Circulating Tumour DNA Based Decision for Adjuvant Treatment in Colon Cancer Stage II Evaluation (CIRCULATE)
Colon Cancer Stage II
About this trial
This is an interventional treatment trial for Colon Cancer Stage II focused on measuring circulating tumour DNA, ctDNA, adjuvant chemotherapy
Eligibility Criteria
Inclusion criteria for screening phase:
- 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.
- Signed informed consent for the screening Phase
Inclusion criteria for the randomised phase:
- 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.
- Known microsatellite or mismatch repair status
- Confirmation, that the ctDNA result is available
- Signed second informed consent (for the randomised phase)
Exclusion criteria for Screening:
- Patients with known microsatellite instability (MSI-H) or mismatch repair deficiency (dMMR)
- Known clinical high risk situation if it is regarded as certain indication for an adjuvant chemotherapy
- 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.
- R1- or R2-status (patients with [still] unknown R-status can be screened)
- Patients, in whom the randomisation or chemotherapy is unfeasible due to logistic reasons (travel distance, compliance)
- Age < 18 years
- Pregnant or breast feeding patients
Exclusion criteria for randomised phase:
- Patients with microsatellite instability (MSI-H) or mismatch repair deficiency (dMMR)
- Known clinical high risk situation if it is regarded as certain indication for an adjuvant chemotherapy
- R1- or R2- status, or unknown R- status (Rx)
- Number of investigated lymph nodes < 10
- WHO performance status ≥ 2
- Colon or rectal cancer with UICC stage III or IV
Second cancer, except
- simultaneous or metachronous colon or rectal cancer with UICC stage ≤ I,
- curatively treated basal cell carcinoma or squamous cell carcinoma of the skin and in-situ cervical carcinoma
- tumours with a disease free survival of more than five years
Contra indications for chemotherapy, especially:
- Leukocytes < 3,0 Gpt/l
- Neutrophil granulocytes < 1,5 Gpt/l
- Thrombocytes < 100 Gpt/l
- alanine aminotransferase (ALAT) or (aspartate aminotransferase) ASAT > 3x ULN
- Creatinine clearance (calculated according Cockcroft-Gault) < 30 ml/min
Comorbidities relevantly interfering with the prognosis of the patients, i.e.:
- heart insufficiency NYHA III/IV
- relevant coronary heart disease,
- Diabetes mellitus with late sequelae
- Organ, stem cell or bone marrow transplantation
- Known hypersensitivity to capecitabine In case of known hypersensitivity to oxaliplatin, the patients can participate, but not receive oxaliplatin
- Medication with brivudine, sorivudine or analogues in the last four weeks before planned treatment start
- Known dihydropyrimidine dehydrogenase (DPD)-deficiency
- Acute infections
- Known HIV- infections, known active hepatitis B or C-infection
- Participation at another interventional study for medical treatment during the last four weeks before randomisation
- Neoadjuvant therapy before resection
- Patients, in whom the randomisation or chemotherapy is unfeasible due to logistic reasons (travel distance, compliance)
- Age < 18 years
- Pregnant or breast feeding patients
- 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"
Sites / Locations
- Universitaetsklinikum Carl Gustav Carus, Medizinische KlinikRecruiting
Arms of the Study
Arm 1
Arm 2
Experimental
No Intervention
Chemotherapy
Follow-up
Capecitabine mono or Capecitabine/Oxaliplatin as investigator choice: Patients who are positive for postoperative ctDNA (ctDNApos) and not microsatellite instable are randomized (2:1) to adjuvant chemotherapy with capecitabine or to follow up. 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 duration: 8 cycles (approx. 6 months) Capecitabine, if combined with Oxaliplatin (investigator choice): If the investigation decides to add oxaliplatin, the following schedule should be used: [Oxaliplatin 130 mg/m^2 i.v. (2 hours on d1)] Capecitabine 2 x 1000 mg/m^2, oral (d1-14), repeated at day 22 (- 2 ... + 6 days) Treatment duration: 4 or 8 cycles (approx. 3 or 6 months)
Patients negative for postoperative ctDNA (ctDNAneg) are randomized (1:4) to follow-up within CIRCULATE or to routine follow up outside the Trial protocol.