Kliniska prövningar Nct sida

Summary
EudraCT Number:2022-002214-17
Sponsor's Protocol Code Number:NL78220.029.21
National Competent Authority:Netherlands - Competent Authority
Clinical Trial Type:EEA CTA
Trial Status:Ongoing
Date on which this record was first entered in the EudraCT database:2023-03-31
Trial results
Index
A. PROTOCOL INFORMATION
B. SPONSOR INFORMATION
C. APPLICANT IDENTIFICATION
D. IMP IDENTIFICATION
D.8 INFORMATION ON PLACEBO
E. GENERAL INFORMATION ON THE TRIAL
F. POPULATION OF TRIAL SUBJECTS
G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
P. END OF TRIAL
A. Protocol Information
A.1Member State ConcernedNetherlands - Competent Authority
A.2EudraCT number2022-002214-17
A.3Full title of the trial
COLLISION RELAPSE trial - Recurrent colorectal liver metastases: repeat local treatment +/- neoadjuvantsystemic therapy - a phase III prospective randomized controlled trial
COLLISION RELAPSE trial - Recidief colorectale levermetastasen: lokale behandeling +/- neoadjuvantesystemische therapie - een fase III prospectieve gerandomiseerde studie
A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
Repeat local treatment +/- neoadjuvant systemic therapy for recurrent colorectal liver metastases.
Lokale behandeling +/- neoadjuvant systemische therapie voor recidieven van leveruitzaaiingen van dikke- en endeldarmkanker.
A.3.2Name or abbreviated title of the trial where available
COLLISION RELAPSE - Repeat local treatment +/- neoadjuvant systemic therapy
COLLISION RELAPSE - Lokale behandeling +/- neoadjuvant systemische therapie
A.4.1Sponsor's protocol code numberNL78220.029.21
A.7Trial is part of a Paediatric Investigation Plan No
A.8EMA Decision number of Paediatric Investigation Plan
B. Sponsor Information
B.Sponsor: 1
B.1.1Name of SponsorAmsterdam University Medical Centers
B.1.3.4CountryNetherlands
B.3.1 and B.3.2Status of the sponsorNon-Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1Name of organisation providing supportAmsterdam University Medical Centers
B.4.2CountryNetherlands
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1Name of organisationAmsterdam University Medical Centers
B.5.2Functional name of contact pointInterventional Radiology dep.
B.5.3 Address:
B.5.3.1Street AddressBoelelaan 1117
B.5.3.2Town/ cityAmsterdam
B.5.3.3Post code1081 HV
B.5.3.4CountryNetherlands
B.5.6E-mailm.dijkstra3@amsterdamumc.nl
D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3IMP RoleTest
D.2 Status of the IMP to be used in the clinical trial
D.2.1IMP to be used in the trial has a marketing authorisation Yes
D.2.1.1.1Trade name CAPOX (capecitabine with oxaliplatin) FOLFOX/FOLFIRI (5-fluorouracil/leucovorin with oxaliplatin or irinotecan) (with or without bevacizumab, per-patient based)
D.2.1.2Country which granted the Marketing AuthorisationEuropean Union
D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
D.2.5.1Orphan drug designation number
D.3 Description of the IMP
D.3.1Product nameCAPOX (capecitabine with oxaliplatin) FOLFOX/FOLFIRI (5-fluorouracil/leucovorin with oxaliplatin or
D.3.4Pharmaceutical form Concentrate for solution for infusion
D.3.4.1Specific paediatric formulation No
D.3.7Routes of administration for this IMPIntravenous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8INN - Proposed INNCapecitabine
D.3.9.3Other descriptive nameCapecitabine
D.3.9.4EV Substance CodeSUB12474MIG
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8INN - Proposed INNOxaliplatin
D.3.9.1CAS number 61825-94-3
D.3.9.4EV Substance CodeSUB09490MIG
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8INN - Proposed INNFluorouracil
D.3.9.3Other descriptive nameFluorouracil
D.3.9.4EV Substance CodeSUB07721MIG
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8INN - Proposed INNLEVOLEUCOVORIN
D.3.9.1CAS number 68538-85-2
D.3.9.3Other descriptive nameLEVOLEUCOVORIN
D.3.9.4EV Substance CodeSUB34736
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8INN - Proposed INNIrinotecan
D.3.9.1CAS number 97682-44-5
D.3.9.4EV Substance CodeSUB08295MIG
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8INN - Proposed INNBevacizumab
D.3.9.1CAS number 216974-75-3
D.3.9.4EV Substance CodeSUB16402MIG
D.3.11 The IMP contains an:
D.3.11.1Active substance of chemical origin Yes
D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) No
The IMP is a:
D.3.11.3Advanced Therapy IMP (ATIMP) No
D.3.11.3.1Somatic cell therapy medicinal product No
D.3.11.3.2Gene therapy medical product No
D.3.11.3.3Tissue Engineered Product No
D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
D.3.11.5Radiopharmaceutical medicinal product No
D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
D.3.11.7Plasma derived medicinal product No
D.3.11.8Extractive medicinal product No
D.3.11.9Recombinant medicinal product No
D.3.11.10Medicinal product containing genetically modified organisms No
D.3.11.11Herbal medicinal product No
D.3.11.12Homeopathic medicinal product No
D.3.11.13Another type of medicinal product No
D.8 Information on Placebo
E. General Information on the Trial
E.1 Medical condition or disease under investigation
E.1.1Medical condition(s) being investigated
Recurrent colorectal liver metastases
Recidief colorectale levermetastasen
E.1.1.1Medical condition in easily understood language
Recurrent liver metastases from colorectal cancer
Recidief lever uitzaaiingen van dikke- en endeldarmkanker
E.1.1.2Therapeutic area Diseases [C] - Cancer [C04]
MedDRA Classification
E.1.2 Medical condition or disease under investigation
E.1.2Version 21.0
E.1.2Level PT
E.1.2Classification code 10052358
E.1.2Term Colorectal cancer metastatic
E.1.2System Organ Class 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
E.1.2 Medical condition or disease under investigation
E.1.2Version 20.0
E.1.2Level LLT
E.1.2Classification code 10024700
E.1.2Term Liver metastases
E.1.2System Organ Class 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
E.1.3Condition being studied is a rare disease No
E.2 Objective of the trial
E.2.1Main objective of the trial
The primary objective is to demonstrate superiority of neoadjuvant systemic therapy followed by repeat local treatment as compared to upfront repeat local treatment in patients with at least one locally treatable recurrent CRLM in the absence of extrahepatic disease. Primary objective is to compare overall survival (OS) in both study arms, counting from the date of randomization to the date of death of the patient or to the last day of follow-up (censored).
Systemische therapie voorafgaand aan lokale behandeling leidt tot een betere overleving dan directe lokale behandeling bijpatiënten met lokaal behandelbare colorectale levermetastasen gerecidiveerd na eerdere lokaal behandelde levermetastasen. De primaire uitkomstmaat is algehele overleving.
E.2.2Secondary objectives of the trial
Main secondary endpoints are overall distant progression-free survival (DPFS), local tumor progression-free survival (LTPFS),systemic therapy related toxicity, procedural morbidity and mortality, length of hospital stay, assessment of pain and quality of life(QoL), cost-effectiveness ratio (ICER) and quality-adjusted life years (QALY).
Secundaire uitkomstmaten zijn progressie vrije overleving op afstand (DPFS), lokale progressie vrije overleving (LTPFS). Daarnaastwordt gekeken naar toxiciteit van systemische therapie, morbiditeit en mortaliteit van de ingrepen, lengte van ziekenhuisopname,kwaliteit van leven, kosteneffectiviteit en quality-adjusted life years (QALY’s).
E.2.3Trial contains a sub-study No
E.3Principal inclusion criteria
- Histological documentation of primary colorectal tumor
- Local treatment performed for initial CRLM
- ≥1 locally treatable recurrent CRLM (partial hepatectomy and/or thermal ablation)
- Resection for resectable lesions considered possible obtaining negative resection margins (R0) and preservingadequate liver reserve
- Total number of new CRLM ≤ 5
- No microsatellite instability (MSI)
- Good performance status (ECOG 0-2) // ASA 1-3
- No extrahepatic disease
- Both chemo-naïve patients and patients who did not progress on either CAPOX, FOLFOX, or FOLFIRIchemotherapy prior to the initial local treatment
- Patiënten met dikke darm- of endeldarmkanker én recidief uitzaaiingen in de lever binnen 1 jaar na eerderebehandeling van leveruitzaaiingen;.
- Patiënten zijn 18 jaar en ouder;
- Patiënten hebben voldoende algemene lichamelijke conditie;
- Patiënten zijn of worden tijdens het onderzoek niet zwanger;
- Er mag geen sprake zijn van uitzaaiingen buiten de lever ;
- Er mogen niet meer dan 5 recidief uitzaaiingen zijn ;
- Patiënten hebben of nog geen chemotherapie gehad als behandeling of in het verleden goede reactie gehad opde chemotherapie.
E.4Principal exclusion criteria
- Pregnant or breast-feeding subjects. Women of childbearing potential must have a negative pregnancy testperformed within 7 days of the start of treatment;
- Immunotherapy ≤ 6 weeks prior to the randomization;
- Chemotherapy ≤ 6 weeks prior to the randomization;
- Progression on both oxaliplatin and irinotecan;
- Severe allergy to contrast media not controlled with premedication.
- Zwangerschap of borstvoeding.
- Immunotherapie ≤ 6 weken voorafgaand aan de procedure;
- Chemotherapie ≤ 6 weken voorafgaand aan de;
- Progressie onder oxaliplatin en irinotecan;
- Contrastallergie welke niet-controleerbaar is met medicijnen.
E.5 End points
E.5.1Primary end point(s)
Primary study parameters/outcome of the study:
Primary objective is to compare overall survival (OS) in both study arms, counting from the date of randomization to the date ofdeath of the patient or to the last day of follow-up (censored).
Primaire onderzoeksvariabelen/uitkomstmaten:
De primaire uitkomstmaat is algehele overleving.
E.5.1.1Timepoint(s) of evaluation of this end point
Follow-up: Follow up after repeat local treatment is scheduled conform current guidelines:
3/4-montly in the first year, 6-monlty in the 2nd and 3rd year and 12-monlty in the 4th and 5th year.

The following parameters will be assessed at the follow up appointments3/4-monthly in the first year, 6-monthly in the 2nd & 3rd year and 12 monthly in the 4th &5th year:
-Laboratory tests including tumor markers (CEA; carcinoembryonic antigen)
-Cross-sectional imaging (ceCT or ceMRI; including DWI; diffusion-weighted imaging)
-Quality of life questionnaires (in addition, assessed prior to, during and after neoadjuvant systemic therapy; timeframe of 2 months around each follow-up moment)
Follow-up: Follow-up na herhaalde lokale behandeling wordt gepland volgens de huidige richtlijnen:
3/4-maandelijks in het eerste jaar, 6-maandelijks in het 2e en 3e jaar en 12-maandelijks in het 4e en 5e jaar.

De volgende parameters zullen worden beoordeeld tijdens de vervolgafspraken: 3/4-maandelijks in het eerste jaar, 6-maandelijks in het 2e en 3e jaar en 12-maandelijks in het 4e en 5e jaar:
- Laboratoriumtesten inclusief tumormarkers (CEA; carcino-embryonaal antigeen)
- Transversale beeldvorming (ceCT of ceMRI; inclusief DWI; diffusie-gewogen beeldvorming)
- Vragenlijsten over levenskwaliteit (bovendien beoordeeld vóór, tijdens en na neoadjuvante systemische therapie; tijdsbestek van 2 maanden rond elk follow-upmoment)
E.5.2Secondary end point(s)
Secundary study parameters/outcome of the study:
Main secondary endpoints are overall distant progression-free survival (DPFS), local tumor progression-free survival (LTPFS),systemic therapy related toxicity, procedural morbidity and mortality, length of hospital stay, assessment of pain and quality of life(QoL), cost-effectiveness ratio (ICER) and quality-adjusted life years (QALY).
Secundaire onderzoeksvariabelen/uitkomstmaten:
Secundaire uitkomstmaten zijn progressie vrije overleving op afstand (DPFS), lokale progressie vrije overleving (LTPFS). Daarnaastwordt gekeken naar toxiciteit van systemische therapie, morbiditeit en mortaliteit van de ingrepen, lengte van ziekenhuisopname,kwaliteit van leven, kosteneffectiviteit en quality-adjusted life years (QALY’s).
E.5.2.1Timepoint(s) of evaluation of this end point
See above.
Zie bovenstaand.
E.6 and E.7 Scope of the trial
E.6Scope of the trial
E.6.1Diagnosis No
E.6.2Prophylaxis No
E.6.3Therapy Yes
E.6.4Safety No
E.6.5Efficacy Yes
E.6.6Pharmacokinetic No
E.6.7Pharmacodynamic No
E.6.8Bioequivalence No
E.6.9Dose response No
E.6.10Pharmacogenetic No
E.6.11Pharmacogenomic No
E.6.12Pharmacoeconomic No
E.6.13Others No
E.7Trial type and phase
E.7.1Human pharmacology (Phase I) No
E.7.1.1First administration to humans No
E.7.1.2Bioequivalence study No
E.7.1.3Other No
E.7.1.3.1Other trial type description
E.7.2Therapeutic exploratory (Phase II) No
E.7.3Therapeutic confirmatory (Phase III) Yes
E.7.4Therapeutic use (Phase IV) No
E.8 Design of the trial
E.8.1Controlled Yes
E.8.1.1Randomised Yes
E.8.1.2Open Yes
E.8.1.3Single blind No
E.8.1.4Double blind No
E.8.1.5Parallel group No
E.8.1.6Cross over No
E.8.1.7Other No
E.8.2 Comparator of controlled trial
E.8.2.1Other medicinal product(s) No
E.8.2.2Placebo No
E.8.2.3Other Yes
E.8.2.3.1Comparator description
Lokale behandeling (chirurgische resectie en/of thermale ablatie)
Local treatment (surgical resection and/or thermal ablation)
E.8.2.4Number of treatment arms in the trial2
E.8.3 The trial involves single site in the Member State concerned No
E.8.4 The trial involves multiple sites in the Member State concerned Yes
E.8.4.1Number of sites anticipated in Member State concerned4
E.8.5The trial involves multiple Member States No
E.8.6 Trial involving sites outside the EEA
E.8.6.1Trial being conducted both within and outside the EEA No
E.8.6.2Trial being conducted completely outside of the EEA No
E.8.7Trial has a data monitoring committee Yes
E.8.8 Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial
LVLS
LVLS
E.8.9 Initial estimate of the duration of the trial
E.8.9.1In the Member State concerned years4
E.8.9.1In the Member State concerned months0
E.8.9.1In the Member State concerned days0
F. Population of Trial Subjects
F.1 Age Range
F.1.1Trial has subjects under 18 No
F.1.1.1In Utero No
F.1.1.2Preterm newborn infants (up to gestational age < 37 weeks) No
F.1.1.3Newborns (0-27 days) No
F.1.1.4Infants and toddlers (28 days-23 months) No
F.1.1.5Children (2-11years) No
F.1.1.6Adolescents (12-17 years) No
F.1.2Adults (18-64 years) Yes
F.1.2.1Number of subjects for this age range: 180
F.1.3Elderly (>=65 years) Yes
F.1.3.1Number of subjects for this age range: 180
F.2 Gender
F.2.1Female Yes
F.2.2Male Yes
F.3 Group of trial subjects
F.3.1Healthy volunteers No
F.3.2Patients Yes
F.3.3Specific vulnerable populations No
F.3.3.1Women of childbearing potential not using contraception No
F.3.3.2Women of child-bearing potential using contraception No
F.3.3.3Pregnant women No
F.3.3.4Nursing women No
F.3.3.5Emergency situation No
F.3.3.6Subjects incapable of giving consent personally No
F.3.3.7Others No
F.4 Planned number of subjects to be included
F.4.1In the member state360
F.5 Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)
After treatment in trial the patient can return to normal standard of care in consultation with their treating physician with standard follow-up regimens.
Na afloop van de studie of uitval uit de studie om welke reden dan ook kan de patient terugvallen op de normale zorg en behandeling bij zijn/haar behandelend arts en in standaard follow-up schema volgens de richtlijnen.
G. Investigator Networks to be involved in the Trial
N. Review by the Competent Authority or Ethics Committee in the country concerned
N.Competent Authority Decision Authorised
N.Date of Competent Authority Decision2023-04-24
N.Ethics Committee Opinion of the trial applicationFavourable
N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
N.Date of Ethics Committee Opinion2023-02-21
P. End of Trial
P.End of Trial StatusOngoing

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