Adjuvant Aspirin Treatment for Colon Cancer Patients

NCT ID: NCT02467582

Last Updated: 2025-05-16

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE3
• Total Enrollment: 1040 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-06-09
• Study Completion Date: 2023-09-14

Brief Summary

Following complete resection of their primary tumor, potentially eligible stage II or stage III colon cancer patients will undergo central PIK3CA testing. Patients with somatic mutations will be 2:1 randomized to daily aspirin 100 mg versus placebo for a a maximum of 3 years or until disease recurrence, patient death or withdrawal of consent, whichever occurs first. Patients will be followed up for at least 3 years from the date of surgery.

The intake of aspirin or placebo is independent of adjuvant chemotherapy, and does not impact on the indication to give (or not to give) adjuvant chemotherapy.

Detailed Description

Colorectal cancer is the third most common malignancy for both women and men and is responsible for almost 10% of all cancer death. Despite complete removal of the tumor and use of adjuvant chemotherapy, up to 25% of patients with stage II colon cancer and up to 50% of patients with stage III disease will suffer from recurrences, which is associated with poor prognosis.

Several retrospective observations have documented a favorable effect of long-term intake of oral aspirin for the prevention of colorectal cancer in different clinical situations. Regular intake of aspirin after the diagnosis of colorectal cancer may also be associated with a lower risk of colorectal cancer-specific and overall mortality. Two recent publications in prestigious medical journals provided retrospective evidence that patients with PIK3CA-mutated colon cancer may derive a very substantial benefit from daily oral aspirin. Both analyses showed a roughly 85% reduction of the risk for tumor relapse compared to patients who did not take aspirin. However, a potential selection bias in these retrospective analyses cannot be excluded with certainty. These extremely interesting and intriguing findings must be confirmed in a randomized controlled trial to potentially change clinical practice.

The trial objective is to demonstrate a statistically significant and clinically relevant disease-free survival benefit in stage II and III PIK3CA mutated colon cancer patients taking daily adjuvant aspirin for 3 years.

Patients with resected colon cancer stage II or stage III bearing somatic mutations in exon 9 or 20 of PIK3CA will be 2:1 randomized to daily adjuvant aspirin 100 mg versus placebo for a maximum of 3 years or until disease recurrence, patient death or withdrawal of consent, whichever occurs first. Patients will be followed up for at least 3 years from the date of surgery. The intake of aspirin or placebo is independent of adjuvant chemotherapy, and does not impact on the indication to give (or not to give) adjuvant chemotherapy.

Conditions

Colon Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

Aspirin 100 mg

Asprin 100 mg daily for maximum 3 years standard chemo if indicated

Group Type: EXPERIMENTAL

Aspirin

Intervention Type: DRUG

Aspirin 100 mg daily

Placebo

Placebo daily for maximum 3 years standard chemo if indicated

Group Type: ACTIVE_COMPARATOR

Placebo

Intervention Type: DRUG

Placebo

Interventions

Aspirin

Aspirin 100 mg daily

Intervention Type: DRUG

Placebo

Placebo

Intervention Type: DRUG

Other Intervention Names

acetylsalicylic acid

Eligibility Criteria

Inclusion Criteria

• Written informed consent according to ICH/GCP regulations before inclusion and prior to any trial-related investigations.
• Histologically confirmed diagnosis of adenocarcinoma of the colon.
• Stage II (pT3/T4 N0 cM0) or stage III (pTx pN+ cM0) colon cancer.
• Availability of cancer tissue for central molecular testing.
• Presence of predefined, activating PIK3CA mutation in exons 9 or 20 (centrally assessed).
• Complete resection of the primary tumor (R0) within 14 weeks maximum before registration.
• WHO performance status 0-2.
• Age between 18-80 years.
• Adequate hematological values: hemoglobin ≥ 80 g/L, platelets ≥ 50 x 109/L.
• Adequate hepatic function: total bilirubin ≤1.5xULN, AST ≤2.5xULN, ALT ≤2.5xULN, AP ≤2.5xULN.
• Calculated creatinine clearance > 30 mL/min, according to the formula of Cockcroft-Gault.
• Women with child-bearing potential are using effective contraception, 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

• Previous or concomitant malignancy within 3 years of registration, except for adequately treated cervical carcinoma in situ or localized non-melanoma skin cancer.
• Multiple adenocarcinomas of the colon.
• Rectal cancer (defined as distance from anal verge to proximal/oral tumor edge ≤15 cm).
• Severe or uncontrolled cardiovascular disease (congestive heart failure NYHA III or IV, unstable angina pectoris, history of myocardial infarction) within three months prior to registration.
• Systemic rheumatic diseases or degenerative disorders affecting the musculoskeletal system with a relevant risk of requiring treatment with NSAIDs in the future.
• Comorbidities that require regular (i.e. more than 3x per month, any dose) intake of acetylsalicylic acid or other NSAIDs or COX-2 inhibitors.
• Clinically relevant upper gastro-intestinal bleeding within 12 months prior to registration.
• Presence of any bleeding disorder that is an absolute contraindication to the use of aspirin.
• General tendency to hypersensitivity and history of asthma triggered by salicylates or substances with a similar mechanism of action, and non-steroidal anti-inflammatory drugs in particular
• 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).
• 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).
• Psychiatric disorder precluding understanding of trial information, giving informed consent or interfering with compliance for oral drug intake.
• Any familial, sociological or geographical condition potentially hampering proper staging and compliance with the trial protocol.
• Known or suspected hypersensitivity to any component of the trial drug or any agent given in association with this trial.
• Known galactose-1-phosphate uridyl transferase deficiency, UDP galactose 4 epimerase deficiency, galactokinase deficiency, orFanconi-Bickel syndrome, congenital lactase deficiency,or glucose-galactose malabsorption (due to the lactose-containing placebo).
• Any concomitant drugs contraindicated for use with the trial drug according to the approved product information.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

European Organisation for Research and Treatment of Cancer - EORTC

NETWORK

Sponsor Role: collaborator

Central European Society for Anticancer Drug Research

OTHER

Sponsor Role: collaborator

Swiss Cancer Institute

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Ulrich Güller, Prof

Role: STUDY_CHAIR

Spital STS AG Thun

Locations

Hopital Universitaire Brugmann

Brussels, , Belgium

Universitair Ziekenhuis Brussel

Brussels, , Belgium

Hôpital de Jolimont

Haine-Saint-Paul, , Belgium

CHC - Clinique Saint-Joseph

Liège, , Belgium

Az Damiaan

Ostend, , Belgium

AZ Turnhout - Campus Sint-Elisabeth

Turnhout, , Belgium

Spandau Vivantes Klinikum

Berlin, , Germany

Fürst-Stirum-Klinik Bruchsal

Bruchsal, , Germany

pioh KÖLN

Cologne, , Germany

Universitätsklinikum Dresden

Dresden, , Germany

Kliniken Essen Mitte

Essen, , Germany

pioh Frechen

Frechen, , Germany

Praxis und Tagesklinik - Medizinische Management GmbH

Friedrichshafen, , Germany

Überörtliche Gemeinschaftspraxis - Schwerpunkt Haematologie, internistische Onkologie & Palliativmedizin

Hamburg, , Germany

Universitätsklinikum Hamburg-Eppendorf

Hamburg, , Germany

Medizinische Hochschule Hannover

Hanover, , Germany

Onkologische Schwerpunktpraxis Heidelberg

Heidelberg, , Germany

Onkologie UnterEms

Leer, , Germany

Klinikum Ludwigsburg

Ludwigsburg, , Germany

Universitätsmedizin Mannheim

Mannheim, , Germany

Kliniken Maria Hilf GmbH - Krankenhaus St. Franziskus

Mönchengladbach, , Germany

Medizinische Klinik und Poliklinik III - Universitätsklinik

München, , Germany

Klinikum Nuernberg

Nuremberg, , Germany

Pi.Tri-Studien GmbH

Offenburg, , Germany

CaritasKlinikum Saarbrücken

Saarbrücken, , Germany

Marienhospital

Stuttgart, , Germany

Klinik für Innere Medizin I

Ulm, , Germany

Medizinische Studiengesellschaft NORD-WEST GmbH - Praxis Aurich

Westerstede, , Germany

Medizinische Studiengesellschaft NORD-WEST GmbH

Westerstede, , Germany

St. László Teaching Hospital

Budapest, , Hungary

Kantonsspital Aarau

Aarau, , Switzerland

Kantonsspital Baden

Baden, , Switzerland

Universitätsspital Basel

Basel, , Switzerland

St. Claraspital Basel

Basel, , Switzerland

IOSI, Ospedale San Giovanni

Bellinzona, , Switzerland

Klinik Engeried / Oncocare

Bern, , Switzerland

Inselspital Bern

Bern, , Switzerland

Spitalzentrum Biel

Biel, , Switzerland

Spitalzentrum Oberwallis

Brig, , Switzerland

Kantonsspital Graubünden

Chur, , Switzerland

HFR-Hôpital cantonal

Fribourg, , Switzerland

CCAC Fribourg

Fribourg, , Switzerland

Hopitaux Universitaires de Geneve

Geneva, , Switzerland

Clinique de Genolier

Genolier, , Switzerland

CCAC Lausanne

Lausanne, , Switzerland

Centre Hospitalier Universitaire Vaudois

Lausanne, , Switzerland

Kantonsspital Liestal

Liestal, , Switzerland

Kantonsspital Luzern

Lucerne, , Switzerland

Clinica Luganese

Lugano, , Switzerland

Onkologie Zentrum Spital Männedorf

Manno, , Switzerland

Spital Thurgau

Münsterlingen, , Switzerland

Hôpital de Pourtalès

Neuchâtel, , Switzerland

Kantonsspital Olten

Olten, , Switzerland

Kantonsspital St. Gallen

Sankt Gallen, , Switzerland

Spital Limmattal

Schlieren, , Switzerland

Hôpital du Valais Sion

Sion, , Switzerland

Bürgerspital Solothurn - Onkologiezentrum

Solothurn, , Switzerland

SpitalSTS AG Simmental-Thun-Saanenland

Thun, , Switzerland

Kantonsspital Winterthur

Winterthur, , Switzerland

Stadtspital Zürich Triemli

Zurich, , Switzerland

Countries

Belgium; Germany; Hungary; Switzerland

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

SNCTP000001339

Identifier Type: REGISTRY

Identifier Source: secondary_id

2015-001482-57

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

SAKK 41/13 - Aspirin

Identifier Type: -

Identifier Source: org_study_id