A Randomized, 2x2 Factorial Design Biomarker Prevention Trial of Low-dose ASA and Metformin in Stage I-III Crc Patients

• Register: ClinicalTrials.gov
• Last refreshed on: 4 March 2024
• Main ID: NCT03047837
• Date of registration: 01/02/2017
• Prospective Registration: Yes
• Primary sponsor: Ente Ospedaliero Ospedali Galliera
• Public title: A Randomized, 2x2 Factorial Design Biomarker Prevention Trial of Low-dose ASA and Metformin in Stage I-III Crc Patients ASAMET
• Scientific title: A Randomized, Phase II, Double-blind, Placebo-controlled, Multicenter, 2x2 Factorial Design Biomarker Tertiary Prevention Trial of Low-dose Aspirin and Metformin in Stage I-III Colorectal Cancer Patients. The ASAMET Trial
• Date of first enrolment: March 15, 2017
• Target sample size: 160
• Recruitment status: Active, not recruiting
• URL: https://clinicaltrials.gov/ct2/show/NCT03047837
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Factorial Assignment. Primary purpose: Prevention. Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor).
• Phase: Phase 2

Countries of recruitment

Italy

Contacts

• Name: Andrea De Censi, MD
• Affiliation: E.O. Ospedali Galliera

Key inclusion & exclusion 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. Patients
with 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:

- Platelets = 100 x 10^9/L

- 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.

- 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).

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.

- Prior history of gastro-intestinal bleeding 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 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.



Age minimum: 18 Years
Age maximum: 80 Years
Gender: All

Health Condition(s) or Problem(s) studied

Tertiary Prevention in Colon Cancer

Intervention(s)

Drug: MET

Other: Placebo

Drug: ASA

Primary Outcome(s)

NF?B [Time Frame: 1 year]

Secondary Outcome(s)

pS6K, p53, beta-catenin, PI3K [Time Frame: 1 year]

Gene expression levels [Time Frame: 1 year]

Metformin concentration [Time Frame: 1 Year]

IL-6, CRP, VEGF and HOMA index [Time Frame: 1 year]

Secondary ID(s)

2015-004824-77

27UCS2015

Source(s) of Monetary Support

Please refer to primary and secondary sponsors