Surgical resected colorectal cancer (stage I-III) MedDRA version: 19.1 Level: SOC Classification code 10029104 Term: Neoplasms benign, malignant and unspecified (incl cysts and polyps) System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Trade Name: CARDIOASPIRIN - 100 MG COMPRESSE GASTRORESISTENTI30 COMPRESSE
Product Name: Aspirina
Product Code: B01AC06
Pharmaceutical Form: Tablet
Pharmaceutical form of the placebo: Tablet
Route of a
Sponsors
ENTE OSPEDALIERO OSPEDALI GALLIERA
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Patients aged > 18 and = 80 years. • Patients with completely resected stage I, II, or III primary colorectal cancer within 24 months prior to randomization, regardless of (neo-)adjuvant chemotherapy. Patientswith pT1 CRC treated with endoscopic polypectomy. • Adjuvant chemotherapy and (neo)adjuvant radiotherapy terminated at least 3 months before randomization. • ECOG performance status = 1. • Satisfactory hematological and biochemical functions: o Platelets = 100 x 10^9/L o Creatinine clearance estimated with the Cockcroft - Gault formula = 60 mL/min. Patients with Gault formula = 45-59 = ml/min are eligible but they will receive a single (evening) tablet of MET, 850 mg. o AST and ALT = 2.5 times ULN. • Females of childbearing potential/males with partners of childbearing potential participating in the study are to use effective methods of birth control during study participation. Female participants must provide a pregnancy test, according to local national guidelines. • Able to understand and sign an informed consent (or have a legal representative who is able and willing to do so). Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 100 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 60
Exclusion criteria
Exclusion criteria: Patients who are not able to undergo colonoscopy. • Patients who are allergic or intolerant to ibuprofen or naproxen, or who have MET-, or ASA-, or salicylate intolerance or more generalized drug intolerance to non-steroidal anti-inflammatory drugs (NSAIDs). • Any serious medical condition, laboratory abnormality, or psychiatric illness that would prevent the patient from signing or participating in the study and/or comply with study procedures. • Chronic treatment with ASA or other NSAIDs or MET or patients who are on current long term treatment (= 4 consecutive weeks) with ASA, NSAID or COX -2 inhibitors or MET. • Diabetic patients on drug treatment are excluded. • Anticoagulant therapy (dicumarol, heparin, fondaparinux, apixaban, dabigatran etexilate, rivaroxaban) or active current treatment with antiplatelet agents (e.g. off-study ASA, clopidogrel, prasugrel, ticagrelor, or ticlopidine). • Any other invasive malignancies (with the exclusion of basal cell carcinoma or cutaneous squamous cell carcinoma) diagnosed during the last 5 years before randomization. • Past history of any other invasive CRC than the one the patient is currently being treated for • Alcohol or drug abuse, defined according to Investigators discretion. • Prior history of gastro-intestinal bleeding to ASA or hemorrhagic diathesis (e.g. hemophilia). • Erosive-ulcerative lesions in the gastrointestinal tract • History of erosive GERD or active erosive GERD on gastroscopy. • Concomitant corticosteroid treatment. • Known hypersensitivity or intolerance to MET or ASA or NSAID. • Known deficiency of glucose-6-phosphate dehydrogenase (G6PD). • Treatment with another investigational drug < 28 days prior to study entry. • Concurrent participation in a clinical trial with the same endpoints. • History of hemorrhagic stroke. • Lynch Syndrome (HNPCC). • Crohn's disease (CD) and Ulcerative Colitis (UC). • Pregnant or lactating females. • History of lactic acidosis. • Liver dysfunction including chronic active hepatitis and cirrhosis not compensated. • History of vitamin B12 deficiency or megaloblastic anemia. • Uncontrolled coronary syndrome or symptomatic congestive heart failure (e.g. Class III or IV New York Heart Association's Functional Classification). • Inability or unwillingness to swallow tablets.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Timepoint(s) of evaluation of this end point: 12 months;Main Objective: To test the synergistic effect of the combined treatment with low dose ASA plus MET given for 1 year to reduce the expression of NF?B (primary endpoint) in unaffected colonic tissue in patients with removed CRC. ;Primary end point(s): To test the synergistic effect of the combined treatment with low dose ASA plus MET given for 1 year to reduce the expression of NF?B (primary endpoint) in unaffected colonic tissue in patients with removed CRC.;Secondary Objective: To test the effect of treatment with ASA and MET, in combination and independently, on the following secondary endpoints: •The change in IHC expression levels of pS6K, p53, beta-catenin, PI3K •The change in the circulating biomarkers IL-6, CRP, VEGF and HOMA index •The gene expression levels of candidate genes , pathways and genome-wide expression profile in colon unaffected biopsy tissue. To define the blood and tissue drug levels of metformin, • To genetically characterize the primary colorectal carcinomas using NGS and determine their association with treatment response. •To study the treatment tolerability comparing incidence and grade of toxicities among arms •To study the serum concentrations of TBx as a biomarker of treatment adherence,to be correlated with biomarker modulation and toxicity. •To evaluate the effect of treatment on psychological variables and cancer related fatigue. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): To test the effect of treatment with ASA and MET, in combination and independently, on the following secondary endpoints: •The change in IHC expression levels of pS6K, p53, beta-catenin, PI3K •The change in the circulating biomarkers IL-6, CRP, VEGF and HOMA index •The gene expression levels of candidate genes , pathways and genome-wide expression profile in colon unaffected biopsy tissue. To define the blood and tissue drug levels of metformin, 3. To genetically characterize the primary colorectal carcinomas using NGS and determine their association with treatment response. 4. To study the treatment tolerability comparing incidence and grade of toxicities among arms 5. To study the serum concentrations of TBx as a biomarker of treatment adherence,to be correlated with biomarker modulation and toxicity. 6. To evaluate the effect of treatment on psychological variables and cancer related fatigue.;Timepoint(s) of evaluation of this end point: T0 (basal), T1 (12 months of treatment) | — |
Countries
Austria, Italy, Slovenia
Contacts
Public ContactUfficio del Coordinatore Scientific
Ente Ospedaliero Ospedali Galliera
Outcome results
None listed