Evaluating adjuvant treatment options for stage II colon cancer using circulating tumor DNA

Circulating Tumour DNA Based Decision for Adjuvant Treatment in Colon Cancer Stage II Evaluation (CIRCULATE) AIO-KRK-0217

This study tests if giving extra treatment after surgery helps people with stage II colon cancer who have certain markers in their blood do better than those who don’t.

Quick facts

• Phase: PHASE3
• Study type: Interventional
• Enrollment: 4812 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Technische Universität Dresden (other)
• Drugs / interventions: chemotherapy, radiation
• Locations: 1 site (Dresden, Saxony)
• Trial ID: NCT04089631 on ClinicalTrials.gov

What this trial studies

The CIRCULATE study investigates the effectiveness of adjuvant therapy in patients with stage II colon cancer by comparing disease-free survival rates between those who test positive for circulating tumor DNA (ctDNA) and those who do not. This multicenter, prospective, randomized, controlled trial involves screening patients post-surgery for ctDNA and other tumor characteristics before randomizing them to receive capecitabine or not. The study aims to provide insights into personalized treatment approaches based on ctDNA status.

Who should consider this trial

Good fit: Ideal candidates include patients with resected stage II colon cancer or rectal cancer without indications for radiotherapy.

Not a fit: Patients with known microsatellite instability or mismatch repair deficiency may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could lead to more tailored adjuvant treatment strategies for patients with stage II colon cancer, potentially improving their disease-free survival.

How similar studies have performed: Other studies have shown promise in using ctDNA for treatment decision-making in various cancers, suggesting this approach may be beneficial.

Eligibility 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 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"

Where this trial is running

Dresden, Saxony

• Universitaetsklinikum Carl Gustav Carus, Medizinische Klinik — Dresden, Saxony, Germany (RECRUITING)

Study contacts

• Principal investigator: Gunnar Folprecht, Prof. — University hospital "Carl Gustav Carus" Dresden
• Study coordinator: Gunnar Folprecht, Prof.

Conditions: Colon Cancer Stage II, circulating tumour DNA, ctDNA, adjuvant chemotherapy