Clinical Trials Register

Summary
EudraCT Number:	2021-005465-41
Sponsor's Protocol Code Number:	CERVANTES
National Competent Authority:	Czechia - SUKL
Clinical Trial Type:	EEA CTA
Trial Status:	Trial now transitioned
Date on which this record was first entered in the EudraCT database:	2021-11-10
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

Czechia - SUKL

A.2

EudraCT number

2021-005465-41

A.3

Full title of the trial

An international randomised trial of radical surgery followed by adjuvant (chemo)radiation versus no further treatment in patients with early-stage, intermediate-risk cervical cancer patients

Role radikální chirurgie a adjuvantní (chemo)radioterapie v léčbě pacientek s časným stádiem a středním rizikem karcinomu děložního hrdla. Prospektivní multicentrická mezinárodní studie.

A.3.1

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

Intermediate risk carvical cancer: radical surgery +/- adjuvant radiotherapy

Karcinom děložního hrdla středního rizika: role radikální chirurgie a adjuvantní (chemo)radioterapie

A.4.1

Sponsor's protocol code number

CERVANTES

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	CEEGOG reg. ass.
B.1.3.4	Country	Czechia
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	CEEGOG reg.ass
B.4.2	Country	Czechia
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	CEEGOG reg. ass.
B.5.2	Functional name of contact point	prof. MUDr. David Cibula, Ph.D.
B.5.3	Address:
B.5.3.1	Street Address	Apolinarska 18
B.5.3.2	Town/ city	Praha 2
B.5.3.3	Post code	128 51
B.5.3.4	Country	Czechia
B.5.4	Telephone number	00420224967451
B.5.6	E-mail	dc@davidcibula.cz

D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3	IMP Role	Comparator
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.2.1.2	Country which granted the Marketing Authorisation	European Union
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	Cisplatin
D.3.4	Pharmaceutical form	Concentrate for solution for infusion
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intravenous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Cisplatin
D.3.9.1	CAS number	15663-27-1
D.3.9.4	EV Substance Code	SUB07483MIG
D.3.10	Strength
D.3.10.1	Concentration unit	mg/ml milligram(s)/millilitre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	1
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	Comparator
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.2.1.2	Country which granted the Marketing Authorisation	European Union
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	Carboplatin
D.3.4	Pharmaceutical form	Concentrate for solution for infusion
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intravenous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Carboplatin
D.3.9.1	CAS number	41575-94-4
D.3.9.4	EV Substance Code	SUB06614MIG
D.3.10	Strength
D.3.10.1	Concentration unit	mg/ml milligram(s)/millilitre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	10
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

early-stage, intermediate-risk cervical cancer patients

E.1.1.1

Medical condition in easily understood language

Cervical cancer

E.1.1.2

Therapeutic area

Diseases [C] - Cancer [C04]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	21.1
E.1.2	Level	PT
E.1.2	Classification code	10008342
E.1.2	Term	Cervix carcinoma
E.1.2	System Organ Class	10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)

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 objective of the trial is to evaluate if adjuvant (chemo)radiation is associated with disease free survival benefit after radical surgery in patients with intermediate-risk cervical cancer. The intermediate-risk group is defined as lymph-node negative patients (N0) with a combination of tumour-related negative prognostic risk factors

E.2.2

Secondary objectives of the trial

The key secondary objective is to compare the overall survival benefit between both trial ARMs.
Further secondary objectives are assessment of pelvic disease-free survival, health-related quality of life assessed by patients reported outcome questionnaires, and differences between both arms in prevalence and severity of treatment-related adverse events assessed according to Common Terminology Criteria for Adverse Events v5.0 (CTCAE v5.0).

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

Inclusion criteria
Preoperative inclusion criteria upon trial registration
1. Age 18–85 years
2. Pathologically confirmed invasive cervical cancer
3. FIGO IB1-IIA (APPENDIX D)
4. Squamous cell cancer or HPV-related adenocarcinoma
5. Presence of tumour-related risk factors as follows:
a. tumour ≥4 cm OR
b. tumour >2 cm <4 cm AND LVSI OR
c. tumour >2 cm <4 cm AND TFD <3 mm OR
d. >2 cm <4 cm AND DSI >2/3
6. No evidence of enlarged or suspicious pelvic lymph nodes or distant metastases on imaging (by radiological subjective assessment)
7. Deemed suitable and fit for radical surgery followed by adjuvant radiotherapy*
*Concomitant chemotherapy is not considered a mandatory part of adjuvant management.
8. Negative HIV test (performed only in high-risk countries or patients who have moved from those countries within the past 10 years)
9. Negative pregnancy test (if applicable)
10. Informed consent form (ICF) signed by a patient
Post-operative inclusion criteria upon trial randomisation
1. Pathologically confirmed FIGO IB1-IIA (APPENDIX D)
2. Squamous cell cancer or usual type adenocarcinoma confirmed by final pathology
3. Cumulation of tumour-related risk factors as follows:
a. tumour ≥4 cm OR
b. tumour >2 cm <4 cm AND LVSI OR
c. tumour >2 cm <4 cm AND TFD <3 mm OR
d. tumour >2 cm <4 cm AND DSI >2/3
4. Negative parametria – negative parametrial LN and no continuous invasion from the cervix
5. Negative pelvic lymph nodes (SLN and all other pelvic LN from the final pathology)
6. Deemed suitable and fit for radical surgery followed by adjuvant radiotherapy*
*Concomitant chemotherapy is not considered a mandatory part of adjuvant management.

E.4

Principal exclusion criteria

Exclusion criteria
1. Adenosquamous cancer or adenocarcinoma unusual type (non-HPV related, such as: mucinous, clear cell, mesonephric) or another rare tumour types (those not listed in the inclusion criteria)
2. Inconclusive primary site of disease
3. Unequivocally enlarged LN by imaging (by radiological subjective assessment) or positive pelvic LN from final pathology*
* Applies to any type of metastasis: isolated tumour cells (ITC), micrometastasis (MIC), macrometastasis (MAC).
4. Positive surgical margins = R1; either parametria (positive LN or continuous invasion from the cervix) or vaginal cuff (invasive disease)
5. FIGO <IB1 / >IIA
6. Adequate type of surgery not performed (refer to 11.1. Radical surgery)
7. Previous pelvic malignancy
8. History of second primary cancer outside pelvis if ≤ 3 years CCR
9. Previous pelvic radiotherapy
10. Neoadjuvant chemotherapy prior surgical treatment
11. Confirmed pregnancy
12. HIV positivity
13. Low likelihood of patient compliance to the follow-up

E.5 End points

E.5.1

Primary end point(s)

Disease-free survival (DFS)– Calculated as an interval from the day of randomisation until diagnosis of recurrence: (a) unequivocal finding on imaging by subjective radiological assessment; b) suspicious recurrence on imaging or by physical examination either confirmed by biopsy or supported by other signs (disease progression on imaging or progression of symptoms); (c) death caused by disease or death of unknown cause.

E.5.1.1

Timepoint(s) of evaluation of this end point

Expected 3 years after the last patient is randomised.

E.5.2

Secondary end point(s)

a) Overall survival (OS)
b) Pelvic disease-free survival (PDFS)
c) Health-related quality of life (QoL)
d) Treatment-related adverse events

E.5.2.1

Timepoint(s) of evaluation of this end point

Secondary endpoints´ analyses are expected 6 years after randomisation of the last patient.

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

E.6.3

Therapy

Yes

E.6.4

Safety

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

Yes

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)

E.8.2.2

Placebo

E.8.2.3

Other

Yes

E.8.2.3.1

Comparator description

adjuvant treatment - chemo and/or radiotherapy treatment

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

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

Yes

E.8.6.2

Trial being conducted completely outside of the EEA

E.8.6.3

If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned

Belarus

Brazil

Canada

Colombia

Georgia

India

Peru

Ukraine

United States

Belgium

Croatia

Italy

Netherlands

Norway

Poland

Slovakia

Slovenia

Spain

Czechia

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

LPLV

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

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:

400

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

114

F.2 Gender

F.2.1

Female

Yes

F.2.2

Male

F.3 Group of trial subjects

F.3.1

Healthy volunteers

F.3.2

Patients

Yes

F.3.3

Specific vulnerable populations

Yes

F.3.3.1

Women of childbearing potential not using contraception

F.3.3.2

Women of child-bearing potential using contraception

Yes

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

150

F.4.2

For a multinational trial

F.4.2.1

In the EEA

264

F.4.2.2

In the whole clinical trial

514

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)

survival follow-up information

G. Investigator Networks to be involved in the Trial
G.4 Investigator Network to be involved in the Trial: 1
G.4.1	Name of Organisation	ENGOT
G.4.3.4	Network Country	Denmark

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

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2022-02-09

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2022-03-17

P. End of Trial
P.	End of Trial Status	Trial now transitioned

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