DESIGN DE L`ETUDE 185 patients (123 vs 62) seront inclus dans

Etude SAKK 41/13-Aspirin, v1.0 dngn 02.03.2016
ADJUVANT ASPIRIN TREATMENT IN PIK3CA MUTATED COLON CANCER PATIENTS.
A RANDOMIZED, DOUBLE-BLINDED, PLACEBO-CONTROLLED, PHASE III TRIAL
“Etude : SAKK 41/13-Aspirin”
Sponsor : SAKK
CONTACTS AUX HUG : Unité de recherche en Onco-Hématologie de la Fondation DFDL
 Coordinatrice de l’étude : Mme Christelle Trembleau, 079 553 53 91
 Investigateur responsable: Prof. Arnaud Roth, 079553 23 95
 Secrétariat: Mme Florence Marti-Klay, 022 372 29 01
DESIGN DE L’ETUDE
185 patients (123 vs 62) seront inclus dans cette étude et randomisés (2:1), selon le
schéma suivant :
Randomization 2:1
Stage II or III colon cancer
PIK3CA testing
Mutated PIK3CA
Aspirin 100mg
daily for 3 years
Standard chemo if indicated
Placebo
daily for 3 years
Standard chemo if indicated
Follow-up
up to 10 years from the date of surgery

Etude SAKK 41/13-Aspirin, v1.0 dngn 02.03.2016
OBJECTIF DE L'ETUDE
L’objectif de cette étude est de démontrer le bénéfice statistiquement significatif
d’une survie sans maladie chez des patients atteints d’un cancer du côlon de stade II
et III PIK3CA muté chez prenant de l’aspirine adjuvant quotidiennement pendant 3
ans.
CRITERES D’ELIGIBILITE
#
INCLUSION CRITERIA
1
Written informed consent according to ICH/GCP regulations before inclusion and prior to any trial-
related investigations.
2
Histologically confirmed diagnosis of adenocarcinoma of the colon
3
Stage II (pT3/T4 N0 cM0) or stage III (pTx pN+ cM0) colon cancer
4
Availability of cancer tissue for central molecular testing
5
Presence of predefined, activating PIK3CA mutation in exons 9 or 20 (centrally assessed, see
section 17)
6
Complete resection of the primary tumor (R0) within 10 weeks maximum before registration
7
WHO performance status 0-2 (see Appendix 3)
8
Age between 18–80 years
9
Adequate hematological values: hemoglobin ≥ 80 g/L, platelets ≥ 50 x 109/L
10
Calculated creatinine clearance > 30 mL/min, according to the formula of Cockcroft-Gault
11
Women with child-bearing potential are using effective contraception (see 9.6), are not pregnant or
lactating and agree not to become pregnant during trial treatment. A negative pregnancy test
before inclusion (within 7 days) into the trial is required for all women with child-bearing potential
#
EXCLUSION CRITERIA
1
Previous or concomitant malignancy within 3 years of registration, except for adequately treated
cervical carcinoma in situ or localized non-melanoma skin cancer
2
Multiple adenocarcinomas of the colon
3
Rectal cancer (defined as distance from anal verge to proximal/oral tumor edge ≤15 cm)
4
Severe or uncontrolled cardiovascular disease (congestive heart failure NYHA III or IV (see
Appendix 4), unstable angina pectoris, history of myocardial infarction) within three months prior to
registration
5
Systemic rheumatic diseases or degenerative disorders affecting the musculoskeletal system with
a relevant risk of requiring treatment with NSAIDs in the future
6
Comorbidities that require regular (i.e. more than 3x per month, any dose) intake of acetylsalicylic
acid or other NSAIDs or COX-2 inhibitors
7
Clinically relevant upper gastrointestinal bleeding within 12 months prior to registration
8
Presence of any bleeding disorder that is an absolute contraindication to the use of aspirin
9
Any serious underlying medical condition, at the judgment of the investigator, which could impair
the ability of the patient to participate in the trial (e.g. uncontrolled infection, active autoimmune
disease, uncontrolled diabetes)
10
Concurrent treatment with other experimental drugs or treatment in an interventional clinical trial
within 30 days prior to trial entry. Concomitant use of adjuvant chemotherapy for stage III and high
risk stage II colon cancer according to international treatment
guidelines is allowed (chemotherapy regimens include intravenous 5-fluorouracil or oral
capecitabine either alone or in combination with intravenous oxaliplatin)
11
Psychiatric disorder precluding understanding of trial information, giving informed consent or
interfering with compliance for oral drug intake
12
Any familial, sociological or geographical condition potentially hampering proper staging and
compliance with the trial protocol
13
Known or suspected hypersensitivity to any component of the trial drug or any agent given in
association with this trial
14
Any concomitant drugs contraindicated for use with the trial drug according to the approved
product information