type (Dukes C colon, high risk Dukes B colon
cancer, and rectal cancer sub-groups) and
- Type of adjuvant chemotherapy received (exposed/ not
exposed to oxaliplatin)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis
All statistical analyses will be carried out on an intention to treat basis.
In the analysis of disease free survival, an event of interest is a patient relapses or dies during the study period. The starting point is the date of randomisation and the end point is the date of first disease recurrence or date of death, whichever occurs first. Patients with no evidence of disease after treatment are censored at the date of last follow-up. Similarly, the overall survival time is censored at the date when the patient is last known to be alive.
Each primary endpoint will be analysed as follows. Survival curves will be constructed using the Kaplan-Meier method. Life table estimates of 3 and 5 year survival rates will be calculated. The efficacy of Aspirin will be evaluated by the Hazard Ratio (HR) and its corresponding 95% CI. A Cox proportional hazard model will be used to estimate HRs adjusting for the trial stratification factors (site, type of tumour and type of adjuvant chemotherapy). Stratified analysis and other non-proportional hazard models (which allow for the effects of covariates to vary over time) would be considered when proportional hazards assumption is not valid.
The secondary endpoint of overall survival will be analysed in a similar manner to the primary endpoints. For the subgroup analyses, tests for interaction for the colon cancer subgroups and other subgroups will be conducted first. Similar analyses of DFS and OS as presented above will be repeated within the subgroups respectively defined by ethnicity, tumour type, and patients’ compliance and according to patient’s PIK3CA mutational status. The percentage of patients with different PIK3CA mutational status will be compared by Chi-square test in the Aspirin and Placebo groups.
Total international trial size will be 1200 patients. Assuming an odds ratio of 0.72, such that an absolute difference of disease free survival rate between the two treatment groups is about 8.5%, in this case a samples size of 1200 is required for a two sided logrank test of 5% type 1 error, 80% power and 15% attrition rate.

Recruitment
Recruitment status
Active, not recruiting
Date of first participant enrolment
Anticipated
9/06/2014
Actual
28/08/2014
Date of last participant enrolment
Anticipated
31/12/2020
Actual
30/06/2021
Date of last data collection
Anticipated
31/07/2026
Actual
Sample size
Target
460
Accrual to date
Final
476
Recruitment in Australia
Recruitment state(s)
NSW,QLD,SA,TAS,WA,VIC
Recruitment hospital [1] 6276 0
Newcastle Private Hospital - New Lambton Heights
Recruitment hospital [2] 6277 0
Orange Health Service - Orange
Recruitment hospital [3] 6278 0
Tamworth Rural Referral Hospital - Tamworth
Recruitment hospital [4] 6279 0
The Townsville Hospital - Douglas
Recruitment hospital [5] 6280 0
Port Macquarie Base Hospital - Port Macquarie
Recruitment hospital [6] 6281 0
Calvary Mater Newcastle - Waratah
Recruitment hospital [7] 6282 0
Royal Brisbane & Womens Hospital - Herston
Recruitment hospital [8] 6283 0
The Tweed Hospital - Tweed Heads
Recruitment hospital [9] 6284 0
Royal Hobart Hospital - Hobart
Recruitment hospital [10] 6285 0
Bankstown-Lidcombe Hospital - Bankstown
Recruitment hospital [11] 6286 0
Monash Medical Centre - Clayton campus - Clayton
Recruitment hospital [12] 6287 0
Barwon Health - Geelong Hospital campus - Geelong
Recruitment hospital [13] 6288 0
Lyell McEwin Hospital - Elizabeth Vale
Recruitment hospital [14] 6289 0
Campbelltown Hospital - Campbelltown
Recruitment hospital [15] 6290 0
Austin Health - Austin Hospital - Heidelberg
Recruitment hospital [16] 6291 0
Sir Charles Gairdner Hospital - Nedlands
Recruitment hospital [17] 6292 0
St John of God Hospital, Subiaco - Subiaco
Recruitment hospital [18] 6293 0
Northern Cancer Institute - St Leonards
Recruitment hospital [19] 6294 0
Coffs Harbour Base Hospital - Coffs Harbour
Recruitment hospital [20] 6295 0
Gosford Hospital - Gosford
Recruitment hospital [21] 6296 0
Goulburn Valley Health - Shepparton campus - Shepparton
Recruitment hospital [22] 6297 0
Royal Darwin Hospital - Tiwi
Recruitment hospital [23] 6298 0
Border Medical Oncology - Albury
Recruitment hospital [24] 6299 0
Ballarat Health Services (Base Hospital) - Ballarat Central
Recruitment hospital [25] 6300 0
The Chris O’Brien Lifehouse - Camperdown
Recruitment hospital [26] 7463 0
Southwest Health Care - Warrnambool - Warrnambool
Recruitment hospital [27] 10073 0
Launceston General Hospital - Launceston
Recruitment hospital [28] 10074 0
St Vincent's Hospital (Darlinghurst) - Darlinghurst
Recruitment hospital [29] 10075 0
Mildura Base Hospital - Mildura
Recruitment hospital [30] 10076 0
Toowoomba Hospital - Toowoomba
Recruitment postcode(s) [1] 13811 0
3690 - Wodonga
Recruitment postcode(s) [2] 13812 0
2065 - St Leonards
Recruitment postcode(s) [3] 13813 0
0800 - Darwin
Recruitment postcode(s) [4] 13814 0
2250 - Gosford
Recruitment postcode(s) [5] 13815 0
2050 - Camperdown
Recruitment postcode(s) [6] 13816 0
3350 - Ballarat
Recruitment postcode(s) [7] 13817 0
3630 - Shepparton
Recruitment postcode(s) [8] 13818 0
2340 - Tamworth
Recruitment postcode(s) [9] 13819 0
4810 - Townsville
Recruitment postcode(s) [10] 13820 0
2450 - Coffs Harbour
Recruitment postcode(s) [11] 13821 0
2298 - Waratah
Recruitment postcode(s) [12] 13822 0
2444 - Port Macquarie
Recruitment postcode(s) [13] 13823 0
3220 - Geelong
Recruitment postcode(s) [14] 13824 0
3084 - Heidelberg
Recruitment postcode(s) [15] 13825 0
2485 - Tweed Heads
Recruitment postcode(s) [16] 13826 0
6008 - Subiaco
Recruitment postcode(s) [17] 13827 0
6009 - Nedlands
Recruitment postcode(s) [18] 13828 0
7000 - Hobart
Recruitment postcode(s) [19] 13829 0
2305 - New Lambton Heights
Recruitment postcode(s) [20] 13830 0
4006 - Herston
Recruitment postcode(s) [21] 13831 0
2200 - Bankstown
Recruitment postcode(s) [22] 13832 0
3168 - Clayton
Recruitment postcode(s) [23] 13833 0
5112 - Elizabeth Vale
Recruitment postcode(s) [24] 13834 0
2560 - Campbelltown
Recruitment postcode(s) [25] 15289 0
3280 - Warrnambool
Recruitment postcode(s) [26] 15290 0
3280 - Warrnambool
Recruitment postcode(s) [27] 21599 0
7250 - Launceston
Recruitment postcode(s) [28] 21600 0
2010 - Darlinghurst
Recruitment postcode(s) [29] 21601 0
3500 - Mildura
Recruitment postcode(s) [30] 21602 0
4350 - Toowoomba
Recruitment outside Australia
Country [1] 5902 0
New Zealand
State/province [1] 5902 0
Canterbury and Otago
Country [2] 5903 0
Singapore
State/province [2] 5903 0
Country [3] 8054 0
Singapore
State/province [3] 8054 0
Country [4] 8055 0
Singapore
State/province [4] 8055 0

Funding & Sponsors
Funding source category [1] 288914 0
Government body
Name [1] 288914 0
Cancer Australia
Country [1] 288914 0
Australia
Funding source category [2] 288915 0
Government body
Name [2] 288915 0
Bowel Cancer Australia
Country [2] 288915 0
Australia
Primary sponsor type
Other Collaborative groups
Name
Australasian Gastro-Intestinal Trial Group (AGITG)
Address
NHMRC Clinical Trials Centre
Locked Bag 77
Camperdown NSW 1450
Country
Australia
Secondary sponsor category [1] 287610 0
None
Name [1] 287610 0
Address [1] 287610 0
Country [1] 287610 0
Other collaborator category [1] 277883 0
Other Collaborative groups
Name [1] 277883 0
National Cancer Centre
Department of Medical Oncology
Address [1] 277883 0
11 Hospital Drive
Singapore 169610
Country [1] 277883 0
Singapore

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 290745 0
SLHD Ethics Review Committee (RPAH Zone) (EC00113)
Ethics committee address [1] 290745 0
Ethics committee country [1] 290745 0
Australia
Date submitted for ethics approval [1] 290745 0
03/10/2013
Approval date [1] 290745 0
12/03/2014
Ethics approval number [1] 290745 0
HREC/13/RPAH/507

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

Contacts
Principal investigator
Name 47042 0
A/Prof Eva Segelov
Address 47042 0
NHMCR CTC
Locked Bag 77
Camperdown, NSW, 1450
Country 47042 0
Australia
Phone 47042 0
61 2 9562 5000
Fax 47042 0
61 2 9562 5094
Email 47042 0
[email protected]
Contact person for public queries
Name 47043 0
ASCOLT Trial Coordinator
Address 47043 0
NHMCR CTC
Locked Bag 77
Camperdown, NSW, 1450
Country 47043 0
Australia
Phone 47043 0
61 2 9562 5000
Fax 47043 0
61 2 9562 5094
Email 47043 0
[email protected]
Contact person for scientific queries
Name 47044 0
ASCOLT Trial Coordinator
Address 47044 0
NHMCR CTC
Locked Bag 77
Camperdown, NSW, 1450
Country 47044 0
Australia
Phone 47044 0
61 2 9562 5000
Fax 47044 0
61 2 9562 5094
Email 47044 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
Contact CTC for data sharing policy.


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
SourceTitleYear of PublicationDOI
Dimensions AIImplementation of the Australasian Teletrial Model: Lessons from practice2019https://doi.org/10.1111/ajco.13249
N.B. These documents automatically identified may not have been verified by the study sponsor.