Condition category
Cancer
Date applied
21/01/2015
Date assigned
21/01/2015
Last edited
03/11/2015
Prospective/Retrospective
Prospectively registered
Overall trial status
Ongoing
Recruitment status
Recruiting

Contact information

Type

Scientific

Primary contact

Dr Marta Campos

ORCID ID

Contact details

Medical Research Council Clinical Trials Unit (MRC CTU)
Aviation House
125 Kingsway
London
WC2B 6NH
United Kingdom

Additional identifiers

EudraCT number

2013-004398-28

ClinicalTrials.gov number

Protocol/serial number

18067

Study information

Scientific title

A phase III double-blind placebo-controlled randomised trial assessing the effects of aspirin on disease recurrence and survival after primary therapy in common non-metastatic solid tumours.

Acronym

Study hypothesis

Aim: To assess whether regular aspirin use after standard cancer therapy prevents recurrence and prolongs survival in patients with early stage common solid tumours. International recruitment will allow assessment of the intervention in different communities.

Ethics approval

14/SC/0171; First MREC approval date 04/06/2014

Study design

Randomised; Interventional

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Hospitals

Trial type

Treatment

Patient information sheet

Not available in web format, please use contact details to request a patient information sheet

Condition

Cancer

Intervention

1. Randomised blinded phase: Participants will be randomly assigned to 100mg aspirin, 300mg aspirin or matched placebo. All tablets will be enteric-coated to be taken daily for at least five years
2. Run-in feasibility phase: During the feasibility phase of the study, all participants will take open label 100mg aspirin daily for a run-in period of approximately 8 weeks prior to randomisation

Intervention type

Other

Phase

Phase III

Drug names

Primary outcome measures

Overall survival

Secondary outcome measures

N/A

Overall trial start date

01/03/2015

Overall trial end date

28/02/2021

Reason abandoned

Eligibility

Participant inclusion criteria

Common inclusion criteria:
1. Written informed consent
2. WHO performance status 0, 1 or 2
3. Previous or current participants of other primary treatment trials if agreed in advance between trials
4. No clinical or radiological evidence of residual or distant disease

Breast cohort inclusion criteria:
1. Men or women with histologically confirmed invasive breast cancer
2. Undergone complete primary invasive tumour excision with clear margins
3. Surgical staging of the axilla must have been undertaken by sentinel node biopsy, axillary sampling or dissection
4. In those patients with a positive sentinel node biopsy:
4.1. If 1, 2 or 3 nodes are positive, subsequent management of the axilla (with surgery, radiotherapy or no further intervention) should be completed prior to registration
4.2. If 4 or more nodes are involved, patients must have undergone completion axillary node dissection
5. Radiotherapy (RT):
5.1. Patients who have undergone breast conserving surgery should receive adjuvant RT
5.2. Patients who have undergone mastectomy should receive RT if they have more than 3 axillary lymph nodes involved
5.3. Patients who have undergone mastectomy and have T3 tumours and/or 1, 2 or 3 involved lymph nodes may (or not) receive radiation per institutional practice
6. Final histology must fall within at least one of these 3 groups:
6.1. Node positive
6.2. Node negative with high risk features 2 or more of:
6.2.1. ER negative
6.2.2. HER2 positive
6.2.3. Grade 3
6.2.4. Lymphovascular invasion present
6.2.5. Age <35
6.2.6. Oncotype Dx score of >25
6.3. In patients who have received neoadjuvant chemotherapy, patients are eligible if they have both a hormone receptor negative/HER2 negative tumour, a HER2 positive tumour or a hormone receptor positive grade 3 tumour and did not achieve a pathological complete response with neoadjuvant systemic therapy
7. Patients who received standard neoadjuvant and/or adjuvant chemotherapy or RT are eligible
8. Known HER2 and ER status
9. Participants may receive endocrine therapy and trastuzumab. All ER positive patients should be planned to undergo at least 5 yrs of adjuvant endocrine therapy

Colorectal cohort inclusion criteria:
1. Histologically confirmed stage II or III adenocarcinoma of the colon or rectum and patients who have undergone resection of liver metastases with clear margins and no residual metastatic disease
2. Patients with synchronous tumours if one of the tumours is at least stage II or III
3. Serum CEA ideally =1.5 x upper limit of normal
4. Have undergone curative (R0) resection with clear margins

Gastroesophageal cohort inclusion criteria:
1. Patients with histologically confirmed adenocarcinoma, adenosquamous carcinoma or squamous cell cancer of the oesophagus, gastroesophageal junction or stomach
2. Have undergone curative (R0) resection with clear margins or primary chemoRT given with curative intent

Prostate cohort inclusion criteria:
1. Men with histologically confirmed node negative nonmetastatic
adenocarcinoma of the prostate
2. Have undergone curative treatment, either:
2.1. Radical prostatectomy
2.2. Radical RT
2.3. Salvage RT (following rise in PSA after prostatectomy)
3. Intermediate or high risk according to D’Amico classification

Treatment pathway specific inclusion criteria:
1. Prostatectomy patients:
1.2. Open, laparoscopic or robotic radical prostatectomy
1.3. Men treated with immediate adjuvant RT
1.4. Men receiving adjuvant hormone therapy planned for a maximum duration of 3 yrs
1.5. Men randomised to any of the 3 arms of RADICALS HD are eligible Prostatectomy patients
2. Radical RT patients:
2.1. Men receiving neoadjuvant and/or adjuvant hormone therapy planned for a
maximum duration of 3yrs
3. Salvage RT patients following PSA rise after previous radical prostatectomy:
3.1. Men treated with salvage RT following a rise in PSA are eligible
3.2. Men receiving neoand/or adjuvant hormone therapy planned for a maximum of 3yrs
3.3. Men randomised to any of the 3 arms of RADICALS HD are eligible

Participant type

Patient

Age group

Adult

Gender

Both

Target number of participants

Planned Sample Size: 11000; UK Sample Size: 9189

Participant exclusion criteria

Participants must not meet any of the common or their tumour specific exclusion criteria.

Common exclusion criteria:
1. Current or previous regular use of aspirin (at any dose) or current use of another NSAID for any indication
2. A past history of adverse reaction or hypersensitivity to NSAIDs, celecoxib, aspirin or other salicylates or sulphonamides, including asthma, that is exacerbated by use of NSAIDs
3. Current use of anticoagulants
4. Current or longterm use of oral corticosteroids. The treating physician should make the clinical decision whether a patient has been exposed to longterm therapy
5. Active or previous peptic ulceration or gastrointestinal bleeding within the last year, except where the cause of bleeding has been surgically removed
7. Active or previous history of inflammatory bowel disease
8. History of moderate or severe renal impairment, with eGFR<45ml/min/1.73m2.
9. Previous invasive or noninvasive malignancy except:
9.1. DCIS where treatment consisted of resection alone.
9.2. Prostate cancer initially treated with prostatectomy and now being treated with salvage radiotherapy following a rise in PSA.
9.3. Cervical carcinoma in situ where treatment consisted of resection alone.
9.4. Basal cell carcinoma where treatment consisted of resection alone or radiotherapy.
9.5. Superficial bladder carcinoma where treatment consisted of resection alone.
9.6. Other cancers where the patient has been disease free for =15 years.
10. Any other physical condition which is associated with increased risk of aspirin related
morbidity or, in the opinion of the Investigator, makes the patient unsuitable for the trial, including but not limited to severe asthma, haemophilia and other bleeding diatheses, macular degeneration and patients with a high risk of mortality from another cause within the trial treatment period
11. Known glucose6phosphate dehydrogenase deficiency
12. Known lactose intolerance
13. LFTs greater than 1.5x the upper limit of normal unless agreed with TMG
14. Anticipated difficulties in complying with trial treatment or followup schedules
15. <16 years old
16. Participants in other treatment trials where this has not been agreed in advance by both trial teams
17. Pregnant or breast feeding, or intending to become pregnant or breast feed during the trial treatment period

Breast cohort exclusion criteria:
1. Metastatic or bilateral breast cancer.

Colorectal cohort exclusion criteria:
1. Proven (or clinically suspected) metastatic disease (patients who have undergone resection of liver metastases with clear margins and no residual metastatic disease are eligible)

Gastroesophageal cohort exclusion criteria:
1. Proven (or clinically suspected) metastatic disease.

Prostrate cohort participant criteria:
1. Biopsy proven or radiologically suspected nodal involvement, or distant metastases from prostate cancer
2. Adjuvant hormone therapy planned for >3 years
3. Bilateral orchidectomy

Recruitment start date

01/03/2015

Recruitment end date

28/02/2021

Locations

Countries of recruitment

United Kingdom

Trial participating centre

Medical Research Council Clinical Trials Unit (MRC CTU)
Aviation House 125 Kingsway
London
WC2B 6NH
United Kingdom

Sponsor information

Organisation

University College London

Sponsor details

Gower Street
London
WC1E 6BT
United Kingdom

Sponsor type

University/education

Website

Funders

Funder type

Government

Funder name

National Institute for Health Research

Alternative name(s)

NIHR

Funding Body Type

government organisation

Funding Body Subtype

Federal/National Government

Location

United Kingdom

Funder name

Cancer Research UK

Alternative name(s)

CRUK

Funding Body Type

private sector organisation

Funding Body Subtype

other non-profit

Location

United Kingdom

Results and Publications

Publication and dissemination plan

Not provided at time of registration

Intention to publish date

Participant level data

Not provided at time of registration

Results - basic reporting

Publication summary

Publication citations

Additional files

Editorial Notes