Circulating Tumour DNA Based Decision for Adjuvant Treatment in Colon Cancer Stage II Evaluation

Summary

The CIRCULATE study evaluates the adjuvant therapy in patients with colon cancer UICC stage II. The primary aim of the study is to compare the disease free survival in patients who are positive for postoperative circulating tumour DNA with vs. without capecitabine.

Eligibility

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 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

   1. simultaneous or metachronous colon or rectal cancer with UICC stage ≤ I,
   2. curatively treated basal cell carcinoma or squamous cell carcinoma of the skin and in-situ cervical carcinoma
   3. tumours with a disease free survival of more than five years
8. Contra indications for chemotherapy, especially:

   1. Leukocytes \< 3,0 Gpt/l
   2. Neutrophil granulocytes \< 1,5 Gpt/l
   3. Thrombocytes \< 100 Gpt/l
   4. alanine aminotransferase (ALAT) or (aspartate aminotransferase) ASAT \> 3x ULN
   5. Creatinine clearance (calculated according Cockcroft-Gault) \< 30 ml/min
9. Comorbidities relevantly interfering with the prognosis of the patients, i.e.:

   1. heart insufficiency NYHA III/IV
   2. relevant coronary heart disease,
   3. 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 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"

Conditions2

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