Clinical Trials /

Adjuvant Low Dose Aspirin in Colorectal Cancer

NCT02647099

Description:

ALASCCA is a randomized, parallel group, double blind, multicenter, placebo-controlled, biomarker-based study of adjuvant treatment with low dose aspirin in patients with colorectal cancer. Hypothesis is that patients diagnosed with colorectal cancer and somatic mutations in PI3K pathway can significantly improve survival if treated with low dose aspirin.

Related Conditions:
  • Colorectal Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 3

Trial Eligibility

Document

Title

  • Brief Title: Adjuvant Low Dose Aspirin in Colorectal Cancer
  • Official Title: A Randomized Double-blind Placebo-controlled Study With ASA Treatment in Colorectal Cancer Patients With Mutations in the PI3K Signaling Pathway

Clinical Trial IDs

  • ORG STUDY ID: 921-2014-7074
  • NCT ID: NCT02647099

Conditions

  • Colorectal Cancer

Interventions

DrugSynonymsArms
Acetylsalicylic acidASA, aspirinAspirin
PlaceboPlacebo

Purpose

ALASCCA is a randomized, parallel group, double blind, multicenter, placebo-controlled, biomarker-based study of adjuvant treatment with low dose aspirin in patients with colorectal cancer. Hypothesis is that patients diagnosed with colorectal cancer and somatic mutations in PI3K pathway can significantly improve survival if treated with low dose aspirin.

Detailed Description

      ALASCCA is a randomized, parallel group, double blind, multicenter, placebo-controlled,
      biomarker-based study of adjuvant treatment with low dose aspirin in colorectal cancer.

      Patients (adult male and female) with colorectal cancer clinical stage I-III with localized
      disease are considered for the study. Patients will be screened for inclusion at the time of
      surgery of the tumor (at time of routine patient visit before elective surgery or
      postoperatively within 12 weeks in case of emergency procedure or if screening was missed
      preoperatively). After inclusion and when surgery is performed, patients with PIK3 mutations
      and stage II and III tumors will be randomized to receive 160 mg aspirin or placebo orally.
      Last date for randomization and start of treatment is 12 weeks postoperatively. The treatment
      can be administered alone or in combination with adjuvant chemotherapy. The choice of any
      adjuvant chemotherapy is made by the Investigator and should follow the guidelines in the
      National Care Program. The treatment will be administered for 3 years. There will be a
      follow-up period for two years. Outside the trial, the patient will be treated according to
      standard care at the site.

      A phone contact will be made 3 months after the randomization visit and thereafter every 6th
      month. The patients will also visit the site 6 months after randomization and thereafter
      every 6th month i.e. the patients will be in contact with the site every 3rd month. There
      will also be a visit/phone contact at the end of the follow-up period.

      A total of 3900 patients will be screened in order to include 408 patients with PIK3CA (Exon
      9 and 20) mutated tumors in each treatment arm (Group A). With an estimated 20 % drop-out
      rate, 204 patients will be randomized in each arm. This also includes approximately 15 % of
      the patients that will be excluded due to tumor stage 1.

      An additional 408 patients with mutations in other PI3K pathway genes PIK3CA (other than exon
      9 and 20), PIK3R1 or PTEN will also be randomized in each arm and will be treated as a
      separate group in the analyses (Group B). With an estimated 20 % drop-out rate, 204 patients
      will be randomized in each arm.

      The randomization process is expected to take 24 months. Patients already treated with ASA at
      inclusion will be included in an observation group.

      An interim analysis will be made on safety i.e incidence and type of serious bleeding
      complication grade > 1 after 12 months. An independent safety data monitoring committee will
      be responsible for evaluating and follow-up of the safety.
    

Trial Arms

NameTypeDescriptionInterventions
AspirinActive ComparatorOne tablet acetylsalicylic acid (ASA) 160 mg, orally once daily for three years
  • Acetylsalicylic acid
PlaceboPlacebo ComparatorOne tablet placebo orally once daily for three years
  • Placebo

Eligibility Criteria

        Inclusion Criteria:

          -  Tumor with somatic alterations in PIK3CA, PIK3R1 or PTEN

          -  Colon or rectal cancer tumor stage II-III

          -  Radical surgery according to surgeon and pathologist

          -  Karnofsky performance status ≥60%

          -  Platelets ≥ 100 x 109 / L

          -  Clean Colonoscopy or Computed Tomography (CT) colon within 3 months preoperatively or
             postoperatively but before randomization

          -  Patient able to swallow tablets

          -  Patient able to understand and sign written informed consent

        Exclusion Criteria:

        Hereditary colorectal cancer linked to familial colonic polyposis or Lynch syndrome

          -  Inflammatory bowel disease (Crohn's disease or ulcerative colitis)

          -  Distant metastases

          -  Other cancers (excluding colorectal cancer or other skin cancer than melanoma) within
             3 years from screening

          -  Known bleeding diathesis (such as hemophilia)

          -  Concomitant antiplatelet therapy (eg clopidrogrel or ticlopidine) or anticoagulant
             therapy (warfarin or low molecular weight heparin). Post-operative treatment with low
             molecular weight heparin must be withdrawn before administration of study treatment

          -  Active gastritis or peptic ulcer, or significant surgical post-op bleeding, within the
             previous three months assessed at screening and randomization

          -  Ongoing regular use of corticosteroids, Nonsteroidal Anti-Inflammatory Drug (NSAID)

          -  Uncontrolled hypertension according to Investigator's judgment

          -  Clinically significant liver impairment according to Investigators judgment

          -  Existing renal failure according to Investigator's judgment. Renal failure with
             decreased creatinine clearance <60 should lead to consultation with a nephrologist.

          -  Significant medical illness that would interfere with study participation

          -  Pregnancy or breastfeeding females

          -  Known allergy to NSAIDs or ASA

          -  Current participation in another clinical trial that will be in conflict with the
             present study

          -  Patients who are unlikely to comply with the protocol (e.g. uncooperative attitude,
             inability to return for subsequent visits) and/or otherwise considered by the
             Investigator to be unlikely to complete the study
      
Maximum Eligible Age:80 Years
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Time To Recurrence (TTR)
Time Frame:3 years
Safety Issue:
Description:local recurrence, distant metastases or death from same cancer

Secondary Outcome Measures

Measure:Disease free survival (DFS)
Time Frame:3 years
Safety Issue:
Description:
Measure:Overall survival (OS)
Time Frame:3 years
Safety Issue:
Description:
Measure:Frequency and severity of adverse events (AE)
Time Frame:1 year and 3 years
Safety Issue:
Description:

Details

Phase:Phase 3
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Anna Martling

Trial Keywords

  • Aspirin
  • PI3K signaling pathway

Last Updated

March 6, 2018