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

  • STATUS
    Recruiting
  • End date
    Jun 24, 2026
  • participants needed
    4812
  • sponsor
    Technische Universität Dresden
Updated on 24 January 2021

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.

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.

Details
Condition Colon Cancer Stage II
Treatment Capecitabine
Clinical Study IdentifierNCT04089631
SponsorTechnische Universität Dresden
Last Modified on24 January 2021

Eligibility

Yes No Not Sure

Inclusion Criteria

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

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
Clear my responses

How to participate?

Step 1 Connect with a study center
What happens next?
  • You can expect the study team to contact you via email or phone in the next few days.
  • Sign up as volunteer to help accelerate the development of new treatments and to get notified about similar trials.

You are contacting

Investigator Avatar

Primary Contact

site

0/250

Additional screening procedures may be conducted by the study team before you can be confirmed eligible to participate.

Learn more

If you are confirmed eligible after full screening, you will be required to understand and sign the informed consent if you decide to enroll in the study. Once enrolled you may be asked to make scheduled visits over a period of time.

Learn more

Complete your scheduled study participation activities and then you are done. You may receive summary of study results if provided by the sponsor.

Learn more

Similar trials to consider

Loading...

Not finding what you're looking for?

Every year hundreds of thousands of volunteers step forward to participate in research. Sign up as a volunteer and receive email notifications when clinical trials are posted in the medical category of interest to you.

Sign up as volunteer

user name

Added by • 

 • 

Private

Reply by • Private
Loading...

Lorem ipsum dolor sit amet consectetur, adipisicing elit. Ipsa vel nobis alias. Quae eveniet velit voluptate quo doloribus maxime et dicta in sequi, corporis quod. Ea, dolor eius? Dolore, vel!

  The passcode will expire in None.
Loading...

No annotations made yet

Add a private note
  • abc Select a piece of text from the left.
  • Add notes visible only to you.
  • Send it to people through a passcode protected link.
Add a private note