Clinical trial NCT00565708: Aspirin for Dukes C and High Risk Dukes B Colorectal Cancers
Official title: Aspirin for Dukes C and High Risk Dukes B Colorectal Cancers - An International, Multi-Center, Double Blind, Randomized Placebo Controlled Phase III Trial
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Colorectal Cancer
Keywords: stage II colon cancer
stage III colon cancer
stage II rectal cancer
stage III rectal cancer
Lead sponsor: National Cancer Centre, Singapore
Sponsor class: OTHER
Collaborators: name: Australasian Gastro-Intestinal Trials Group
name: INDOX Cancer Research Network
name: University of Sydney
First posted: 2007-11-30
Enrollment: 1587
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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

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)

Primary outcomes:
measure: Disease-free survival
timeFrame: 5 years
Secondary outcomes:
measure: Overall survival
timeFrame: 5 years
Other outcomes:
Locations:
city: Bankstown
country: Australia
facility: Bankstown-Lidcombe Hospital Bankstown Cancer Centre
state: New South Wales
city: Campbelltown
country: Australia
facility: Macarthur Cancer Therapy Centre
state: New South Wales
city: Camperdown
country: Australia
facility: Chris O'Brien Lifehouse, Clinical Research Centre
state: New South Wales
city: Coffs Harbour
country: Australia
facility: Coffs Harbour Health Campus North Coast Cancer Institute
state: New South Wales
city: Gosford
country: Australia
facility: Central Coast Cancer Centre Gosford Hospital
state: New South Wales
city: New Lambton Heights
country: Australia
facility: Newcastle private Hospital
state: New South Wales
city: Orange
country: Australia
facility: Orange Health Service
state: New South Wales
city: Port Macquarie
country: Australia
facility: Port Macquarie Base Hospital North Coast Cancer Institute
state: New South Wales
city: St Leonards
country: Australia
facility: Northern Cancer Institute, St Leonards
state: New South Wales
city: Sydney
country: Australia
facility: St Vincent's Hospital
state: New South Wales
city: Tamworth
country: Australia
facility: Northwest Cancer Centre Tamworth Hospital
state: New South Wales
city: Tweed Heads
country: Australia
facility: The Tweed Hospital
state: New South Wales
city: Waratah
country: Australia
facility: Calvary Mater Newcastle Hospital
state: New South Wales
city: Tiwi
country: Australia
facility: Royal Darwin Hospital
state: Northern Territory
city: Douglas
country: Australia
facility: Townsville Hospital
state: Queensland
city: Herston
country: Australia
facility: Royal Brisbane and Women's Hospital
state: Queensland
city: Toowoomba
country: Australia
facility: Toowoomba Hospital
state: Queensland
city: Elizabeth Vale
country: Australia
facility: Lyell McEwin Hospital
state: South Australia
city: Hobart
country: Australia
facility: Royal Hobart Hospital
state: Tasmania
city: Albury
country: Australia
facility: Border Medical Oncology Research Unit
state: Victoria
city: Ballarat
country: Australia
facility: Ballarat Regional Integrated Cancer Centre
state: Victoria
city: Geelong
country: Australia
facility: Barwon Health Andrew Love Cancer Centre
state: Victoria
city: Heidelberg
country: Australia
facility: Austin Health Cancer Clinical Trials
state: Victoria
city: Launceston
country: Australia
facility: Launceston General Hospital
state: Victoria
city: Melbourne
country: Australia
facility: Monash Health Medical Oncology
state: Victoria
city: Shepparton
country: Australia
facility: Goulburn Valley Health
state: Victoria
city: Warrnambool
country: Australia
facility: St John of God Healthcare Southwest Oncology
state: Victoria
city: Nedlands
country: Australia
facility: Sir Charles Gairdner Hospital
state: Western Australia
city: Subiaco
country: Australia
facility: St John of God Hospital Subiaco
state: Western Australia
city: Beijing
country: China
facility: Beijing University Cancer Hospital
state: Beijing
city: Foshan
country: China
facility: The First People's Hospital of Foshan City
state: Guangdong
city: Guangzhou
country: China
facility: Guangdong General Hospital
state: Guangdong
city: Guangzhou
country: China
facility: Sixth Affiliated Hospital
state: Guangdong
city: Guangzhou
country: China
facility: Sun Yat Sen University Cancer Center
state: Guangdong
city: Zhongshan
country: China
facility: Zhongshan City People's Hospital
state: Guangdong
city: Nantong
country: China
facility: Affiliated Hospital of Nantong University
state: Jiangsu
city: Jinan
country: China
facility: Jinan Central Hospital
state: Shandong
city: Yantai
country: China
facility: Yantai Yuhuangding Hospital
state: Shandong
city: Taibei
country: China
facility: Shuang Ho Hospital
state: Taiwan
city: Taibei
country: China
facility: Koo Foundation Sun Yat Sen Cancer Centre
state: Taiwan
city: Taibei
country: China
facility: Taipei Medical University Hospital
state: Taiwan
city: Taibei
country: China
facility: Wan Fang Hospital
state: Taiwan
city: Hangzhou
country: China
facility: The Second Affiliated Hospital of Zhejiang University
state: Zhejiang
city: Hong Kong
country: China
facility: Queen Mary Hospital - Hong Kong
city: Bangalore
country: India
facility: Kidwai Memorial Institute of Oncology
city: Coimbatore
country: India
facility: G. Kuppuswamy Naidu Memorial Hospital
city: Hyderabad
country: India
facility: Nizam's Institute of Medical Sciences
city: Mumbai
country: India
facility: Tata Memorial Hospital
city: New Delhi
country: India
facility: All India Institute of Medical Sciences
city: Trivandrum
country: India
facility: Regional Cancer Center
city: Vellore
country: India
facility: Christian Medical College and Hospital
city: Jakarta
country: Indonesia
facility: Dharmais Cancer Hospital
city: Jakarta
country: Indonesia
facility: Cipto Mangunkusumo General Hospital
city: Yogyakarta
country: Indonesia
facility: Rumah Sakit RSUP Dr. Sardjito
city: Anyang-si
country: Korea, Republic of
facility: Hallym University Sacred Heart Hospital
state: Gyeonggi-do
city: Seoul
country: Korea, Republic of
facility: Severance Hospital
city: Kuching
country: Malaysia
facility: Sarawak General Hospital
state: Sarawak
city: Kuala Lumpur
country: Malaysia
facility: Hospital Kuala Lumpur
city: Kuala Lumpur
country: Malaysia
facility: University of Malaysia Medical Center
city: Kuala Lumpur
country: Malaysia
facility: University Kebangsaan Malaysia Medical Center
city: Christchurch
country: New Zealand
facility: Christchurch Public Hospital
city: Dunedin
country: New Zealand
facility: Dunedin Hospital
city: Riyadh
country: Saudi Arabia
facility: King Fahad Medical City
city: Singapore
country: Singapore
facility: National Cancer Centre - Singapore
city: Singapore
country: Singapore
facility: Johns Hopkins Singapore International Medical Center
city: Singapore
country: Singapore
facility: Tan Tock Seng Hospital
city: Maharagama
country: Sri Lanka
facility: National Cancer Institute
Study officials:
affiliation: National Cancer Centre, Singapore
name: John Chia, MBBS, MRCP
role: STUDY_CHAIR
affiliation: NYU
name: Raghib Ali, MBBS,MRCP
role: STUDY_CHAIR
affiliation: National Cancer Centre, Singapore
name: Han Chong Toh, MD,MBBS,MRCP
role: STUDY_CHAIR
affiliation: Monash University, University of Bern
name: Eva Segelov, MBBS,PhD
role: STUDY_CHAIR
References:
citation: 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.
citation: 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.
citation: 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.