Adjuvant Aspirin Treatment for Colon Cancer Patients

Colon Cancer Clinical Trial

Official title:

Adjuvant Aspirin Treatment in PIK3CA Mutated Colon Cancer Patients. A Randomized, Double-blinded, Placebo-controlled, Phase III Trial

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT02467582
• Other study ID #: SAKK 41/13 - Aspirin
• Secondary ID: SNCTP00000133920
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: June 9, 2016
• Est. completion date: December 2024

Study information

• Verified date: January 2024
• Source: Swiss Group for Clinical Cancer Research
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 185
• Est. completion date: December 2024
• Est. primary completion date: September 14, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Colon Cancer
• Colonic Neoplasms

Intervention

Drug:
• Aspirin
Aspirin 100 mg daily
• Placebo
Placebo

Locations

Country	Name	City	State
Belgium	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	Oostende
Belgium	AZ Turnhout - Campus Sint-Elisabeth	Turnhout
Germany	Spandau Vivantes Klinikum	Berlin
Germany	Fürst-Stirum-Klinik Bruchsal	Bruchsal
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	Hannover
Germany	Onkologische Schwerpunktpraxis Heidelberg	Heidelberg
Germany	pioh KÖLN	Köln
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	Nuernberg
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	Westerstede
Germany	Medizinische Studiengesellschaft NORD-WEST GmbH - Praxis Aurich	Westerstede
Hungary	St. László Teaching Hospital	Budapest
Switzerland	Kantonsspital Baden	Baden
Switzerland	St. Claraspital Basel	Basel
Switzerland	Universitätsspital Basel	Basel
Switzerland	IOSI, Ospedale San Giovanni	Bellinzona
Switzerland	Inselspital Bern	Bern
Switzerland	Klinik Engeried / Oncocare	Bern
Switzerland	Spitalzentrum Oberwallis	Brig
Switzerland	Kantonsspital Graubünden	Chur
Switzerland	CCAC Fribourg	Fribourg
Switzerland	HFR-Hôpital cantonal	Fribourg
Switzerland	Hopitaux Universitaires de Geneve	Genève 14
Switzerland	Kantonsspital Liestal	Liestal
Switzerland	Clinica Luganese	Lugano
Switzerland	Kantonsspital Luzern	Luzern
Switzerland	Onkologie Zentrum Spital Männedorf	Manno
Switzerland	Spital Thurgau	Munsterlingen
Switzerland	Hôpital de Pourtalès	Neuchâtel
Switzerland	Hôpital du Valais Sion	Sion
Switzerland	Kantonsspital St. Gallen	St. Gallen
Switzerland	SpitalSTS AG Simmental-Thun-Saanenland	Thun
Switzerland	Kantonsspital Winterthur	Winterthur
Switzerland	Stadtspital Zürich Triemli	Zurich

Sponsors (3)

Lead Sponsor	Collaborator
Swiss Group for Clinical Cancer Research	Central European Society for Anticancer Drug Research, European Organisation for Research and Treatment of Cancer - EORTC

Countries where clinical trial is conducted

Belgium,  Germany,  Hungary,  Switzerland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Disease-free survival (DFS)		at 5 years after first patient in.
Secondary	Time to recurrence (TTR)		at 5 years after first patient in.
Secondary	Overall survival (OS)		at 5 years after first patient in and trial termination (7.5 years after first patient in)
Secondary	Cancer-specific survival (CSS)		at 5 years after first patient in and trial termination (7.5 years after first patient in).
Secondary	Adverse events (AEs)		at 5 years after first patient in.