Colon cancer stage II Rectal cancer stage II, if there was no indication for radiotherapy (i.e. due to the localisation in the upper third of the rectum ) C18 C19 C20
Conditions
Interventions
Group 1: Capecitabine 2 x 1250 mg/m^2, oral (d1-14), repeated at day 22 (- 2 ... + 6 days). Patients with a GFR between 30 and 50 ml/min start with capecitabine dose of 2 x 1000 mg/m^2. Treatment dura
Sponsors
Technische Universität Dresden
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Inclusion criteria
Inclusion criteria: Inclusion criteria for screening phase: 1) Resected colon cancer stage II, OR Resected rectal cancer stage II, if there was no indication for radiotherapy (i.e. due to the localisation in the upper third of the rectum ), so that the treatment follows the recommendations for colon cancer. Patients, in whom the tumour stage is not yet know, can be enrolled into the screening. 2) Signed informed consent for the screening Phase Inclusion criteria for the randomised phase: 1) Resected colon cancer stage II, OR resected rectal cancer stage II, if there was no indication for radiotherapy (i.e. due to the localisation in the upper third of the rectum), so that the treatment follows the recommendations for colon cancer. 2) Known microsatellite or mismatch repair status 3) Confirmation, that the ctDNA result is available 4) Signed second informed consent (for the randomised phase)
Exclusion criteria
Exclusion criteria: Exclusion criteria for Screening: 1) Patients with known microsatellite instability (MSI-H) or mismatch repair deficiency (dMMR) 2) Known clinical high risk situation if it is regarded as certain indication for an adjuvant chemotherapy 3) Patients, who have an obvious contra-indication for adjuvant chemotherapy (i.e. due to the performance status, comorbidity, active second cancer or age). It should be considered that patients with an age of more than 75 years frequently not fulfil criteria for adjuvant chemotherapy. 4) R1- or R2-status (patients with [still] unknown R-status can be screened) 5) Patients, in whom the randomisation or chemotherapy is unfeasible due to logistic reasons (travel distance, compliance) 6) Age 3 x ULN e. Creatinine clearance (calculated according Cockcroft-Gault) < 30 ml/min 9) Comorbidities relevantly interfering with the prognosis of the patients, i.e.: a. heart insufficiency NYHA III/IV b. relevant coronary heart disease, c. Diabetes mellitus with late sequelae 10) Organ, stem cell or bone marrow transplantation 11) Known hypersensitivity to capecitabine In case of known hypersensitivity to oxaliplatin, the patients can participate, but not receive oxaliplatin 12) Medication with brivudine, sorivudine or analogues in the last four weeks before planned treatment start 13) Known biallelic or homozygous dihydropyrimidine dehydrogenase (DPD)-deficiency 14) Acute infections 15) Known HIV- infections, known active hepatitis B or C-infection 16) Participation at another interventional study for medical treatment during the last four weeks before randomisation 17) Neoadjuvant therapy before resection 18) Patients, in whom the randomisation or chemotherapy is unfeasible due to logistic reasons (travel distance, compliance) 19) Age < 18 years 20) Pregnant or breast feeding patients 21) Women of childbearing potential and men with partner with childbearing potential who are not willing to take appropriate precautions to avoid pregnancy with a highly effective method in case they are randomised to “chemotherapy”
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Disease free survival of ctDNA positive patients randomised to "chemotherapy" vs. "follow-up", measured from randomisation to any recurrence, metastasis, second colorectal or non colorectal cancer and death from any cause. The primary endpoint will be tested in all randomised ctDNA positive patients and be evaluated by a stratified log rank test. Interims Analysis will be made after 93 events (approx. 38 months after study start), final analysis for the primary endpoint after 154 events (approx. 60 months after study start). | — |
Secondary
| Measure | Time frame |
|---|---|
| a) Overall survival in ctDNApos patients with adjuvant therapy vs follow-up, measured from randomisation to death from any cause, in all randomised ctDNA positive patients and be evaluated by a stratified log rank test. b) Disease free survival in ctDNAneg patients randomised to follow up (rate of patients disease free and alive 3 years after randomisation according to Kaplan-Meier estimation with 95% CI, intention-to-treat analysis). Any recurrence, metastasis, second colorectal or non-colorectal cancer and death from any cause is regarded as event c) Overall survival in ctDNAneg patients randomised to "follow up" (rate of patients alive after 5 years after randomisation according to Kaplan-Meier estimation with 95% CI) d) Disease free and overall survival of ctDNApos vs. ctDNAneg patients randomized to „follow-up" (measured from randomisation to the event in an intention-to-treat analysis by stratified log rank test). Any recurrence, metastasis, second colorectal or non-colorectal cancer and death from any cause are regarded as event for DFS. Death of any cause will be regarded as event for overall survival. e) Site of metastases (lymph node vs. peritoneal/local recurrence vs other) in ctDNApos vs. ctDNAneg patients who have a recurrence / metastases f) Frequency of adverse events from start of chemotherapy until 30 days after chemotherapy (descriptive analysis for patients randomised to "chemotherapy" who have received at least one dose of chemotherapy). | — |
Countries
Austria, Germany
Contacts
Public ContactLydia Reinhardt
Medizinische Fakultät Carl Gustav Carus der TU Dresden, Medizinische Klinik und Poliklinik I
Outcome results
None listed