Circulating tumour DNA based decision for adjuvant treatment in colon cancer stage II evaluation (CIRCULATE), AIO-KRK-0217

Recruitment & Eligibility

Status: Recruiting

Sex: All

Target Recruitment: 4812

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 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 < 18 years
7) Pregnant or breast feeding patients
Exclusion criteria for randomised phase:
1) Patients with 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) R1- or R2- status, or unknown R- status (Rx)
4) Number of investigated lymph nodes < 10
5) WHO performance status = 2
6) Colon or rectal cancer with UICC stage III or IV
7) Second cancer, except
a. simultaneous or metachronous colon or rectal cancer with UICC stage = I,
b. curatively treated basal cell carcinoma or squamous cell carcinoma of the skin and in-situ cervical carcinoma
c. tumours with a disease free survival of more than five years
8) Contra indications for chemotherapy, especially:
a. Leukocytes < 3,0 Gpt/l
b. Neutrophil granulocytes < 1,5 Gpt/l
c. Thrombocytes < 100 Gpt/l
d. ALAT or ASAT > 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”

Study & Design

Study Type: interventional

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
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. <br><br>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 Outcome Measures

Name	Time	Method

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