Tertiary Prevention in Colon Cancer Clinical Trial
— ASAMETOfficial 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
| Verified date | February 2024 |
| Source | Ente Ospedaliero Ospedali Galliera |
| Contact | n/a |
| Is FDA regulated | No |
| Health authority | |
| Study type | Interventional |
It has been shown that Aspirin (ASA) as well as Metformin (Met) can inhibit the incidence and mortality of colorectal cancer (CRC). In this randomized, placebo controlled clinical trial we compare the effect of these two drugs alone and their combination to prevent recurrent CRC after surgery.
| Status | Active, not recruiting |
| Enrollment | 160 |
| Est. completion date | March 31, 2024 |
| Est. primary completion date | March 31, 2024 |
| Accepts healthy volunteers | No |
| Gender | All |
| Age group | 18 Years to 80 Years |
| Eligibility | 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. |
| Country | Name | City | State |
|---|---|---|---|
| Italy | Medical Oncology Ente Ospedaliero Ospedali Galliera | Genova |
| Lead Sponsor | Collaborator |
|---|---|
| Ente Ospedaliero Ospedali Galliera |
Italy,
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Primary | NF?B | It will be measured the change, defined as the difference between post- and pre-treatment levels, in NF?B expression in normal colonic tissue. The NF?B transcription factor family is composed of the p65, RelB, c-Rel, p105, andt p100 subunits, and activation of the NF?B pathway is defined by the nuclear translocation of the p65 subunit. Therefore, cytoplasmic and nuclear localization of p65 will be immunohistochemically assessed as an indicator of NF?B activity. The analysis of expression will be performed by semi quantitative assessment: NF?B expression will be measured primarily as the percentage of positive nuclear areas for NFkB over the total nuclear areas in 10 section fields. | 1 year | |
| Secondary | pS6K, p53, beta-catenin, PI3K | It will be measured the change (defined as above) in IHC expression levels of pS6K, p53, beta-catenin, PI3K (from colon unaffected biopsy specimen). These biomarkers will be measured as described above for NF?B. | 1 year | |
| Secondary | IL-6, CRP, VEGF and HOMA index | The change in circulating biomarkers IL-6, CRP, VEGF and HOMA index[homeostasis model assessment (fasting blood glucose (mmol/L)*insulin (mU/L))/22.5] will be measured in plasma and serum at two time points, pre- and post-intervention, using monoclonal ELISA kits. | 1 year | |
| Secondary | Gene expression levels | Gene expression levels of candidate genes and pathways, in normal colonic tissue, will be measured on a genome-wide basis using Illumina HumanHT-12 Expression BeadChips targeting more than 47,000 transcripts including known splice variants across the human transcriptome. | 1 year | |
| Secondary | Metformin concentration | The blood and tissue MET levels will be measured. LC-MS/MS system will be used for the drug level determinations to be correlated with biomarker modulation and toxicity | 1 Year |