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

NCT03047837 | Terminated Phase 2

• 2 other identifiers: 27UCS20152015-004824-77
• Study Type: interventional
• Target: 160
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Tertiary Prevention in Colon Cancer

Keywords

Colorectal cancer; aspirin; metformin; chemoprevention

Outcome Measures

Primary Outcomes (1)

• NFκB

  It will be measured the change, defined as the difference between post- and pre-treatment levels, in NFκB expression in normal colonic tissue. The NFκB transcription factor family is composed of the p65, RelB, c-Rel, p105, andt p100 subunits, and activation of the NFκB 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 NFκB activity. The analysis of expression will be performed by semi quantitative assessment: NFκB 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 Outcomes (4)

• pS6K, p53, beta-catenin, PI3K

  1 year

• IL-6, CRP, VEGF and HOMA index

  1 year

• Gene expression levels

  1 year

• Metformin concentration

  1 Year

Study Arms (4)

Placebo

PLACEBO COMPARATOR

placebo Aspirin (1 tablet daily) + placebo Metformin (1 tablet BID) for 12 months

Other: Placebo

Metformin

EXPERIMENTAL

placebo Aspirin (1 tablet daily) + active Metformin (850 mg, 1 tablet BID), for 12 months

Drug: MET

Aspirin

EXPERIMENTAL

active Aspirin (100 mg, 1 tablet daily) + placebo Metformin (1 tablet BID), for 12 months

Drug: ASA

Apirin plus Metformin

EXPERIMENTAL

active Asprin (100 mg, 1 tablet daily) + active Metformin (850 mg, 1 tablet BID), for 12 months

Drug: ASA; Drug: MET

Interventions

ASA DRUG

Arm C (experimental arm) Treatment: active ASA + placebo MET Dose: 100 mg, 1 tablet daily + 1 tablet twice a day (BID) Duration: 12 months

Also known as: Cardioaspirin

Apirin plus Metformin; Aspirin

MET DRUG

Arm B (experimental arm) Treatment: placebo ASA + active MET Dose: 1 tablet daily+ 850 mg, 1 tablet twice a day (BID) Duration: 12 months

Also known as: Metformin

Apirin plus Metformin; Metformin

Placebo OTHER

Arm A (control arm) Treatment: placebo ASA + placebo MET Doses: 1 tablet daily +1 tablet twice a day (BID) Duration: 12 months

Placebo

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).

You may not qualify if:

• 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).
• 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.

Sponsors & Collaborators

• Ente Ospedaliero Ospedali Galliera: lead

Study Sites (1)

Medical Oncology Ente Ospedaliero Ospedali Galliera

Genova, 16128, Italy

Location

Related Publications (1)

• Petrera M, Paleari L, Clavarezza M, Puntoni M, Caviglia S, Briata IM, Oppezzi M, Mislej EM, Stabuc B, Gnant M, Bachleitner-Hofmann T, Roth W, Scherer D, Haefeli WE, Ulrich CM, DeCensi A. The ASAMET trial: a randomized, phase II, double-blind, placebo-controlled, multicenter, 2 x 2 factorial biomarker study of tertiary prevention with low-dose aspirin and metformin in stage I-III colorectal cancer patients. BMC Cancer. 2018 Dec 4;18(1):1210. doi: 10.1186/s12885-018-5126-7.

  PMID: 30514262 DERIVED

MeSH Terms

Conditions

Colorectal Neoplasms

Interventions

Metformin

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Intervention Hierarchy (Ancestors)

Biguanides; Guanidines; Amidines; Organic Chemicals

Study Officials

• Andrea De Censi, MD

  E.O. Ospedali Galliera

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: FACTORIAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: February 1, 2017
• First Posted: February 9, 2017
• Study Start: March 15, 2017
• Primary Completion: March 31, 2024
• Study Completion: March 31, 2024
• Last Updated: January 27, 2025

Record last verified: 2025-01

Data Sharing

• IPD Sharing: Will not share

Locations

IT (1)