Clinical Trials Register

Summary
EudraCT Number:	2014-002794-11
Sponsor's Protocol Code Number:	NL49960.018.14
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:	2014-09-01
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

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A. Protocol Information

A.1

Member State Concerned

Netherlands - Competent Authority

A.2

EudraCT number

2014-002794-11

A.3

Full title of the trial

Adjuvant hyperthermic intraperitoneal chemotherapy in patients with colon cancer at high risk of peritoneal carcinomatosis; the COLOPEC randomized multicenter trial

Adjuvante hypertherme intraperitoneale chemotherapie bij patiënten met een colon carcinoom en een hoog risico op peritonitis carcinomatosa; de multicenter gerandomiseerde COLOPEC studie

A.3.1

Title of the trial for lay people, in easily understood, i.e. non-technical, language

Intraperitoneal hyperterm chemotherapy as adjuvant treatment to prevent peritoneal carcinomatosis of colorectal origin

Buikspoeling met warme chemotherapie in patiënten met een hoog risico op uitzaaiingen van een dikke darm tumor naar het buikvlies

A.3.2

Name or abbreviated title of the trial where available

COLOPEC

A.4.1

Sponsor's protocol code number

NL49960.018.14

A.7

Trial is part of a Paediatric Investigation Plan

A.8

EMA Decision number of Paediatric Investigation Plan

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	Academic Medical Center
B.1.3.4	Country	Netherlands
B.3.1 and B.3.2	Status of the sponsor	Non-Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	ZonMw (CVZ)
B.4.2	Country	Netherlands
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Academic Medical Center
B.5.2	Functional name of contact point	Pieter Tanis
B.5.3	Address:
B.5.3.1	Street Address	Meibergdreef 9
B.5.3.2	Town/ city	Amsterdam
B.5.3.3	Post code	1105 AZ
B.5.3.4	Country	Netherlands
B.5.4	Telephone number	00310205669111
B.5.6	E-mail	P.J.Tanis@amc.nl

D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	Yes
D.2.1.1.1	Trade name	Oxaliplatine
D.2.1.1.2	Name of the Marketing Authorisation holder	sanofi-aventis Netherlands B.V.
D.2.1.2	Country which granted the Marketing Authorisation	Netherlands
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	oxaliplatin
D.3.4	Pharmaceutical form	Concentrate and solvent for solution for infusion
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intraperitoneal use
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No
D.IMP: 2
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	Yes
D.2.1.1.1	Trade name	Rescuvolin
D.2.1.1.2	Name of the Marketing Authorisation holder	Sandoz B.V.
D.2.1.2	Country which granted the Marketing Authorisation	Netherlands
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	Leucovorin
D.3.4	Pharmaceutical form	Solution for injection
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intravenous drip use (Noncurrent)
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No
D.IMP: 3
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	Yes
D.2.1.1.1	Trade name	5-fluorouracil
D.2.1.1.2	Name of the Marketing Authorisation holder	Sandoz B.V.
D.2.1.2	Country which granted the Marketing Authorisation	Netherlands
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	5-fluorouracil
D.3.4	Pharmaceutical form	Concentrate for solution for injection/infusion
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intravenous drip use (Noncurrent)
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another 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.1.1

Medical condition(s) being investigated

Adjuvant hyperthermic intraperitoneal chemotherapy in patients with colon cancer at high risk of peritoneal carcinomatosis; the COLOPEC randomized multicenter trial

Adjuvante hypertherme intraperitoneale chemotherapie bij patiënten met een colon carcinoom en een hoog risico op peritonitis carcinomatosa; de multicenter gerandomiseerde COLOPEC studie

E.1.1.1

Medical condition in easily understood language

colon cancer
peritoneal carcinomatosis

colon carcinoom
peritonitis carcinomatosa

E.1.1.2

Therapeutic area

Diseases [C] - Cancer [C04]

MedDRA Classification

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

The aim is to determine the effectiveness of adjuvant HIPEC using oxaliplatin following a curative resection of a pT4 or intra-abdominally perforated CRC in preventing the development of PC in comparison to the standard adjuvant systemic treatment

Het doel van het onderzoek is om de effectiviteit te bepalen van adjuvante HIPEC met oxaliplatin in het voorkomen van peritonitis carcinomatosa in verglijking met de standaard adjuvante chemotherapie in patienten die een curatieve resectie hebben ondergaan van een pT4 of een intra-abdominaal geperforeerde colorectaal carcinoom

E.2.2

Secondary objectives of the trial

Secondary endpoints are treatment related toxicity, incidence of PC, sensitivity of imaging to detect PC during follow-up, differences in patterns of dissemination (peritoneal plus or minus distant metastases), disease-free survival, overall survival, quality of life and costs.

Behandeling gerelateerde toxcitieit, incidenite van peritonitis carcinomatosa, senisitiviteit en specificiteit van de beeldvorming tijdens follow-up voor detectie van PC, ziekte vrije overleving, totale overleving, kwaliteit van leven en kosten

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

(1) age between 18 and 75 years. (2) adequate clinical condition to undergo re-laparoscopy or re-laparotomy within either 10 days or between week 5-8 from primary resection. (3) written informed consent (4) white blood cell count at least 3000/mm3, platelet count at least 100.000/mm3. (5) no bleeding diathesis or coagulopathy. (6) creatinine normal or creatinine clearance at least 50 ml/min.

(1) Leeftijd tussen 18 en 75 jaar. (2) De klinische conditie van de patient is goed genoeg om een relaparotomie danwel relaparoscopie binnen 10 dagen of tussen 5-8 weken naar primaire resectie te ondergaan. (3) Ingevuld toestemmingsformulier. (4) Serologische witte bloedcel aantal van minimaal 3000/mm3 en een serologische bloedplaatjes aantal van minimaal 100.000/mm3. (5) geen hemorragische diathese dan wel coagulopathy. (6) serologische creatine waarde of een creatinine klaring van minimaal 50 ml/min.

E.4

Principal exclusion criteria

(1) postoperative complications that interfere with adjuvant HIPEC within 8 weeks (i.e. persisting intra-abdominal abscess, significant fascial dehiscence, enteric fistula). (2) liver and/or lung metastases. (3) pregnant or lactating women. (4) unstable or uncompensated respiratory or cardiac disease. (5) serious active infections. (6) other concurrent chemotherapy. (7) hypersensitivity for fluorouracil folinic acid (calciumfolinate) or another substance of leucovorin or Oxaliplatin. (8) Stomatitis, ulceration in the mouth or gastrointestinal tract. (9) severe diarrhea (10) severe hepatic and / or renal dysfunction. (11) plasma bilirubin concentrations greater than 85 μmol/l. (12) Pernicious anemia or other anaemias due to vitamin B12 deficiency.(13) peripheral sensory neuropathy with functional impairment.

(1) postoperative complicaties die adjuvante HIPEC binnen 8 weken onmogelijk maken ( b.v. persisterend intra-abdominaal abces, persisterende fasciedehiscentie, of darmfistel). (2) lever en/of long metastasen. (3) zwangeren of lacterende vrouwen. (4) instabiele of gedeompenseerde respiratoire of cardiale ziektes. (5) ernstige actieve infecties. (6) andere gelijktijdige chemotherapie. (7) overgevoeligheid voor fluorouracil voor folinezuur (calciumfolinaat) of voor één van de bestanddelen van leucovorin of oxaliplatine. (8) stomatitis, ulceraties in de mond en het maagdarmkanaal (9) ernstige diarree (10) sterk verminderde lever- en/of nierfunctie (11) bilirubineplasmaconcentratie hoger dan 85 μmol/l. (12) Pernicieuze anemie of andere anemieën als gevolg van een tekort aan vitamine B12. (13) een perifere sensore neuropathie met functieverlies.

E.5 End points

E.5.1

Primary end point(s)

Primary endpoint is peritoneal recurrence-free survival at 18 months.

Peritoneaal recidief vrije overleving 18 maanden na de primaire resectie

E.5.1.1

Timepoint(s) of evaluation of this end point

18 months

18 maanden

E.5.2

Secondary end point(s)

• Treatment related toxicity, including 30-day complication rate and re-admission rate
• Hospital stay
• Incidence of Peritonis carcinomatosa (PC)
• Sensitivity of imaging to detect PC during follow-up
• Differences in patterns of dissemination (peritoneal plus or minus distant metastases)
• Disease-free survival
• Overall survival
• Quality of life
• Costs
• PC during diagnostic laparoscopy at 18 months

• Behandeling gerelateerde toxiciteit, inclusie 30 dagen complicaties en heropname
• ziekenhuisverblijf
• Incidentie van peritonitis carcinomatosa (PC)
• Sensitiviteit van beeldvorming tjidens follow-up
• verschillen in dissiminatie patronen ( Peritoneum plus of min afstandsmetastasen)
• Ziekte vrije overlevin
• totale overleving
• kwaliteit van leven
• kosten
• PC tijdens diagnostische laparoscopie

E.5.2.1

Timepoint(s) of evaluation of this end point

3, 6, 12, 18, 24, 36, 48 and 60 months

3, 6, 12, 18, 24, 36, 48 en 60 maanden

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

Yes

E.6.2

Prophylaxis

Yes

E.6.3

Therapy

Yes

E.6.4

Safety

Yes

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

E.6.7

Pharmacodynamic

E.6.8

Bioequivalence

E.6.9

Dose response

E.6.10

Pharmacogenetic

E.6.11

Pharmacogenomic

E.6.12

Pharmacoeconomic

E.6.13

Others

E.7

Trial type and phase

E.7.1

Human pharmacology (Phase I)

E.7.1.1

First administration to humans

E.7.1.2

Bioequivalence study

E.7.1.3

Other

E.7.1.3.1

Other trial type description

E.7.2

Therapeutic exploratory (Phase II)

E.7.3

Therapeutic confirmatory (Phase III)

Yes

E.7.4

Therapeutic use (Phase IV)

E.8 Design of the trial

E.8.1

Controlled

Yes

E.8.1.1

Randomised

Yes

E.8.1.2

Open

Yes

E.8.1.3

Single blind

E.8.1.4

Double blind

E.8.1.5

Parallel group

Yes

E.8.1.6

Cross over

E.8.1.7

Other

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

Yes

E.8.2.2

Placebo

E.8.2.3

Other

Yes

E.8.2.3.1

Comparator description

de standaard behandeling namelijk adjuvante chemohterapie

Standard adjuvant chemotherapy

E.8.2.4

Number of treatment arms in the trial

E.8.3

The trial involves single site in the Member State concerned

E.8.4

The trial involves multiple sites in the Member State concerned

Yes

E.8.4.1

Number of sites anticipated in Member State concerned

E.8.5

The trial involves multiple Member States

Yes

E.8.5.1

Number of sites anticipated in the EEA

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

E.8.6.2

Trial being conducted completely outside of the EEA

E.8.7

Trial 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

The trial will be completed at 60 months or will be terminated if a serious treatment-related adverse event occurs, making it impossible to recruit new patients or to continue the treatment of patients already recruited for medical or ethical reasons.

The gehele studie is voltooid na 60 maanden. Tevens wordt de studie beeindigt als er een serieuse behandeling gerelateerde uitkomst optreed, wat het onmolgeijk maakt om nieuwe patienten te includeren of om de behandeling te continueren in patienten die al behandeld worden of om medische dan wel ethische redenen.

E.8.9 Initial estimate of the duration of the trial

E.8.9.1

In the Member State concerned years

E.8.9.1

In the Member State concerned months

E.8.9.1

In the Member State concerned days

E.8.9.2

In all countries concerned by the trial years

E.8.9.2

In all countries concerned by the trial months

E.8.9.2

In all countries concerned by the trial days

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

F.1.1.1

In Utero

F.1.1.2

Preterm newborn infants (up to gestational age < 37 weeks)

F.1.1.3

Newborns (0-27 days)

F.1.1.4

Infants and toddlers (28 days-23 months)

F.1.1.5

Children (2-11years)

F.1.1.6

Adolescents (12-17 years)

F.1.2

Adults (18-64 years)

Yes

F.1.2.1

Number of subjects for this age range:

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

158

F.2 Gender

F.2.1

Female

Yes

F.2.2

Male

Yes

F.3 Group of trial subjects

F.3.1

Healthy volunteers

F.3.2

Patients

Yes

F.3.3

Specific vulnerable populations

F.3.3.1

Women of childbearing potential not using contraception

F.3.3.2

Women of child-bearing potential using contraception

F.3.3.3

Pregnant women

F.3.3.4

Nursing women

F.3.3.5

Emergency situation

F.3.3.6

Subjects incapable of giving consent personally

F.3.3.7

Others

F.4 Planned number of subjects to be included

F.4.1

In the member state

176

F.4.2

For a multinational trial

F.4.2.1

In the EEA

176

F.4.2.2

In the whole clinical trial

176

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)

Regular standard treatment follow-up (oncoline.nl)

De reguliere follow-up ( oncoline.nl)

G. Investigator Networks to be involved in the Trial
G.4 Investigator Network to be involved in the Trial: 1

N. Review by the Competent Authority or Ethics Committee in the country concerned

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2014-09-01

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2014-12-08

P. End of Trial
P.	End of Trial Status	Ongoing

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