Aspirin for Dukes C and High Risk Dukes B Colorectal Cancers

NCT ID: NCT00565708

Last Updated: 2024-02-02

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE3
• Total Enrollment: 1587 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2008-12-31
• Study Completion Date: 2024-06-30

Brief Summary

We hypothesize through this randomized, placebo-controlled adjuvant study, that Aspirin in patients with dukes C or high risk dukes B colorectal cancer (ASCOLT) can improve survival in this patient population over placebo control. If indeed found to be beneficial, because aspirin is cheap and easy to administer, it will positively impact the lives of many individuals in Asia and globally.

STUDY OBJECTIVE

To assess the effectiveness of Aspirin against placebo control in patients with dukes C or high risk dukes B colorectal cancer in terms of Disease Free Survival (DFS) and Overall Survival (OS)

Primary endpoints

• DFS among all eligible subjects (high risk Dukes B colon cancer, Dukes C colon cancer and rectal cancer patient sub-groups);
• DFS among patients with colon cancer (high-risk Dukes B and Dukes C colon cancer).

Secondary endpoints

• Overall survival (OS) over 5 years
• DFS and OS in

• Chinese, Malay, Indian and other ethnic groups
• Resected high risk Dukes B colon cancer, Dukes C colon cancer and rectal cancer sub-groups, individually
• Compliant versus non-compliant subjects
• PIK3CA mutated tumors (where samples are available)

Detailed Description

Aspirin in patients with dukes C or high risk dukes B colorectal cancer can improve survival in this patient population over placebo control.

Eligible patients will be randomized to treatment arms, using the following stratification factors:

• Study Centre
• Tumour Type
• Type of adjuvant chemotherapy received(exposed/not exposed to oxaliplatin

Patients will be randomized over a 5 years' time period. After randomization, patient will have 3 monthly assessments with treatment for 3 years followed by 6 monthly assessments for additional 2 years follow-up

Conditions

Colorectal Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

acetylsalicylic acid

200mg OD for 3 years

Group Type: EXPERIMENTAL

Acetylsalicylic acid

Intervention Type: DRUG

Adjuvant Therapy

Placebo

200mg OD for 3 years

Group Type: PLACEBO_COMPARATOR

placebo

Intervention Type: OTHER

Placebo Comparator

Interventions

placebo

Placebo Comparator

Intervention Type: OTHER

Acetylsalicylic acid

Adjuvant Therapy

Intervention Type: DRUG

Other Intervention Names

Aspirin

Eligibility Criteria

Inclusion Criteria

• Male or female outpatient of ≥ 18 years of age or ≥ 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 (see Appendix 1 for definition of High Risk Dukes B)
• Undergone complete resection of primary tumour
• Completed standard therapy ( at least 3 months of chemotherapy ± radiotherapy )
• Within 120 days of completion of standard therapy (surgery, chemotherapy ± 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 Group
• ANC ≥ 1.0 x 109/L
• Platelets ≥ 100 x 109/L
• Creatinine clearance ≥ 30 mL/min
• Total bilirubin ≤ 2.0 x the upper limit normal
• AST & ALT ≤ 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

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 (≥ 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)

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Australasian Gastro-Intestinal Trials Group

NETWORK

Sponsor Role: collaborator

INDOX Cancer Research Network

OTHER

Sponsor Role: collaborator

University of Sydney

OTHER

Sponsor Role: collaborator

National Cancer Centre, Singapore

OTHER

Sponsor Role: lead

Responsible Party

Toh Han Chong

Prof

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

John Chia, MBBS, MRCP

Role: STUDY_CHAIR

National Cancer Centre, Singapore

Raghib Ali, MBBS,MRCP

Role: STUDY_CHAIR

NYU

Han Chong Toh, MD,MBBS,MRCP

Role: STUDY_CHAIR

National Cancer Centre, Singapore

Eva Segelov, MBBS,PhD

Role: STUDY_CHAIR

Monash University, University of Bern

Locations

Bankstown-Lidcombe Hospital Bankstown Cancer Centre

Bankstown, New South Wales, Australia

Macarthur Cancer Therapy Centre

Campbelltown, New South Wales, Australia

Chris O'Brien Lifehouse, Clinical Research Centre

Camperdown, New South Wales, Australia

Coffs Harbour Health Campus North Coast Cancer Institute

Coffs Harbour, New South Wales, Australia

Central Coast Cancer Centre Gosford Hospital

Gosford, New South Wales, Australia

Newcastle private Hospital

New Lambton Heights, New South Wales, Australia

Orange Health Service

Orange, New South Wales, Australia

Port Macquarie Base Hospital North Coast Cancer Institute

Port Macquarie, New South Wales, Australia

Northern Cancer Institute, St Leonards

St Leonards, New South Wales, Australia

St Vincent's Hospital

Sydney, New South Wales, Australia

Northwest Cancer Centre Tamworth Hospital

Tamworth, New South Wales, Australia

The Tweed Hospital

Tweed Heads, New South Wales, Australia

Calvary Mater Newcastle Hospital

Waratah, New South Wales, Australia

Royal Darwin Hospital

Tiwi, Northern Territory, Australia

Townsville Hospital

Douglas, Queensland, Australia

Royal Brisbane and Women's Hospital

Herston, Queensland, Australia

Toowoomba Hospital

Toowoomba, Queensland, Australia

Lyell McEwin Hospital

Elizabeth Vale, South Australia, Australia

Royal Hobart Hospital

Hobart, Tasmania, Australia

Border Medical Oncology Research Unit

Albury, Victoria, Australia

Ballarat Regional Integrated Cancer Centre

Ballarat, Victoria, Australia

Barwon Health Andrew Love Cancer Centre

Geelong, Victoria, Australia

Austin Health Cancer Clinical Trials

Heidelberg, Victoria, Australia

Launceston General Hospital

Launceston, Victoria, Australia

Monash Health Medical Oncology

Melbourne, Victoria, Australia

Goulburn Valley Health

Shepparton, Victoria, Australia

St John of God Healthcare Southwest Oncology

Warrnambool, Victoria, Australia

Sir Charles Gairdner Hospital

Nedlands, Western Australia, Australia

St John of God Hospital Subiaco

Subiaco, Western Australia, Australia

Beijing University Cancer Hospital

Beijing, Beijing Municipality, China

The First People's Hospital of Foshan City

Foshan, Guangdong, China

Guangdong General Hospital

Guangzhou, Guangdong, China

Sixth Affiliated Hospital

Guangzhou, Guangdong, China

Sun Yat Sen University Cancer Center

Guangzhou, Guangdong, China

Zhongshan City People's Hospital

Zhongshan, Guangdong, China

Affiliated Hospital of Nantong University

Nantong, Jiangsu, China

Jinan Central Hospital

Jinan, Shandong, China

Yantai Yuhuangding Hospital

Yantai, Shandong, China

Shuang Ho Hospital

Taibei, Taiwan, China

Koo Foundation Sun Yat Sen Cancer Centre

Taibei, Taiwan, China

Taipei Medical University Hospital

Taibei, Taiwan, China

Wan Fang Hospital

Taibei, Taiwan, China

The Second Affiliated Hospital of Zhejiang University

Hangzhou, Zhejiang, China

Queen Mary Hospital - Hong Kong

Hong Kong, , China

Kidwai Memorial Institute of Oncology

Bangalore, , India

G. Kuppuswamy Naidu Memorial Hospital

Coimbatore, , India

Nizam's Institute of Medical Sciences

Hyderabad, , India

Tata Memorial Hospital

Mumbai, , India

All India Institute of Medical Sciences

New Delhi, , India

Regional Cancer Center

Trivandrum, , India

Christian Medical College and Hospital

Vellore, , India

Dharmais Cancer Hospital

Jakarta, , Indonesia

Cipto Mangunkusumo General Hospital

Jakarta, , Indonesia

Rumah Sakit RSUP Dr. Sardjito

Yogyakarta, , Indonesia

Sarawak General Hospital

Kuching, Sarawak, Malaysia

Hospital Kuala Lumpur

Kuala Lumpur, , Malaysia

University of Malaysia Medical Center

Kuala Lumpur, , Malaysia

University Kebangsaan Malaysia Medical Center

Kuala Lumpur, , Malaysia

Christchurch Public Hospital

Christchurch, , New Zealand

Dunedin Hospital

Dunedin, , New Zealand

King Fahad Medical City

Riyadh, , Saudi Arabia

National Cancer Centre - Singapore

Singapore, , Singapore

Johns Hopkins Singapore International Medical Center

Singapore, , Singapore

Tan Tock Seng Hospital

Singapore, , Singapore

Hallym University Sacred Heart Hospital

Anyang-si, Gyeonggi-do, South Korea

Severance Hospital

Seoul, , South Korea

National Cancer Institute

Maharagama, , Sri Lanka

Countries

Australia; China; India; Indonesia; Malaysia; New Zealand; Saudi Arabia; Singapore; South Korea; Sri Lanka

References

Segelov E, Prenen H, Day D, Macintyre CR, Foo EMJ, Ali R, Wang Q, Wei X, Lopes GL Jr, Ding K, Chen G, Chia JWK, Toh HC; ASCOLT Investigators. Impact of the COVID-19 Epidemic on a Pan-Asian Academic Oncology Clinical Trial. JCO Glob Oncol. 2020 Apr;6:585-588. doi: 10.1200/GO.20.00072. No abstract available.

Reference Type: BACKGROUND

PMID: 32293940 (View on PubMed)

Day D, Toh HC, Ali R, Foo EMJ, Simes J, Chia JWK, Segelov E; ASCOLT Investigators. Operational Challenges of an Asia-Pacific Academic Oncology Clinical Trial. JCO Glob Oncol. 2023 Jun;9:e2300040. doi: 10.1200/GO.23.00040.

Reference Type: BACKGROUND

PMID: 37364220 (View on PubMed)

Chia JWK, Segelov E, Deng Y, Ho GF, Wang W, Han S, Sharma A, Ding K, Chen G, Jeffery MG, Tham CK, Ahn JB, Nott L, Zielinski R, Chao TY, van Hagen T, Wei PL, Day F, Mehta S, Yau T, Peng J, Hayes TM, Li Y, Gandhi M, Foo EMJ, Rahman N, Rothwell P, Ali R, Simes J, Toh HC. Aspirin after completion of standard adjuvant therapy for colorectal cancer (ASCOLT): an international, multicentre, phase 3, randomised, double-blind, placebo-controlled trial. Lancet Gastroenterol Hepatol. 2025 Mar;10(3):198-209. doi: 10.1016/S2468-1253(24)00387-X. Epub 2025 Jan 14.

Reference Type: DERIVED

PMID: 39824200 (View on PubMed)

Ali R, Toh HC, Chia WK; ASCOLT Trial Investigators. The utility of Aspirin in Dukes C and High Risk Dukes B Colorectal cancer--the ASCOLT study: study protocol for a randomized controlled trial. Trials. 2011 Dec 14;12:261. doi: 10.1186/1745-6215-12-261.

Reference Type: DERIVED

PMID: 22168568 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

SINGAPORE-ICR-02

Identifier Type: OTHER

Identifier Source: secondary_id

SINGAPORE-ASCOLT

Identifier Type: OTHER

Identifier Source: secondary_id

CDR0000577892

Identifier Type: -

Identifier Source: org_study_id