Colon cancer stage II MedDRA version: 21.0 Level: PT Classification code 10009954 Term: Colon cancer stage II System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA version: 21.0 Level: PT Classification code 10038049 Term: Rectal cancer stage II System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Pharmaceutical Form: Tablet
INN or Proposed INN: CAPECITABINE
Other descriptive name: CAPECITABINE
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 500-
Sponsors
Technische Universität Dresden
Eligibility
Sex/Gender
All
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 recommenda- tions for colon cancer. Patients, in whom the tumour stage is not yet know, can be en- rolled 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) Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 2500 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 2312
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 |
|---|---|
| Main Objective: To compare the disease free survival (DFS) with vs. without adjuvant chemotherapy in patients who are positive for ctDNA (ctDNApos) after the resection of the primary tumour .;Secondary Objective: a) to compare the overall survival in colon cancer patients stage II in ctDNA positive patients with and without chemotherapy b) to determine the disease free survival in ctDNA negative patients c) to determine the overall survival of ctDNA negative patients d) to compare the disease free and overall survival in patients without adjuvant therapy according to their ctDNA status e) to compare the site of metastases according to the way of metastases (heamato- vs lymphogenic vs. local/peritoneal) and ctDNA status f) to determine the chemotherapy safety.;Primary end point(s): 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. ;Timepoint(s) of evaluation of this end point: Interims analysis 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 |
|---|---|
| Secondary end point(s): 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).;Timepoint(s) of evaluation of this end point: At the time of the final analysis | — |
Countries
Germany, Switzerland
Contacts
Public Contactcoordinating investigator
Medizinische Fakultät Carl Gustav Carus der TU Dresden, Medizinische Klinik und Poliklinik I
Outcome results
None listed