Adjuvant Low Dose Aspirin in Colorectal Cancer

Colorectal Cancer Clinical Trial

— ALASCCA  

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 Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT02647099
• Other study ID #: 921-2014-7074
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: April 7, 2016
• Est. completion date: August 2026

Study information

• Verified date: March 2024
• Source: Karolinska Institutet
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Description:

Patients with colorectal cancer clinical stage I-III will be screened for inclusion at the time of tumor surgery (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. The primary objective is to determine whether adjuvant treatment with 160mg ASA once daily for 3 years can improve time to recurrence in participants with colorectal cancer with somatic alternations in the PI3K singling pathway. UPDATE: New dimensional analysis and power calculation, 19th October 2020: A total of 3900 patients will be screened in order to include 300 patients with PIK3CA (Exon 9 and 20) mutated tumors in each treatment arm (Group A). With an estimated 10 % drop-out rate, 150 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 300 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 10 % drop-out rate, 150 patients will be randomized in each arm. 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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 600
• Est. completion date: August 2026
• Est. primary completion date: August 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

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

Related Conditions & MeSH terms

• Colorectal Cancer
• Colorectal Neoplasms

Intervention

Drug:
• Acetylsalicylic acid

• Placebo

Locations

Country	Name	City	State
Denmark	Aarhus University Hospital	Aarhus
Denmark	Randers Regional Hospital	Randers
Denmark	Viborg Region Hospital	Viborg
Finland	Jorvi Hospital	Espoo
Finland	Meilahti Tower Hospital	Helsinki
Norway	Akershus University Hospital	Oslo
Norway	Stavanger University Hospital	Stavanger
Norway	University Hospital of North Norway	Tromsø
Norway	St Olavs Hospital	Trondheim
Sweden	Falu Hospital	Falun
Sweden	Eastern Hospital	Göteborg
Sweden	Ryhov Hospital	Jönköping
Sweden	Blekinge Hospital (Karlskrona-Karlshamn)	Karlskrona
Sweden	Karlstad Central Hospital	Karlstad
Sweden	Linköping University Hospital	Linköping
Sweden	Sunderby Hospital	Luleå
Sweden	Skåne University Hospital	Malmö
Sweden	Mora Hospital	Mora
Sweden	Vrinnevi Hospital	Norrköping
Sweden	Örebro University Hospital	Örebro
Sweden	Skaraborg Hospital	Skövde
Sweden	Capio S:t Göran Hospital	Stockholm
Sweden	Danderyd Hospital	Stockholm
Sweden	Ersta Hospital	Stockholm
Sweden	Karolinska University Hospital	Stockholm
Sweden	South Hospital	Stockholm
Sweden	Sundsvall Regional Hospital (Sundsvall-Härnösand)	Sundsvall
Sweden	Northern Älvsborg County Hospital	Trollhättan
Sweden	University Hospital of Umeå	Umeå
Sweden	Uppsala University Hospital	Uppsala
Sweden	Västerås Central Hospital	Västerås
Sweden	Ystad Hospital	Ystad

Sponsors (3)

Lead Sponsor	Collaborator
Anna Martling	Skane University Hospital, Uppsala University Hospital

Countries where clinical trial is conducted

Denmark,  Finland,  Norway,  Sweden, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Time To Recurrence (TTR)	Defined as local recurrence, distant metastases or death from same cancer.	3 years
Secondary	Disease free survival (DFS)		3 years
Secondary	Overall survival (OS)		3 years
Secondary	Frequency and severity of adverse events (AE)		1 year and 3 years