Overview
Sponsor-declared trial summary
Phase
Therapeutic confirmatory (Phase III)
Status
Authorised, recruiting
Participants planned
103
Countries
1
Sites
25
Rectal cancer
To investigate whether the disease-free survival in patients with rectal cancer who have detectable ctDNA after primary tumour resection, can be improved by administration of adjuvant chemotherapy
Key facts
- Sponsor
- Erasmus Universitair Medisch Centrum Rotterdam (Erasmus MC)
- Participant type
- Patients
- Age range
- 18-64 years, 65+ years
- Gender
- Male and Female
- Therapeutic area
- Diseases [C] - Digestive System Diseases [C06], Diseases [C] - Neoplasms [C04], Analytical, Diagnostic and Therapeutic Techniques and Equipment [E] - Therapeutics [E02]
- Trial duration
- 10 Dec 2025 → ongoing
- Decision date (initial)
- 2024-10-09
- Transition trial
- Yes
- Low-intervention
- No
- Rare-disease indication
- No
- Vulnerable population
- No
External identifiers
- EU CT number
- 2024-517700-12-00
- EudraCT number
- 2022-002580-30
Trial design
CTIS Part I — objectives, methods, condition coding
Main objective
Scope: Diagnosis, Therapy, Efficacy
To investigate whether the disease-free survival in patients with rectal cancer who have
detectable ctDNA after primary tumour resection, can be improved by administration of
adjuvant chemotherapy
Secondary objectives 6
- To investigate whether overall survival of rectal cancer patients with detectable ctDNA after surgery can be improved with adjuvant chemotherapy
- To compare all (eligible) patients in the control group to patients in the experimental group who actually started the adjuvant chemotherapy by a per protocol analysis (for pure treatment effect) for disease-free and overall survival.
- To compare the effect of adjuvant chemotherapy on quality of life.
- To compare the disease-free survival of patients with detectable ctDNA but without receiving adjuvant chemotherapy with patients with undetectable ctDNA.
- To compare the clearance of ctDNA of the patients who received adjuvant chemotherapy in the experimental group with the patients in the control group.
- To investigate the co-occurrence of ctDNA in peripheral blood at the timing of detection of recurrent disease on imaging.
Conditions and MedDRA coding
Rectal cancer
Eligibility criteria
Principal inclusion / exclusion criteria as submitted by sponsor
Inclusion criteria 8
- Age ≥ 18 years
- WHO performance score 0-1
- Informed consent for PLCRC with specific consent for additional blood withdrawals and offering of future experimental research
- Informed consent for the REACT trial
- Histological confirmed rectal cancer; either treated with neoadjuvant (chemo)radiotherapy, and/or clinical T4 and/or N+ in case no neoadjuvant therapy was administered
- Eligible to receive treatment with combination adjuvant chemotherapy (CAPOX/FOLFOX) according to the treating physician.
- Mentally competent and able to read and understand Dutch language.
- Detectable ctDNA in the postoperative blood sample
Exclusion criteria 11
- Another malignancy in previous 5 years, with the exception of treated carcinoma in situ or skin cancer other than melanoma
- Current or recent (within 28 days prior to randomisation) treatment with another investigational drug or participation in another investigational study.
- Incomplete primary tumour resection (R1 or R2 resection)
- Contra-indication for fluoropyrimidines or oxaliplatin
- Neoadjuvant oxaliplatin based systemic treatment, e.g. treated with the RAPIDO regimen consisting of short course radiotherapy followed by 6 cycles of CAPOX or 9 cycles of FOLFOX prior to surgery
- Patients with a clinical complete response, who will not undergo surger
- Pregnant and lactating women
- History of psychiatric disability judged by the investigator to be clinically significant, precluding informed consent or interfering with compliance of the intervention group
- Serious concomitant systemic disorders that would compromise the safety of the patient or his/her ability to complete the study, at the discretion of the investigator
- Serious infections (uncontrolled or requiring treatment)
- Metastatic disease
Endpoints
Primary and secondary outcome measures (English text)
Primary endpoints 1
- disease-free survival in the intention-to-treat population
Secondary endpoints 6
- Disease-free survival
- Overall survival
- Quality of life
- In addition to intention-to-treat analysis to estimate the effect size, also a per-protocol analysis (for pure treatment effect) will be carried out for disease-free survival and overall survival
- The results of the ctDNA analysis of the blood samples taken at the first follow-up of the randomised patients who were ctDNA positive after surgery will be compared between the patients who received adjuvant chemotherapy and those who did not.
- Within the group of patients with de-tectable ctDNA after surgery, the pro-portion of patients with detectable ctDNA in the peripheral blood at the timing of detection of recurrent dis-ease on imaging will be assessed.
Investigational products
Investigational medicinal products (IMPs), comparators, placebo, auxiliary
Test 4
SCP1165178 · ATC
- Active substance
- Fluorouracil
- Substance synonyms
- 5-FLOUROURACIL, 5-FLUORO-1H-PYRIMIDINE-2,4-DIONE, 5-FLUOROURACIL, 5-FU
- Route of administration
- INTRAVENOUS
- Max daily dose
- 1200 mg/m2 milligram(s)/square meter
- Max total dose
- 16800 mg/m2 milligram(s)/sq. meter
- Max treatment duration
- 12 Week(s)
- Authorisation status
- Authorised
- ATC code
- L01BC02 — FLUOROURACIL
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Folikabi 10 mg/ml oplossing voor injectie/infusie
PRD11854609 · Product
- Active substance
- Calcium Folinate
- Substance synonyms
- LEUCOVORIN CALCIUM
- Pharmaceutical form
- SOLUTION FOR INJECTION/INFUSION
- Route of administration
- INTRAVENOUS
- Max daily dose
- 500 mg/m2 milligram(s)/sq. meter
- Max total dose
- 3000 mg/m2 milligram(s)/sq. meter
- Max treatment duration
- 12 Week(s)
- Authorisation status
- Authorised
- ATC code
- V03AF03 — CALCIUM FOLINATE
- Marketing authorisation
- RVG 116190
- MA holder
- FRESENIUS KABI DEUTSCHLAND GMBH
- MA country
- Netherlands
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
SCP131876 · ATC
- Active substance
- Capecitabine
- Route of administration
- ORAL
- Max daily dose
- 5600 mg milligram(s)
- Max total dose
- 313600 mg milligram(s)
- Max treatment duration
- 12 Week(s)
- Authorisation status
- Authorised
- ATC code
- L01BC06 — CAPECITABINE
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
SCP128961 · ATC
- Active substance
- Oxaliplatin
- Route of administration
- INTRAVENOUS
- Max daily dose
- 130 mg/m2 milligram(s)/sq. meter
- Max total dose
- 520 mg/m2 milligram(s)/sq. meter
- Max treatment duration
- 12 Week(s)
- Authorisation status
- Authorised
- ATC code
- L01XA03 — OXALIPLATIN
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Sponsors and contacts
Sponsor organisations, regulatory contacts, third parties
Erasmus Universitair Medisch Centrum Rotterdam (Erasmus MC)
- Sponsor organisation
- Erasmus Universitair Medisch Centrum Rotterdam (Erasmus MC)
- Address
- Dr. Molewaterplein 40
- City
- Rotterdam
- Postcode
- 3015 GD
- Country
- Netherlands
Scientific contact point
- Organisation
- Erasmus Universitair Medisch Centrum Rotterdam (Erasmus MC)
- Contact name
- Prof.dr. C. Verhoef
Public contact point
- Organisation
- Erasmus Universitair Medisch Centrum Rotterdam (Erasmus MC)
- Contact name
- Prof.dr. C. Verhoef
Locations
1 EU/EEA country · 25 investigational sites
By country
| Country | MS status | Planned subjects | Sites |
|---|---|---|---|
| Netherlands | Authorised, recruiting | 103 | 25 |
| Rest of world | — | 0 | — |
Investigational sites
Ikazia Ziekenhuis
Department of Surgical Oncology, Montessoriweg 1, 3083 AN, Rotterdam
Frisius MC
Department of Medical Oncology, Henri Dunantweg 2, 8934 AD, Leeuwarden
Catharina Ziekenhuis Stichting
Department of Medical Oncology, Michelangelolaan 2, 5623 EJ, Eindhoven
Amsterdam UMC Stichting
Department of Medical Oncology, De Boelelaan 1117, 1081 HV, Amsterdam
Admiraal De Ruyter Ziekenhuis B.V.
Department of Medical Oncology, 'S-Gravenpolderseweg 114, 4462 RA, Goes
Jeroen Bosch Ziekenhuis Stichting
Department of Medical Oncology, Henri Dunantstraat 1, 5223 GZ, 'S-Hertogenbosch
Maasstad Ziekenhuis Stichting
Department of Medical Oncology, Maasstadweg 21, 3079 DZ, Rotterdam
Bravis Ziekenhuis
Department of Medical Oncology, Boerhaavelaan 25, 4708 AE, Roosendaal
Erasmus MC
Surgery, Erasmus MC, Netherlands
Radboud universitair medisch centrum Stichting
Department of Surgery, Geert Grooteplein Zuid 10, 6525 GA, Nijmegen
Stichting Martini Ziekenhuis
Department of Medical Oncology, Van Swietenplein 1, 9728 NT, Groningen
Sint Franciscus Vlietland Groep Stichting
Department of Surgical Oncology, Kleiweg 500, 3045 PM, Rotterdam
Albert Schweitzer Ziekenhuis
Department of Surgical Oncology, Albert Schweitzerplaats 25, 3318 AT, Dordrecht
Reinier de Graaf Groep
Department of Medical Oncology, Reinier De Graafweg 5, 2625 AD, Delft
Meander Medisch Centrum
Department of Medical Oncology, Maatweg 3, 3813 TZ, Amersfoort
Haaglanden Medisch Centrum Stichting
Department of Surgery, Lijnbaan 32, 2512 VA, 'S-Gravenhage
Stichting Elisabeth-Tweesteden Ziekenhuis
Department of Medical Oncology, Hilvarenbeekseweg 60, 5022 GC, Tilburg
ZorgSaam Ziekenhuis
Department of Medical Oncology, Wielingenlaan 2, 4535 PA, Terneuzen
Amphia Hospital
Department of Surgery, Molengracht 21, 4818 CK, Breda
Dijklander Ziekenhuis
Department of Medical Oncology, Maelsonstraat 3, 1624 NP, Hoorn Nh
Canisius Wilhelmina Ziekenhuis
Department of Medical Oncology, Weg Door Jonkerbos 100, 6532 SZ, Nijmegen
Antonius Ziekenhuis Sneek
Department of Surgery, Bolswarderbaan 1, 8601 ZK, Sneek
Ziekenhuisgroep Twente Stichting
Department of Medical Oncology, Zilvermeeuw 1, 7609 PP, Almelo
Bernhoven B.V.
Department of Medical Oncology, Nistelrodeseweg 10, 5406 PT, Uden
Leids Universitair Medisch Centrum (LUMC)
Department of Surgery, Albinusdreef 2, 2333 ZA, Leiden
Country notifications
Trial-start, recruitment-start, end and early-termination notifications submitted per Member State
| Country | Trial start | Trial end | Recruitment start | Recruitment end | Early termination |
|---|---|---|---|---|---|
| Netherlands | 2025-12-10 |
Results and documents
Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial
Documents 15 files
Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.
| Type | Title | Version |
|---|---|---|
| Protocol (for publication) | D1_ Protocol 2024-517700-12-00 CLEAN | 5 |
| Protocol (for publication) | D1_Protocol 2024-517700-12-00 TC | 5 |
| Protocol (for publication) | D4_NL-NL_Patient facing document EORTC C30 | 12 |
| Protocol (for publication) | D4_NL-NL_Patient facing document EORTC CR29 | 12 |
| Protocol (for publication) | D4_NL-NL_Patient facing document EQ-5D-5L | 12 |
| Recruitment arrangements (for publication) | K1_ Recruitment arragements | 1 |
| Recruitment arrangements (for publication) | K2_NL-NL_Other subject information material_ addendum PLCRC-REACT | 2 |
| Recruitment arrangements (for publication) | K2_NL-NL_Recruitment material_zakkaartje REACT | 1 |
| Subject information and informed consent form (for publication) | L1_NL-NL_SIS and ICF adults | 6.1 |
| Subject information and informed consent form (for publication) | L1_NL-NL_SIS and ICF adults TC | 5 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_ SmPC 5-Fluorouracil | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_ SmPC Capecitabine | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_ SmPC Oxaliplatin | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC Folinic acid | 1 |
| Synopsis of the protocol (for publication) | D1_NL-NL_Protocol synopsis 2024-517700-12-00 | 2 |
Application history
4 submissions — initial application plus substantial / non-substantial modifications
| # | Type | Code | Submitted | Reference MS | Conclusion | Decision date |
|---|---|---|---|---|---|---|
| 1 | INITIAL | IN | 2024-09-26 | Netherlands | Acceptable with conditions 2024-10-09
|
2024-10-09 |
| 2 | SUBSTANTIAL MODIFICATION | SM-1 | 2025-07-10 | Netherlands | Acceptable 2025-08-28
|
2025-08-28 |
| 3 | SUBSTANTIAL MODIFICATION | SM-2 | 2025-12-30 | Netherlands | Acceptable 2026-01-20
|
2026-01-20 |
| 4 | SUBSTANTIAL MODIFICATION | SM-3 | 2026-04-28 | Netherlands | Acceptable | 2026-05-28 |