Circulate

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Technische Universitat Dresden

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

4 Dec 2019 → 31 Jan 2026

Decision date (initial)

2024-04-22

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

German Aerospace Centre · German Federal Ministry for Education and Research

External identifiers

EU CT number

2023-506715-18-00

EudraCT number

2018-003691-12

ClinicalTrials.gov

NCT04089631

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy

The study evaluates the adjuvant therapy in patients with colon cancer UICC stage II. To compare the disease free survival (DFS) in patients who are positive for ctDNA (ctDNApos) after the resection of the primary tumour with vs. without adjuvant therapy.

Secondary objectives 10

1. to compare the overall survival in colon cancer patients stage II in ctDNA positive patients with and without chemotherapy
2. to determine the disease free survival in ctDNA negative patients
3. to determine the overall survival of ctDNA negative patients
4. to compare the disease free and overall survival in pa- tients without adjuvant therapy according to their ctDNA status
5. to compare the site of metastases according to the way of metastases (heamato- vs lymphogenic vs. local/peritoneal) and ctDNA status
6. to determine the chemotherapy safety
7. to determine the rate and time of conversion to ctDNA negativity during chemotherapy
8. ctDNA level before recurrence
9. to determine the DFS according to the ctDNA level
10. to explore further molecular tissue and plasma marker that are prognostic for recurrence or predictive for the chemotherapy effect such as CDX2 in the tissue, immune infiltrating cells, immune related polymorphisms

Conditions and MedDRA coding

colon cancer stage II, rectal cancer stage II

Study design 2 periods

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 4

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 and the randomised phase
3. Known microsatellite or mismatch repair status
4. Confirmation, that the ctDNA result is available

Exclusion criteria 23

1. Patients with known microsatellite instability (MSI-H) or mis- match repair deficiency (dMMR)
2. Known clinical high risk situation if it is regarded as certain in- dication for an adjuvant chemotherapy
3. Patients, who have an obvious contra-indication for adjuvant chemotherapy (i.e. due to the performance status, comorbid- ity, 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 un- feasible due to logistic reasons (travel distance, compliance)
6. Age < 18 years
7. Pregnant or breast feeding patients
8. R1- or R2- status, or unknown R- status (Rx)
9. Number of investigated lymph nodes < 10 5) WHO performance status ≥ 2
10. Colon or rectal cancer with UICC stage III or IV
11. Second cancer, except: simultaneous or metachronous colon or rectal cancer with UICC stage ≤ I, OR curatively treated basal cell carcinoma or squamous cell carcinoma of the skin and in-situ cervical carcinoma OR tumours with a disease free survival of more than five years
12. 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
13. 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
14. Organ, stem cell or bone marrow transplantation
15. Known hypersensitivity to capecitabine. In case of known hypersensitivity to oxaliplatin, the patients can participate, but not receive oxaliplatin.
16. Medication with brivudine, sorivudine or analogues in the last four weeks before planned treatment start.
17. Known biallelic or homozygous dihydropyrimidine dehydro- genase (DPD)-deficiency
18. Acute infections
19. Known HIV- infections, known active hepatitis B or C- infection
20. Participation at another interventional study for medical treat- ment during the last four weeks before randomisation
21. Neoadjuvant therapy before resection
22. Patients, in whom the randomisation or chemotherapy is un- feasible due to logistic reasons (travel distance, compliance)
23. 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”

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Disease free survival of ctDNA positive patients randomised to “chemo- therapy” vs. “follow-up”, measured from randomisation to any recur- rence, 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.

Secondary endpoints 10

1. 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 evalu- ated by a stratified log rank test.
2. 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
3. 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).
4. Disease free and overall survival of ctDNApos vs. ctDNAneg pa- tients 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.
5. Site of metastases (lymph node vs. peritoneal/local recurrence vs other) in ctDNApos vs. ctDNAneg patients who have a recur- rence / metastases.
6. 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).
7. Rate of patients in which ctDNA becomes non-measurable during or after chemotherapy (measured in ctDNApos patients receiving chemotherapy) and time to the first negative sample
8. ctDNA level before recurrence
9. DFS according to ctDNA level at time of enrolment
10. Correlation of further molecular tissue and plasma marker to the risk of recurrence or metastases or the effect of chemo- therapy (exploratory analysis)

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Technische Universitat Dresden

Sponsor organisation

Technische Universitat Dresden

Address

Mommsenstrasse 11, Raecknitz/zschertnitz Raecknitz/zschertnitz

City

Dresden

Postcode

01069

Country

Germany

Locations

2 EU/EEA countries · 142 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 27 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

16 submissions — initial application plus substantial / non-substantial modifications