| Objective: |
Primary objective
• To determine whether adjuvant treatment with 160 mg Acetylsalicylic Acid (ASA) once daily for 3 years can improve Time To Recurrence (TTR) in patients with colorectal cancer with somatic alterations in the PIK3CA (exon 9 and 20), compared with placebo.
Secondary objective
• To determine whether adjuvant treatment with 160 mg ASA once daily for 3 years can improve Disease-Free Survival (DFS) in patients with colorectal cancer with somatic alterations in the PIK3CA (exon 9 and 20) compared with placebo.
• To determine whether adjuvant treatment with 160 mg ASA once daily for 3 years can improve DFS in patients with colorectal cancer with somatic alterations in the PIK3CA (other than exon 9 and 20), PIK3R1 or PTEN genes, compared with placebo.
• To determine whether adjuvant treatment with 160 mg ASA once daily for 3 years can improve TTR in patients with colorectal cancer with somatic alterations in the PIK3CA (other than exon 9 and 20), PIK3R1 or PTEN genes compared with placebo.
• To compare overall survival (OS) at 5 years from randomization in patients receiving low-dose ASA compared with placebo.
• To assess overall safety and tolerability.
Primary Endpoint
• TTR at 3 years, in patients with tumors harboring PIK3CA mutations in exon 9 and 20 Secondary Endpoints
• DFS at 3 years, in patients with tumors harboring PIK3CA mutations in exon 9 and 20.
• DFS at 3 years, in patients with tumors harboring PIK3CA mutations other than in exon 9 and 20 and in PIK3R1 and PTEN.
• TTR at 3 years, in patients with tumors harboring PIK3CA mutations other than in exon 9 and 20 and in PIK3R1 and PTEN.
• OS at 5 years, in patients with tumors harboring PIK3CA mutations in exon 9 and 20, other than in exon 9 and 20 and in PIK3R1 and PTEN. Safety Endpoints
• Frequency and severity of adverse events (AE)
• Cerebral and gastric haemorrhage (for interims analysis)
Exploratory objectives
• Description and presentation of data on patients already on administration with ASA
• In a technical pilot study (50 patients), ensure the handling and shipping of the gene samples "
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| Aim: |
To study whether patients diagnosed with colorectal cancer and somatic mutations in PI3K pathway can have significantly improve survival if treated with low dose aspirin |
| Methods: |
Overall trial design ALASCCA is a randomized, parallel group, double blind, multicenter, placebo-controlled, biomarker-based study of adjuvant treatment with ASA in colorectal cancer. The study will compare DFS, time to relapse and OS and will assess safety and tolerability. 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 ASA 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 (www.cancercentrum.se). 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.
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| Reason for International Trial: |
Improve feasibility, acheive a high inclusion rate, promote and encourage European research collaboration
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