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

NCT04089631 | Recruiting Phase 3 DMC

• 4 other identifiers: TUD-CIRC01-0712018-003691-1201KG1817AIO-KRK-0217
• Study Type: interventional
• Target: 4,812
• Locations: 1 country
• Sites: 1

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.

Conditions

Colon Cancer Stage II

Keywords

circulating tumour DNA; ctDNA; adjuvant chemotherapy

Outcome Measures

Primary Outcomes (1)

• Disease free Survival (DFS)

  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).

  for the primary endpoint after 154 events (approx. 60 months after study start)

Secondary Outcomes (6)

• 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

• Disease free and overall survival of ctDNApos vs. ctDNAneg patients randomized to "follow-up"

  3 years and 5 years

• Site of metastases

  5 years

Study Arms (2)

Chemotherapy

EXPERIMENTAL

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)

Drug: Capecitabine

Follow-up

NO INTERVENTION

Patients negative for postoperative ctDNA (ctDNAneg) are randomized (1:4) to follow-up within CIRCULATE or to routine follow up outside the Trial protocol.

Interventions

Capecitabine DRUG

6 months capecitabine, in combination with oxaliplatin 3 to 6 months capecitabine

Also known as: Xeloda

Chemotherapy

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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)

You may not qualify if:

• 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
• 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,

Sponsors & Collaborators

• Technische Universität Dresden: lead

Study Sites (1)

Universitaetsklinikum Carl Gustav Carus, Medizinische Klinik

Dresden, Saxony, 01307, Germany

RECRUITING

MeSH Terms

Conditions

Colonic Neoplasms

Interventions

Capecitabine

Condition Hierarchy (Ancestors)

Colorectal Neoplasms; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases

Intervention Hierarchy (Ancestors)

Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Fluorouracil; Uracil; Pyrimidinones; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Study Officials

• Gunnar Folprecht, Prof.

  University hospital "Carl Gustav Carus" Dresden

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Gunnar Folprecht, Prof.

CONTACT

+49 351 458 4794; Gunnar.Folprecht@uniklinikum-dresden.de

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 9, 2019
• First Posted: September 13, 2019
• Study Start: June 26, 2020
• Primary Completion: June 1, 2023
• Study Completion (Estimated): June 1, 2026
• Last Updated: August 6, 2020

Record last verified: 2020-08

Locations

DE (1)