ATTom study Design
ATTom – Adjuvant Tamoxifen Treatment offer more?
ATTom is a very large, uniquely simple randomised study of the effects of prolonging
adjuvant tamoxifen on the survival of patients with operable breast cancer
Breast carcinoma completely excised Any primary treatment At least 2 years prior tamoxifen treatment Clinically relapse free
Is further Tamoxifen
indicated at this time? Definitely Definitely
Patient is Reconsider
Eligible later UNCERTAIN
whether to continue or not
tamoxifen for a further 5
Exclusion Criteria: Eligibility Criteria:
Definite contraindications to tamoxifen are not Any woman who is clinically relapse free, and who
specified by the protocol, is currently taking tamoxifen can join the aTTom
but might include: study.
Intended or actual pregnancy or breastfeeding The patient is eligible if there are thought not to be
Significant endometrial hyperplasia any clear indications for or definite contraindications
Retinopathy against further tamoxifen, and hence substantial
Need for anti-coagulant therapy. uncertainty exists at to stop or continue treatment.
Serious toxicity (eg. Depression) thought due to
tamoxifen Women who have received any type of initial
or surgery who have received any other type of
Negligibly low risk of breast cancer death adjuvant treatment are eligible for aTTom. Women
Some major life threatening disease other than breast may have node positive or node negative disease, be
cancer (such that management of breast cancer is not pre or post-menopausal, and have ER positive or ER
the main concern) negative tumours, etc.
Low probability of treatment compliance (eg.
psychiatric disorders, or extreme old age).
SECRAB Study Design
SEquencing of Chemotherapy and Radiotherapy in Adjuvant Breast cancer
A large randomised clinical trial designed to determine the optimum sequencing of
chemotherapy and radiotherapy in the adjuvant treatment of early breast cancer
Women with early breast cancer having adjuvant chemotherapy
and radiotherapy following
conserving surgery or
Prescribe appropriate CT and RT regimens
Decide if a Boost dose will be given
Obtain informed consent
Sequential Schedule Synchronous Schedule
Chemotherapy followed Chemotherapy
Radiotherapy by Radiotherapy Chemotherapy
Annual follow-up for five years (relapse and survival status)
Histological diagnosis of invasive, unilateral breast carcinoma.
Wide local excision or mastectomy with macroscopic complete excision of clinically early stage
disease with no evidence of metastases.
There is a clear indication for both adjuvant chemotherapy and radiotherapy, or the patient has been
randomised to these treatments in another study.
The intended schedules can be given synchronously and the patient is suitable for either treatment
No prior chemotherapy (other than hormone manipulation).
No prior malignancy (except skin basal/squamous cell or in situ carcinoma).
No other medical or social contraindication to entry and follow-up.
DEVA – Study Design
Sequential Epirubicin & Docetaxel vs Epirubicin alone in postmenopausal primary breast cancer
Eligible patients Post-menopausal Node positive breast cancer No distant metastases Completely resected
EPIRUBICIN 50mg/m22 EPIRUBICIN 50mg/m Day 1 & Day 8 Day 1 and Day 8 6x cycles 4-weekly 3x cycles 4-weekly Followed by: 2 DOCETAXEL 100mg/m
3x 3-weekly cycles
*TAMOXIFEN (sequential vs concurrent)
Centres not partaking in
sequential vs concurrent
Sequential Concurrent Concurrent tamoxifen for Tamoxifen tamoxifen for 5 years for 5 years 5 years
Follow up prior to each course of chemotherapy, and months 9 & 12. Then
months 16, 20, 24, 30, 36, 42, 48, and annually thereafter
Eligibility Criteria: Postmenopausal, histologically proven node positive breast cancer
No evidence of metastases
WHO performance status 0 or 1 & Biochemistry within normal limits:
99/l or ANC?1.5 x 10/l 9Platelets ? 100 10/l
SCGOT, SGPT and alkaline phosphatase ? 1.5 x normal, serum Creatinine <1.5 x normal.
(for patients allocated to epirubicin followed by docetaxel, the LFTs should be checked again
prior to commencing treatment with docetaxel) No significant cardiac disease (ECG and/or LVEF by MUGA scan/echocardiography). Centres
should inform the Data centre of the type of assessment intended for all patients randomised
*For ER- & PgR- patients, tamoxifen treatment id according to discretion of the clinician.
FOCUS Study Design
Fluorouracil, Oxaliplatin and Irinotecan: Use and Sequencing
A randomised trial to assess the role of irinotecan and oxaliplatin in advanced colorectal
Eligible patient: advanced colorectal cancer, not previously Randomise treated with chemotherapy for metastatic disease
Plan A Plan B Plan C Plan D Plan E
MdG MdG IrMdG MdG OxMdG until
until until until until progression
progression progression progression progression
Second-line Second-line Second-line
single agent IrMdG OxMdG irinotecan
Upon progression, management at the clinician’s discretion, usually supportive care alone. If further
chemotherapy is to be used, use a non-crossover regimen. PVI 5FU + mitomycin is recommended
Abbreviations: MdG – Modified de Gramont
IrMdG – Modified de Gramont + irinotecan
OxMdG – Modified de Gramont + oxaliplatin
Eligibility Criteria: Exclusion Criteria:
Histologically confirmed adenocarcinoma of the colon or Concurrent uncontrolled medical illness, or other rectum current malignant disease likely to interfere with Inoperable metastatic or locoregional disease protocol treatments or comparisons No previous chemotherapy for established metastatic Partial or complete bowel obstruction disease (if adjuvant chemo was give previously, it may Age<18. No fixed upper age limit, use precaution in have included 5FU but not oxaliplatin or irinotecan, and selection of elderly patients must have been completed >6months prior to trial entry) Pre-existing neuropathy (>grade1) Measurable disease (RECIST classification) Chronic diarrhoea or inflammatory bowel disease 99WBC>4 x10/l, platelet count >150 x 10/l, Bilirubin Gilbert’s Syndrome or other congenital abnormality of <1.25 upper limit of normal(ULN) and ALP<5 x ULN biliary transport GFR>50ml/min Previous transplant surgery, requiring WHO PS 0, 1 or 2 immunosuppressive therapy (due to interaction of WOCBP negative pregnancy test & adequate contraceptive cyclosporin-A with irinotecan precautions Unable to comply with QoL assessment
VICTOR Study Design
VIOXX in Colorectal Cancer Therapy: definition of Optimal
Randomised, double blind, placebo-controlled study or Rofecoxib (VIOXX)
in colorectal cancer patients following potentially curative therapy
Patient fulfils eligibility criteria
2 years 5 years 2 years 5 years
Eligibility Criteria: Exclusion Criteria:
Histologically proven Dukes C (stage III: any T, N, Patients with active peptic ulceration or GI 1-2
M or B (stage II: T or , N, M) colorectal bleeding in the last year 0) 3400
carcinoma Past history of adverse reaction to NSAID eg. Patients must have undergone complete resection of Asthma, acute rhinitis, nasal polyps, angioneurotic the primary tumour without gross or microscopic oedema or urticaria evidence of residual disease Known sensitivity to VIOXX WHO PS 0 or 1 Long-term NSAID therapy (except low dose 99ANC?x 10aspirin) /l, platelets >100 x 10/l, Bilirubin
<18 years of age AST/ALT 1.5 x upper limit of normal,
Pregnancy or lactation GFR>30ml/min. Tests to be carried out ? 2 weeks
Previous malignancies other then adequately prior to randomisation
treated in situ carcinoma of the uterine cervix or Within 12 weeks of finishing potentially curative
basal or squamous cell carcinoma of the skin, therapy (surgery alone, or surgery + Radiotherapy
unless there has been a disease free interval for at +/- Chemotherapy
least 10 years
Inflammatory bowel disease
Severe congestive heart failure
GELCAPS Study Design
Genetic Lung Cancer Predisposition Study
Patients diagnosed with lung Partner of patient cancer (wherever possible)
Blood sample taken for
analysis at trial centre
All patients who have been diagnosed with lung cancer, irrespective of whether
the patient smokes are eligible. (Adenocarcinoma must be histologically proven
from bronchial biopsy or surgical resection)
NSCLC must be specified cell type eg. Squamous
Patients may enter the study at any time after diagnosis
The partner of the patient includes spouse, same sex partner or other
unrelated adult living long term in the same house as the patient.
The partner must not have developed a smoking related malignancy
Smoking and non-smoking partners are eligible for entry into the study
9At the time of sampling, the patient must have WBC at least 2x10/l. It is
not necessary to routinely check the partners’ WBC
It is vital for the success of GELCAPS that a group B partner is
recruited to GELCAPS wherever possible
MESO-1 Study Design
Randomised feasibility study of active symptom control with or without chemotherapy in the treatment of
patients with mesothelioma
Patient with diagnosis of mesothelioma
No further information is
Randomise required regarding this patient
ASC ASC + MVP ASC + N
Patients are followed up every 8 weeks until death.
QoL should be completed by every patient - prior to being informed of their allocated treatment
ASC: Active symptom control 222MVP:Mitomycin (8 mg/m), vinblastine (6mg/m) and cisplatin (50 mg/m) to be given every 21
days with a total of 4 cycles 2N: 6 weekly injections of vinorelbine (30 mg/m) followed by a 2-week interval before a further
course of 6 weekly injections
Microscopically and immunohistochemically confirmed malignant mesothelioma, including
epithelial and other histological types.
Any symptomatic pleural effusion treated and brought under control by drainage, pleurodesis
or pleurectomy before trial entry.
CT scan to be performed within a month prior to randomisation and, wherever possible, after
Patients who have undergone surgical resection of mesothelioma are eligible provided 2 CT
scans, 6 weeks apart; show stable or progressive disease which is assessable.
No previous chemotherapy for mesothelioma.
No other disease or previous malignancy likely to interfere with protocol treatments or
WHO status 0-2.
999/l, neutrophils>1.5x10/l, platelets>100x10/l, and there is no clinical evidence of infection.
Considered medically fit to receive chemotherapy.
Patient has completed QoL forms prior to being informed of treatment allocated.
MALCS Study Design
A population based case-control study of mesothelioma and lung cancer in
relation to occupation among British men and women under the age of 60
Mesothelioma & resected lung cancer patients aged under
Obtain informed consent
Telephone interview conducted by Institute of Cancer research
Lung sample obtained post
All mesothelioma & resected lung cancer patients aged 60 years, registered with a GP
Not to have worked outside the UK for longer then 1 year (except members of the Armed Forces, who will be included regardless of where they were stationed) this doesn’t include living abroad as a child.
Telephone owners (not ex-directory)
GP informed & permission sought for patients’ inclusion. Telephone interviews are conducted by researchers at the Institute of Cancer
Post mortem lung samples will be provided by relevant pathologist to trial centre & examined for fibre content
LU22 Study Design
Randomised trial of surgical resection with or without pre-operative
chemotherapy in patients with operable non-small cell lung cancer (NSCLC) or
First QoL form completed
Surgery Chemotherapy & surgery
MVP: Vinblastine 6mg/m
, and cisplatin 50mg/m at 3-week intervals for 3 cycles, 22
with Mitomycin 8 mg/2
MIC: Same as MVP but with ifosfamide 3g/m instead of vinblastine 2
NP: Vinorelbine (Navelbine) 30 mg/m on days 1 and 8 and cisplatin 80 mg.m on 22
day 1 at 3-week intervals for 3 cycles
Eligibility Criteria: Previously untreated NSCLC, microscopically proven from biopsy or cytology Tumour considered resectable by surgeon No evidence of distant metastases No contra-indication to chemotherapy or surgery No disease or previous malignancy likely to interfere with the protocol treatments or comparisons. Clinical and CT staging for all patients Mediastinoscopy for patients with possible N2 or T3N1 disease on CT scan. Then, only patients with pN0 or single-station nodal involvement should be considered.
POSH Study Design
Prospective Outcomes in Sporadic vs. Hereditary breast cancer
Patient is ?40 years old Invasive breast cancer
Obtain informed consent
Blood sample is taken & sent to Fresh tumour sample sent to trial centre for DNA analysis trial centre if patient has (before surgery if possible) strong family history
Family history questionnaire block sent temporarily to trial
completed centre if no fresh sample
Follow-up questionnaires at 6 and 12 months, then annually
Neither patients nor clinicians will be informed of patients’ BRCA status. Patients
who wish to have genetic counselling may be referred to:
Dr Fiona Douglas
Consultant Clinical Geneticist
Institute of Human Genetics
International Centre for Life
Newcastle upon Tyne
Tel 0191 2418725