None listed
Conditions
Brief summary
This study will determine the effect of the use of circulating tumour DNA (ctDNA) to guide adjuvant chemotherapy on recurrence-free survival in stage II colon or rectal cancer patients Who is it for? You may be eligible to join this study if you are aged 18 years or above, and have been diagnosed with Stage II colon or rectal cancer and have had your cancer curatively resected. Study details Participants in this study are randomly allocated (by chance) to one of two groups. Participants in one group will have blood samples taken and analysed for circulating tumour DNA (ctDNA) and be treated according to the ctDNA results. Those with positive ctDNA results will receive standard 5FU-based adjuvant chemotherapy (either single agent or combined with oxaliplatin), while those with negative ctDNA will not receive adjuvant chemotherapy. Participants in the other group will have a blood sample taken, but the ctDNA result will not be disclosed. Patients in this group will be treated according to standard clinical criteria at the discretion of the treating physician. Participants who had positive ctDNA results and are being treated with adjuvant chemotherapy will have monthly blood samples taken during treatment to track ctDNA levels. All participants will be followed up 3 monthly for 2 years, then 6 monthly for 3 years through their hospital for a total of five years for disease recurrence and survival.
Interventions
This is a randomized, multi-centre, biomarker driven adjuvant treatment study involving the collection of blood samples from subjects with curatively resected Stage II colon and rectal cancer. 450 consecutive eligible subjects will be enrolled at participating centres after informed consent is obtained. Patients will be enrolled within 28 days post surgery. Subjects will be randomized 2:1 to be treated according to the ctDNA results (Arm A, n=300), or per standard clinical criteria at the discre
This is a randomized, multi-centre, biomarker driven adjuvant treatment study involving the collection of blood samples from subjects with curatively resected Stage II colon and rectal cancer. 450 consecutive eligible subjects will be enrolled at participating centres after informed consent is obtained. Patients will be enrolled within 28 days post surgery. Subjects will be randomized 2:1 to be treated according to the ctDNA results (Arm A, n=300), or per standard clinical criteria at the discretion of the treating clinician (Arm B, n=150). Resected tumour samples will be made available for mutation analyses. Patients must not have undergone pre-operative chemotherapy or radiotherapy. All patients enrolled will have a blood sample taken at enrollment (week 4) and 3 weeks later (week 7) for initial ctDNA testing. Patients randomized to Arm A and who have positive ctDNA result will receive adjuvant chemotherapy, patients with negative ctDNA result will not receive chemotherapy. Patients randomized to Arm B will be treated at their clinicians discretion. The clinician will initially be blinded to their ctDNA result but results will be provided at or after 6 months post-op following a written request from the site investigator. Patients treated with chemotherapy will receive single agent 5FU-based regimen (including capecitabine) or fluoropyrimidine plus oxaliplatin . Acceptable fluoropyrimidine based chemotherapy regimens include 3-6 months weeks of: 1. 2 weekly De Gramont (modified) a. Leucovorin 50mg IV b. Fluorouracil 400mg/m2 IV c. Fluorouracil 2400mg/m2 CIV pump over 46 hours 2. Weekly modified QUASAR a. Leucovorin 50mg IV b. Fluorouracil 375-450mg/m2 IV (dose as per institutional standard of care) 3. Weekly modified Roswell Park (weekly for 6 weeks followed by 2 week break) a. Leucovorin 50mg IV b. Fluorouracil 500mg/m2 IV 4. Capecitabine PO days 1 to 14, Q21 days (dose as per institutional standard of care) Acceptable Oxaliplatin-based chemotherapy regimens include 3-6 months of: 1. 2 weekly FOLFOX6 (modified) a. Oxaliplatin 85mg/m2 IV b. Leucovorin 50mg IV c. Fluorouracil 400mg/m2 IV d. Fluorouracil 2400mg/m2 CIV pump over 46 hours 2. 3 weekly XELOX/CAPOX a. Oxaliplatin 130mg/m2 b. Capecitabine 1000mg/m2 twice a day PO days 1 to 14, Q21 days
Sponsors
Walter and Eliza Hall Institute
Study design
Allocation
Randomised controlled trial
Intervention model
Parallel
Primary purpose
Treatment
Masking
Open (masking not used)
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Subjects with curatively resected stage II (T3-4, N0M0) colon or rectal cancer. 2. Patients with rectal cancer will be eligible unless they have had pre-operative combined chemotherapy or radiotherapy, or are scheduled for post-operative combined chemotherapy and radiotherapy. All rectal cancer patients included in the trial must have had TME type surgery with negative (R0) resection margins. 3. A representative paraffin embedded tumour sample is avaiable for molecular testing. 4. Fit for adjuvant chemotherapy. 5. ECOG performance status 0-2. 6. Patients that are accessible for follow up. 7. CT C/A/P within 8 weeks demonstrating no metastatic disease.
Exclusion criteria
1. History of another primary cancer within the last 3 years, with the exception of non-melanomatous skin cancer and carcinoma in situ of the cervix. 2. Patients with multiple primary colorectal cancers 3. Patients treated with neoadjuvant chemo-radiation. 4. Medical or psychiatric condition or occupational responsibilities that may preclude compliance with the protocol.
Outcome results
None listed