Clinical Trials /

Adjuvant Aspirin Treatment for Colon Cancer Patients

NCT02467582

Description:

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 total of 3 years or until disease recurrence, patient death or withdrawal of consent, whichever occurs first. Patients will be followed up for 10 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.

Related Conditions:
  • Colon Adenocarcinoma
Recruiting Status:

Recruiting

Phase:

Phase 3

Trial Eligibility

Document

Title

  • Brief Title: Adjuvant Aspirin Treatment for Colon Cancer Patients
  • Official Title: Adjuvant Aspirin Treatment in PIK3CA Mutated Colon Cancer Patients. A Randomized, Double-blinded, Placebo-controlled, Phase III Trial

Clinical Trial IDs

  • ORG STUDY ID: SAKK 41/13 - Aspirin
  • SECONDARY ID: SNCTP000001339
  • SECONDARY ID: 2015-001482-57
  • NCT ID: NCT02467582

Conditions

  • Colon Cancer

Interventions

DrugSynonymsArms
Aspirinacetylsalicylic acidAspirin 100 mg
PlaceboPlacebo

Purpose

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 total of 3 years or until disease recurrence, patient death or withdrawal of consent, whichever occurs first. Patients will be followed up for 10 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
      total of 3 years or until disease recurrence, patient death or withdrawal of consent,
      whichever occurs first. Patients will be followed up for up to 10 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.
    

Trial Arms

NameTypeDescriptionInterventions
Aspirin 100 mgExperimentalAsprin 100 mg daily for 3 years standard chemo if indicated
  • Aspirin
PlaceboActive ComparatorPlacebo daily for 3 years standard chemo if indicated
  • Placebo

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.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Disease-free survival (DFS)
Time Frame:at 6 years after first patient in.
Safety Issue:
Description:

Secondary Outcome Measures

Measure:Time to recurrence (TTR)
Time Frame:at 6 years after first patient in.
Safety Issue:
Description:
Measure:Overall survival (OS)
Time Frame:at 6 years after first patient in and trial termination (13 years after first patient in)
Safety Issue:
Description:
Measure:Cancer-specific survival (CSS)
Time Frame:at 6 years after first patient in and trial termination (13 years after first patient in).
Safety Issue:
Description:
Measure:Adverse events (AEs)
Time Frame:at 6 years after first patient in.
Safety Issue:
Description:

Details

Phase:Phase 3
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Swiss Group for Clinical Cancer Research

Trial Keywords

  • Aspirin
  • colon cancer
  • stage II
  • stage III
  • PIK3CA
  • double-blind
  • placebo
  • Adjuvant Treatment

Last Updated

April 16, 2020