Adjuvant Aspirin Treatment for Colon Cancer Patients

Sponsor

Swiss Group for Clinical Cancer Research (Other)

Overall Status

Active, not recruiting

CT.gov ID

NCT02467582

Collaborator

European Organisation for Research and Treatment of Cancer - EORTC (Other), Central European Society for Anticancer Drug Research (Other)

185

Enrollment

Locations

Arms

101.7

Anticipated Duration (Months)

3.6

Patients Per Site

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Colon Cancer	Drug: Aspirin Drug: Placebo	Phase 3

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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

185 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Triple (Participant, Care Provider, Investigator)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Jun 9, 2016

Anticipated Primary Completion Date :

Dec 1, 2024

Anticipated Study Completion Date :

Dec 1, 2024

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Aspirin 100 mg Asprin 100 mg daily for maximum 3 years standard chemo if indicated	Drug: Aspirin Aspirin 100 mg daily Other Names: acetylsalicylic acid
Active Comparator: Placebo Placebo daily for maximum 3 years standard chemo if indicated	Drug: Placebo Placebo

Arm

Intervention/Treatment

Experimental: Aspirin 100 mg

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

Drug: Aspirin

Aspirin 100 mg daily

Other Names:

acetylsalicylic acid

Active Comparator: Placebo

Placebo daily for maximum 3 years standard chemo if indicated

Drug: Placebo

Placebo

Outcome Measures

Primary Outcome Measures

Disease-free survival (DFS) [at 5 years after first patient in.]

Secondary Outcome Measures

Time to recurrence (TTR) [at 5 years after first patient in.]
Overall survival (OS) [at 5 years after first patient in and trial termination (7.5 years after first patient in)]
Cancer-specific survival (CSS) [at 5 years after first patient in and trial termination (7.5 years after first patient in).]
Adverse events (AEs) [at 5 years after first patient in.]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.

Contacts and Locations

Locations

	Site	City	Country	Postal Code
1	Hopital Universitaire Brugmann	Brussels	Belgium	1020
2	Universitair Ziekenhuis Brussel	Brussels	Belgium	1090
3	Hôpital de Jolimont	Haine-Saint-Paul	Belgium	7100
4	CHC - Clinique Saint-Joseph	Liège	Belgium	4000
5	Az Damiaan	Oostende	Belgium	8400
6	AZ Turnhout - Campus Sint-Elisabeth	Turnhout	Belgium	2300
7	Spandau Vivantes Klinikum	Berlin	Germany	13585
8	Fürst-Stirum-Klinik Bruchsal	Bruchsal	Germany	76646
9	Universitätsklinikum Dresden	Dresden	Germany	01307
10	Kliniken Essen Mitte	Essen	Germany	45136
11	pioh Frechen	Frechen	Germany	50226
12	Praxis und Tagesklinik - Medizinische Management GmbH	Friedrichshafen	Germany	88045
13	Überörtliche Gemeinschaftspraxis - Schwerpunkt Haematologie, internistische Onkologie & Palliativmedizin	Hamburg	Germany	20259
14	Universitätsklinikum Hamburg-Eppendorf	Hamburg	Germany
15	Medizinische Hochschule Hannover	Hannover	Germany	30625
16	Onkologische Schwerpunktpraxis Heidelberg	Heidelberg	Germany	69115
17	pioh KÖLN	Köln	Germany	50674
18	Onkologie UnterEms	Leer	Germany	26789
19	Klinikum Ludwigsburg	Ludwigsburg	Germany	71640
20	Universitätsmedizin Mannheim	Mannheim	Germany	68135
21	Kliniken Maria Hilf GmbH - Krankenhaus St. Franziskus	Mönchengladbach	Germany	41063
22	Medizinische Klinik und Poliklinik III - Universitätsklinik	München	Germany	83177
23	Klinikum Nuernberg	Nuernberg	Germany	90419
24	Pi.Tri-Studien GmbH	Offenburg	Germany	77654
25	CaritasKlinikum Saarbrücken	Saarbrücken	Germany	66113
26	Marienhospital	Stuttgart	Germany	70199
27	Klinik für Innere Medizin I	Ulm	Germany	89081
28	Medizinische Studiengesellschaft NORD-WEST GmbH - Praxis Aurich	Westerstede	Germany	26655
29	Medizinische Studiengesellschaft NORD-WEST GmbH	Westerstede	Germany	26655
30	St. László Teaching Hospital	Budapest	Hungary	H - 1097
31	Kantonsspital Baden	Baden	Switzerland	5404
32	Universitätsspital Basel	Basel	Switzerland	4031
33	St. Claraspital Basel	Basel	Switzerland	4058
34	IOSI, Ospedale San Giovanni	Bellinzona	Switzerland	6500
35	Klinik Engeried / Oncocare	Bern	Switzerland	3012
36	Inselspital Bern	Bern	Switzerland	CH-3010
37	Spitalzentrum Oberwallis	Brig	Switzerland	3900
38	Kantonsspital Graubünden	Chur	Switzerland	7000
39	HFR-Hôpital cantonal	Fribourg	Switzerland	1708
40	CCAC Fribourg	Fribourg	Switzerland
41	Hopitaux Universitaires de Geneve	Genève 14	Switzerland	1211
42	Kantonsspital Liestal	Liestal	Switzerland	4410
43	Clinica Luganese	Lugano	Switzerland	6900
44	Kantonsspital Luzern	Luzern	Switzerland	6000
45	Onkologie Zentrum Spital Männedorf	Manno	Switzerland	8708
46	Spital Thurgau	Munsterlingen	Switzerland	8596
47	Hôpital de Pourtalès	Neuchâtel	Switzerland
48	Hôpital du Valais Sion	Sion	Switzerland	1951
49	Kantonsspital St. Gallen	St. Gallen	Switzerland	9007
50	SpitalSTS AG Simmental-Thun-Saanenland	Thun	Switzerland	3600
51	Kantonsspital Winterthur	Winterthur	Switzerland	CH-8400
52	Stadtspital Zürich Triemli	Zurich	Switzerland	CH-8063