Circulating Tumour DNA Based Decision for Adjuvant Treatment in Colon Cancer Stage II Evaluation (CIRCULATE) AIO-KRK-0217
Overview
- Phase
- Phase 3
- Intervention
- Capecitabine
- Conditions
- Colon Cancer Stage II
- Sponsor
- Technische Universität Dresden
- Enrollment
- 4812
- Locations
- 1
- Primary Endpoint
- Disease free Survival (DFS)
- Status
- Recruiting
- Last Updated
- 5 years ago
Overview
Brief 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.
Detailed Description
CIRCULATE is an investigator-initiated, multicentre, prospective, randomised, controlled trial. Screening phase: Patients with colon cancer (or rectal cancer, if a radiation is not indicated i.e. due to the tumour localisation) are postoperatively screened for this trial. For this purpose, they sign an informed consent for screening. The formalin fixed paraffin embedded (FFPE) tumour block is shipped to one of the central pathological laboratories and is analysed for microsatellite instability and by panel analysis for frequent mutations in the colorectal cancer. A plasma sample is sent in parallel to the central laboratory for ctDNA. The screening is preferably performed before the patient is discharged from the surgical department and at the latest 5 weeks after resection to allow sufficient time for the analysis. The patient- specific tumour mutations known from the panel analysis are measure in the patients plasma by ultra deep sequencing. The results of the analysis - positive for circulating tumour DNA (ctDNApos) or negative for circulating tumour DNA (ctDNAneg) - is not communicated to the patient or the investigator. Randomised phase: Four to eight weeks after resection, the patient presents at an investigator that is experienced with chemotherapy (i.e. Medical Oncologist) and consent for the randomised part of the study with a second informed consent form. If this baseline visit confirms that there are not contraindications to chemotherapy and if no other exclusion criteria exist, the patient is randomised: * ctDNApos patients are randomised (2:1) in "chemotherapy" (with capecitabine) or "follow-up", * ctDNAneg patients are randomised (1:4) in "follow-up" or "off study" which means that the follow-up will be organised within the routine clinical practice. The result of the ctDNA will not be communicated to the patients and investigators, so that patients in the arm "follow-up" remain blinded to the ctDNA result. Due to the randomisation ratio, the prognosis of these patients is similar to those in stage II without any ctDNA analysis and differs only slightly from patients not enrolled into a clinical trial. Patients in the arm "chemotherapy" receive adjuvant therapy with 6 months capecitabine. The investigator can decide to add oxaliplatin and to shorten the adjuvant chemotherapy to 3 months if oxaliplatin is added. Patients in the arms "chemotherapy" and "follow-up" are followed with the same methods and time point within the study. Patients in the arm "off study" are recommended to be follow up according to the guidelines for stage II in the routine practice.
Investigators
Eligibility Criteria
Inclusion Criteria
- Not provided
Exclusion Criteria
- Not provided
Arms & Interventions
Chemotherapy
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)
Intervention: Capecitabine
Outcomes
Primary Outcomes
Disease free Survival (DFS)
Time Frame: for the primary endpoint after 154 events (approx. 60 months after study start)
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 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 Outcomes
- Disease free and overall survival of ctDNApos vs. ctDNAneg patients randomized to "follow-up"(3 years and 5 years)
- Overall survival in ctDNApos patients with adjuvant therapy vs follow-up(5 years)
- Disease free survival in ctDNAneg patients randomised to follow up(3 years)
- Overall survival in ctDNAneg patients randomised to "follow up"(5 years)
- Site of metastases(5 years)
- Frequency of adverse events from start of chemotherapy until 30 days after chemotherapy(5 years)