Overview
Sponsor-declared trial summary
Phase
Therapeutic exploratory (Phase II)
Status
Authorised, recruitment pending
Participants planned
40
Countries
1
Sites
4
Patients with colorectal peritoneal metastases with a PCI-score of 1-20
Is treatment, of patients with peritoneal metastases from colorectal origin, of intravenous mFOLFOX4-bevacizumab and intraperitoneal irinotecan (75mg), followed by two cycles of intravenous mFOLFOX4 and intraperitoneal irinotecan) feasible prior to receiving a CRS-HIPEC procedure?
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] - Neoplasms [C04]
- Decision date (initial)
- 2024-10-10
- Transition trial
- No
- Low-intervention
- No
- Rare-disease indication
- No
- Vulnerable population
- No
External identifiers
- EU CT number
- 2024-512318-16-00
- WHO UTN
- U1111-1306-9344
Trial design
CTIS Part I — objectives, methods, condition coding
Main objective
Scope: Others
Is treatment, of patients with peritoneal metastases from colorectal origin, of intravenous mFOLFOX4-bevacizumab and intraperitoneal irinotecan (75mg), followed by two cycles of intravenous mFOLFOX4 and intraperitoneal irinotecan) feasible prior to receiving a CRS-HIPEC procedure?
Secondary objectives 6
- Safety of the administered treatment
- Pathological response after treatment
- Radiological response after treatment
- Superiority of assessment of disease progression by PET-CT vs CT
- Quality of life
- Disease free survival assessment
Conditions and MedDRA coding
Patients with colorectal peritoneal metastases with a PCI-score of 1-20
Eligibility criteria
Principal inclusion / exclusion criteria as submitted by sponsor
Inclusion criteria 9
- Histologically confirmed CRC (colorectal carcinoma)
- Pathologically or radiologically & clinically confirmed, non-appendiceal, adenocarcinoma with PM (peritoneal metastases)
- Synchronous or metachronous PM
- Macroscopic PM still present at time of inclusion/at diagnostic laparoscopy
- Surgical PCI (peritoneal cancer index) score 1 to, or equal to 20 (macroscopic disease)
- No systemic metastases, at enrolment
- WHO-performance score of 0 to 1 with a life expectancy greater than or equal to three months
- Aged above 18 years old
- Written informed consent
Exclusion criteria 16
- Prior cytoreductive surgery and/or HIPEC
- Prior systemic therapy for CRC within the six months before enrolment in this study
- Contra-indications for CRS-HIPEC; contrast administration (allergy)
- Signet cell carcinoma
- Multi drug resistant (MDR) tumors
- Microsatellite instable (MSI) tumour
- Homozygous UGT1A1*28 genotype
- Homozygous dihydropyrimidine dehydrogenase (DPD) deficiency
- Any contra-indication for the (planned) chemotherapy (e.g. active infection, serious concomitant disease, severe allergy, …), as determined by the medical oncologist
- Inadequate organ functions (defined as a haemoglobin <5mmol/l, an absolute neutrophil count <1.5 x 109/l, platelet count <100 x 109/l, serum creatinine >1.5 x ULN, creatinine clearance <30ml/min, bilirubin >2x ULN and liver transaminases >2.5x ULN)
- Major cardiovascular events
- Severe diarrhoea
- Severe stomatitis/ulceration in the mouth or GI-tract
- Unstable or uncompensated respiratory and/or cardiac disease
- Bleeding diathesis or coagulopathy
- Pregnancy or lactation
Endpoints
Primary and secondary outcome measures (English text)
Primary endpoints 1
- The number of patients that is able to undergo all trial treatments (minimally 4 cycles of IP and systemic chemotherapy, followed by CRS-HIPEC)
Secondary endpoints 6
- Measured toxicity in patients during trial treatments (measured by the amount of AE/SAE and SUSAR)
- Pathological response after trial treatment (assessed by the MANDARD scoring system and the Tumor Regression Grading System)
- Radiologic response measured by RECIST and PERCIST (ceCT vs. PET/CT)
- Comparison of PCI-scores of the diagnostic laparoscopy, CRS-HIPEC, PET-CT and CT
- Quality of life assessment via EQ-5D-5L, QLQ-C30, QLQ-CR29, iMTA productivity cost questionnaire (PCQ), and iMTA medical consumption questionnaire (MCQ) at selected points during the trial
- Disease free survival, after CRS-HIPEC, with a follow-up of 6 months
Investigational products
Investigational medicinal products (IMPs), comparators, placebo, auxiliary
Test 5
Fluorouracil Accord 50 mg/ml, oplossing voor injectie of infusie
PRD1972831 · Product
- Active substance
- Fluorouracil
- Pharmaceutical form
- SOLUTION FOR INJECTION/INFUSION
- Route of administration
- INTRAVENOUS ADMINISTRATION
- Max daily dose
- 600 mg/m2 milligram(s)/sq. meter
- Max total dose
- 3600 mg/m2 milligram(s)/sq. meter
- Max treatment duration
- 3 Month(s)
- Authorisation status
- Authorised
- ATC code
- L01BC02 — FLUOROURACIL
- Marketing authorisation
- RVG 100701
- MA holder
- ACCORD HEALTHCARE B.V.
- MA country
- Netherlands
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Calcium Folinate 10 mg/ml Solution for injection or infusion
PRD10040501 · Product
- Active substance
- Folinic Acid
- Pharmaceutical form
- SOLUTION FOR INJECTION/INFUSION
- Route of administration
- INTRAVENOUS ADMINISTRATION
- Max daily dose
- 200 mg/m2 milligram(s)/square meter
- Max total dose
- 1200 mg/m2 milligram(s)/square meter
- Max treatment duration
- 3 Month(s)
- Authorisation status
- Authorised
- ATC code
- V03AF03 — CALCIUM FOLINATE
- Marketing authorisation
- PL 15413/0070
- MA holder
- HIKMA FARMACÊUTICA (PORTUGAL), S.A.
- MA country
- XI
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Avastin 25 mg/ml concentrate for solution for infusion.
PRD2153901 · Product
- Active substance
- Bevacizumab
- Pharmaceutical form
- SOLUTION FOR INFUSION
- Route of administration
- INTRAVENOUS ADMINISTRATION
- Max daily dose
- 10 mg/kg milligram(s)/kilogram
- Max total dose
- 40 mg/Kg milligram(s)/kilogram
- Max treatment duration
- 2 Month(s)
- Authorisation status
- Authorised
- ATC code
- L01FG01 — -
- Marketing authorisation
- EU/1/04/300/001
- MA holder
- ROCHE REGISTRATION GMBH
- MA country
- Iceland
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Oxaliplatin Eugia 5 mg/ml concentraat voor oplossing voor infusie
PRD10195501 · Product
- Active substance
- Oxaliplatin
- Pharmaceutical form
- SOLUTION FOR INFUSION
- Route of administration
- INTRAVENOUS ADMINISTRATION
- Max daily dose
- 85 mg/m2 milligram(s)/sq. meter
- Max total dose
- 510 mg/m2 milligram(s)/sq. meter
- Max treatment duration
- 3 Month(s)
- Authorisation status
- Authorised
- ATC code
- L01XA03 — OXALIPLATIN
- Marketing authorisation
- BE661053
- MA holder
- EUGIA PHARMA (MALTA) LTD
- MA country
- Belgium
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Irinotecanhydrochloridetrihydraat Hikma 20 mg/ml, concentraat voor oplossing voor infusie
PRD735711 · Product
- Active substance
- Irinotecan Hydrochloride Trihydrate
- Pharmaceutical form
- SOLUTION FOR INFUSION
- Route of administration
- INTRAPERITONEAL USE
- Max daily dose
- 180 mg/m2 milligram(s)/sq. meter
- Max total dose
- 1080 mg/m2 milligram(s)/sq. meter
- Max treatment duration
- 3 Month(s)
- Authorisation status
- Authorised
- ATC code
- L01CE02 — -
- Marketing authorisation
- RVG 105025
- MA holder
- HIKMA FARMACÊUTICA (PORTUGAL), S.A.
- MA country
- Netherlands
- 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
- dr. E.V.E. Madsen
Public contact point
- Organisation
- Erasmus Universitair Medisch Centrum Rotterdam (Erasmus MC)
- Contact name
- dr. E.V.E. Madsen
Locations
1 EU/EEA country · 4 investigational sites
By country
| Country | MS status | Planned subjects | Sites |
|---|---|---|---|
| Netherlands | Authorised, recruitment pending | 40 | 4 |
| Rest of world | — | 0 | — |
Investigational sites
Stichting Amsterdam UMC
General Surgery, De Boelelaan 1117, 1081 HV, Amsterdam
Catharina Ziekenhuis Stichting
General Surgery, Michelangelolaan 2, 5623 EJ, Eindhoven
Netherlands Cancer Institute
General Surgery, Plesmanlaan 121, 1066 CX, Amsterdam
Erasmus Universitair Medisch Centrum Rotterdam (Erasmus MC)
General Surgery, Dr. Molewaterplein 40, 3015 GD, Rotterdam
Results and documents
Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial
Documents 9 files
Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.
| Type | Title | Version |
|---|---|---|
| Protocol (for publication) | D1_Protocol 2024-512318-16-00 | 2 |
| Recruitment arrangements (for publication) | K1_Recruitment arrangements NL | 2 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF | 2 |
| Summary of Product Characteristics (SmPC) (for publication) | E1_ SmPC Calcium Folinate | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_ SmPC Irinotecan | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_ SmPC Oxaliplatin | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC Bevacizumab | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC Fluorouracil | 1 |
| Synopsis of the protocol (for publication) | D1_Protocol synopsis NL 2024-512318-16-00 | 1 |
Application history
2 submissions — initial application plus substantial / non-substantial modifications
| # | Type | Code | Submitted | Reference MS | Conclusion | Decision date |
|---|---|---|---|---|---|---|
| 1 | INITIAL | IN | 2024-07-03 | Netherlands | Acceptable 2024-10-07
|
2024-10-10 |
| 2 | NON SUBSTANTIAL MODIFICATION | NSM-1 | 2026-01-02 | Netherlands | Acceptable 2024-10-07
|
2026-01-02 |