Trial document



drksid header

  DRKS00018695

Trial Description

start of 1:1-Block title

Title

Circulating tumour DNA based decision for adjuvant treatment in colon cancer stage II evaluation (CIRCULATE), AIO-KRK-0217

end of 1:1-Block title
start of 1:1-Block acronym

Trial Acronym

CIRCULATE

end of 1:1-Block acronym
start of 1:1-Block url

URL of the Trial

[---]*

end of 1:1-Block url
start of 1:1-Block public summary

Brief Summary in Lay Language

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

end of 1:1-Block public summary
start of 1:1-Block scientific synopsis

Brief Summary in Scientific Language

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

end of 1:1-Block scientific synopsis
start of 1:1-Block forwarded Data

Do you plan to share individual participant data with other researchers?

[---]*

end of 1:1-Block forwarded Data
start of 1:1-Block forwarded Data Content

Description IPD sharing plan:

[---]*

end of 1:1-Block forwarded Data Content
start of 1:1-Block organizational data

Organizational Data

  •   DRKS00018695
  •   2019/12/09
  •   [---]*
  •   yes
  •   Approved
  •   EK-407092019, Ethikkommission der Medizinischen Fakultät der Technischen Universität Dresden
end of 1:1-Block organizational data
start of 1:n-Block secondary IDs

Secondary IDs

  •   2018-003691-12 
end of 1:n-Block secondary IDs
start of 1:N-Block indications

Health Condition or Problem studied

  •   Colon cancer stage II
  •   Rectal cancer stage II, if there was no indication for radiotherapy (i.e. due to the localisation in the upper third of the rectum )
  •   C18 -  Malignant neoplasm of colon
  •   C19 -  Malignant neoplasm of rectosigmoid junction
  •   C20 -  Malignant neoplasm of rectum
end of 1:N-Block indications
start of 1:N-Block interventions

Interventions/Observational Groups

  •   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:
    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)
  •   no Chemotherapie, follw-up
end of 1:N-Block interventions
start of 1:1-Block design

Characteristics

  •   Interventional
  •   [---]*
  •   Randomized controlled trial
  •   Open (masking not used)
  •   [---]*
  •   Control group receives no treatment
  •   Treatment
  •   Parallel
  •   III
  •   N/A
end of 1:1-Block design
start of 1:1-Block primary endpoint

Primary Outcome

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 will be made after 93 events (approx. 38 months after study start), final analysis for the primary endpoint after 154 events (approx. 60 months after study start).

end of 1:1-Block primary endpoint
start of 1:1-Block secondary endpoint

Secondary Outcome

a) Overall survival in ctDNApos patients with adjuvant therapy vs follow-up, measured from randomisation to death from any cause, in all
randomised ctDNA positive patients and be evaluated by a stratified log rank test.
b) Disease free survival in ctDNAneg patients randomised to follow up (rate of patients disease free and alive 3 years after randomisation according to Kaplan-Meier estimation with 95% CI, intention-to-treat
analysis). Any recurrence, metastasis, second colorectal or non-colorectal cancer and death from any cause is regarded as event
c) Overall survival in ctDNAneg patients randomised to "follow up" (rate of patients alive after 5 years after randomisation according to Kaplan-Meier estimation with 95% CI)
d) Disease free and overall survival of ctDNApos vs. ctDNAneg patients randomized to „follow-up" (measured from randomisation to the event
in an intention-to-treat analysis by stratified log rank test). Any recurrence, metastasis, second colorectal or non-colorectal cancer and death from any cause are regarded as event for DFS. Death of any cause will be regarded as event for overall survival.
e) Site of metastases (lymph node vs. peritoneal/local recurrence vs other) in ctDNApos vs. ctDNAneg patients who have a recurrence / metastases
f) Frequency of adverse events from start of chemotherapy until 30 days after chemotherapy (descriptive analysis for patients randomised to
"chemotherapy" who have received at least one dose of chemotherapy).

end of 1:1-Block secondary endpoint
start of 1:n-Block recruitment countries

Countries of Recruitment

  •   Germany
  •   Austria
  •   Switzerland
  •   Belgium
  •   Italy
end of 1:n-Block recruitment countries
start of 1:n-Block recruitment locations

Locations of Recruitment

  • Medical Center 
  • University Medical Center 
  • Doctor's Practice 
end of 1:n-Block recruitment locations
start of 1:1-Block recruitment

Recruitment

  •   Planned
  •   2020/01/12
  •   4812
  •   Multicenter trial
  •   International
end of 1:1-Block recruitment
start of 1:1-Block inclusion criteria

Inclusion Criteria

  •   Both, male and female
  •   18   Years
  •   no maximum age
end of 1:1-Block inclusion criteria
start of 1:1-Block inclusion criteria add

Additional Inclusion 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)

end of 1:1-Block inclusion criteria add
start of 1:1-Block exclusion criteria

Exclusion Criteria

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
a. simultaneous or metachronous colon or rectal cancer with UICC stage ≤ I,
b. curatively treated basal cell carcinoma or squamous cell carcinoma of the skin and in-situ cervical carcinoma
c. tumours with a disease free survival of more than five years
8) Contra indications for chemotherapy, especially:
a. Leukocytes < 3,0 Gpt/l
b. Neutrophil granulocytes < 1,5 Gpt/l
c. Thrombocytes < 100 Gpt/l
d. ALAT or ASAT > 3 x ULN
e. Creatinine clearance (calculated according Cockcroft-Gault) < 30 ml/min
9) Comorbidities relevantly interfering with the prognosis of the patients, i.e.:
a. heart insufficiency NYHA III/IV
b. relevant coronary heart disease,
c. 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”

end of 1:1-Block exclusion criteria
start of 1:n-Block addresses

Addresses

  • start of 1:1-Block address primary-sponsor
    • Technische Universität Dresden
    • 01062  Dresden
    • Germany
    end of 1:1-Block address primary-sponsor
    start of 1:1-Block address contact primary-sponsor
    •   [---]*
    •   [---]*
    •   [---]*
    •   [---]*
    end of 1:1-Block address contact primary-sponsor
  • start of 1:1-Block address scientific-contact
    • Medizinische Fakultät Carl Gustav Carus der TU Dresden, Medizinische Klinik und Poliklinik I
    • Mr.  Prof. Dr. med.  Gunnar  Folprecht 
    • Fetscherstr. 74
    • 01307  Dresden
    • Germany
    end of 1:1-Block address scientific-contact
    start of 1:1-Block address contact scientific-contact
    end of 1:1-Block address contact scientific-contact
  • start of 1:1-Block address public-contact
    • Medizinische Fakultät Carl Gustav Carus der TU Dresden, Medizinische Klinik und Poliklinik I
    • Ms.  Marina  Lindauer 
    • Fetscherstr. 74
    • 01307  Dresden
    • Germany
    end of 1:1-Block address public-contact
    start of 1:1-Block address contact public-contact
    end of 1:1-Block address contact public-contact
end of 1:n-Block addresses
start of 1:n-Block material support

Sources of Monetary or Material Support

  • start of 1:1-Block address materialSupport
    • Bundesinstitut für Arzneimittel und Medizinprodukte
    • Kurt-Georg-Kiesinger-Allee 3
    • 53175  Bonn
    • Germany
    end of 1:1-Block address materialSupport
    start of 1:1-Block address contact materialSupport
    end of 1:1-Block address contact materialSupport
end of 1:n-Block material support
start of 1:1-Block state

Status

  •   Recruiting planned
  •   [---]*
end of 1:1-Block state
start of 1:n-Block publications

Trial Publications, Results and other Documents

end of 1:n-Block publications
* This entry means the parameter is not applicable or has not been set.