Clinical Trials Register

Summary
EudraCT Number:	2020-004494-41
Sponsor's Protocol Code Number:	CLIN2001UCM301
National Competent Authority:	Spain - AEMPS
Clinical Trial Type:	EEA CTA
Trial Status:	Ongoing
Date on which this record was first entered in the EudraCT database:	2023-01-16
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

Spain - AEMPS

A.2

EudraCT number

2020-004494-41

A.3

Full title of the trial

Multicenter Phase 3 Pivotal Study to Evaluate the Safety and Efficacy of TOOKAD (padeliporfin) Vascular Targeted Photodynamic Therapy in the Treatment of Low Grade Upper Tract Urothelial Cancer

Estudio fundamental, de fase 3, multicéntrico para evaluar la seguridad y la eficacia de la terapia fotodinámica focalizada vascular con TOOKAD (padeliporfina) en el tratamiento del cáncer urotelial de vías urinarias altas de grado bajo

A.3.1

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

This is a study that will evaluate the safety and efficacy of TOOKAD® (padeliporfin) Vascular Targeted Photodynamic Therapy (VTP) in the Treatment of Low Grade Upper Tract Urothelial Cancer (UTUC).

Este estudio evaluará la seguridad y eficacia de TOOKAD (padeliporfina) en el tratamiento del cáncer urotelial de vías urinarias altas de grado bajo

A.3.2

Name or abbreviated title of the trial where available

ENdoluminal LIGHT ActivatED Treatment of Upper Tract Urothelial Cancer (ENLIGHTED) Study

A.4.1

Sponsor's protocol code number

CLIN2001UCM301

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	Steba Biotech, S.A.
B.1.3.4	Country	Luxembourg
B.3.1 and B.3.2	Status of the sponsor	Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	Steba biotech, S.A.
B.4.2	Country	Luxembourg
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	STEBA biotech S.A.
B.5.2	Functional name of contact point	Head of Global R&D
B.5.3	Address:
B.5.3.1	Street Address	7 place du Théâtre
B.5.3.2	Town/ city	Luxembourg
B.5.3.3	Post code	L-2613
B.5.3.4	Country	Luxembourg
B.5.4	Telephone number	0043664203 4173
B.5.6	E-mail	d.perry@stebabiotech.com

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	TOOKAD®
D.2.1.1.2	Name of the Marketing Authorisation holder	Steba biotech S.A.
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.3.4	Pharmaceutical form	Powder for solution for injection
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	PADELIPORFIN
D.3.9.1	CAS number	886845-72-3
D.3.9.2	Current sponsor code	WST11
D.3.9.3	Other descriptive name	Palladium Bacteriopheophorbide Monolysotaurine
D.3.9.4	EV Substance Code	SUB31318
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	9.15
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	Yes
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

Low Grade Upper Tract Urothelial Cancer

Cáncer urotelial de vías urinarias altas de grado bajo

E.1.1.1

Medical condition in easily understood language

Urinary tract cancers

Cancer vías urinarias

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	LLT
E.1.2	Classification code	10077840
E.1.2	Term	Urothelial cancer of renal pelvis
E.1.2	System Organ Class	100000004864

E.1.2 Medical condition or disease under investigation

E.1.2	Version	20.0
E.1.2	Level	LLT
E.1.2	Classification code	10046375
E.1.2	Term	Ureter cancer
E.1.2	System Organ Class	100000004864

E.1.3

Condition being studied is a rare disease

Yes

E.2 Objective of the trial

E.2.1

Main objective of the trial

To demonstrate the efficacy and durability of effect following TOOKAD (padeliporfin) VTP on low grade UTUC tumors in the calyces, renal pelvis and ureter

Demostrar la eficacia y la perdurabilidad del efecto de la terapia VTP con TOOKAD (padeliporfina) en los tumores del CU-VUA bien diferenciado en los cálices, la pelvis renal y el uréter.

E.2.2

Secondary objectives of the trial

-To evaluate TOOKAD (padeliporfin) VTP related safety and tolerability in the treatment of low grade UTUC tumors in the calyces, renal pelvis and ureter
-To explore a potential link between UTUC cancer genomic markers and treatment related clinical outcomes and disease progression

- Evaluar la seguridad y la tolerabilidad relacionadas con la terapia VTP con TOOKAD (padeliporfina) en el tratamiento de los tumores del CU-VUA bien diferenciado en los cálices, la pelvis renal y el uréter.
- Investigar la posible relación entre los marcadores genómicos del CU-VUA y los resultados clínicos relacionados con el tratamiento y la progresión tumoral.

E.2.3

Trial contains a sub-study

Yes

E.2.3.1

Full title, date and version of each sub-study and their related objectives

-To evaluate the pharmacokinetic profile in UTUC patients with moderate hepatic impairment.

- Evaluar el perfil farmacocinético en los pacientes con CU-VUA que padecen insuficiencia hepática moderada.

E.3

Principal inclusion criteria

1.Male and female patients 18 years or older
2.Able to understand and provide written informed consent and willing to comply with all tests and procedures associated with the study
3.New or recurrent low-grade, non-invasive UTUC disease
4.Biopsy-proven disease. A concurrence of the central pathology reader will be required for eligibility.
5.Up to 2 biopsy-proven sites of low-grade involvement with the largest tumor (index tumor) between 5 mm and 15 mm in diameter (as measured by endoscopy), both located in the calyces, renal pelvis or in the ureter of ipsilateral kidney, with an absence of high-grade cells on cytology. (Ureter involvement should be in one anatomical location with no more than 20 mm of contiguous ureteral length).
6.Karnofsky Performance Status ≥ 50%
7.Adequate organ function defined at baseline as:
▪ANC ≥1,000/ μl,
▪Platelets ≥75,000/ μl, Hb ≥9 g/dl,
▪INR ≤2
▪Estimated glomerular filtration rate eGFR ≥30 ml/min using CKD-EPI Method
▪Total serum bilirubin <3 mg/dL, AST/ALT ≤5× upper limit of normal

1. Pacientes de ambos sexos de al menos 18 años.
2. Capacidad para comprender y otorgar el consentimiento informado por escrito, y disposición a someterse a todas las pruebas y procedimientos relacionados con el estudio.
3. CU-VUA no infiltrante bien diferenciado nuevo o recidivante.
4. Enfermedad demostrada por biopsia. Se exigirá la conformidad del evaluador central de anatomía patológica para determinar la idoneidad.
5. Hasta dos focos de afectación tumoral de bajo grado de diferenciación confirmados mediante biopsia con el tumor de mayor tamaño (tumor de referencia) de entre 5 mm y 15 mm de diámetro (medido mediante endoscopia), ambos localizados en los cálices, la pelvis renal o el uréter del riñón ipsilateral, con ausencia de células tumorales poco diferenciadas en la citología. (La afectación del uréter debe estar en una localización anatómica con una longitud ureteral contigua no superior a 20 mm).
6. Estado funcional de Karnofsky del ≥50 %.
7. Función orgánica adecuada definida en el momento basal como sigue:
■ CAN ≥1000/μl
■ Plaquetas ≥75 000/μl, Hb 9 g/dl
■ INR ≤2
■ Filtración glomerular estimada (FGe) ≥30 ml/min (con el método CKD-EPI, referencia 13 y apéndice 4)
■ Bilirrubina sérica total <3 mg/dl, AST/ALT ≤5 veces el límite superior de la normalidad

E.4

Principal exclusion criteria

1.Current high-grade or muscle invasive (>pT1) urothelial carcinoma of the bladder
2.Carcinoma in situ (CIS) current or previous in the upper urinary tract
3.History of invasive T2 or higher urothelial cancer in past 2 years
4.Participation in another clinical study involving an investigational product within 1 month before study entry
5.BCG or local chemotherapy treatment (including VEGF-targeted therapy) in the upper urinary tract within 2 months prior to inclusion
6.Systemic chemotherapy treatment (including VEGF-targeted therapy) within 2 months prior to enrollment
7.Prohibited medication that could not be adjusted or discontinued prior to study treatment
8. Patients with photosensitive skin diseases or porphyria
9.Any other medical or psychiatric co-morbidities, including decompensated heart failure, unstable angina or coronary artery disease, severe pulmonary or liver disease or current heavy smoker that, in the opinion of the study investigator, would make the patient a poor candidate for the study
10.Pregnant or breast-feeding women
Women of childbearing potential (WOCBP) must undergo a negative serum pregnancy test prior to study entry.
11.Men and women of reproductive potential not willing to observe conventional and effective birth control for the duration of treatment and for 90 days following the last TOOKAD VTP treatment

1. Presentar en la actualidad un carcinoma urotelial de vejiga (>pT1) con infiltración muscular o poco diferenciado.
2. Presentar en la actualidad o tener antecedentes de carcinoma in situ (CIS) en las vías urinarias altas.
3. Haber tenido carcinoma urotelial infiltrante T2 o mayor en los 2 últimos años.
4. Haber participado en otro estudio clínico de un producto en investigación en el mes previo a la incorporación al estudio.
5. Haber recibido tratamiento con BCG o quimioterapia local (incluido el tratamiento dirigido al VEGF) en las vías urinarias altas en los 2 meses previos a la inclusión.
6. Haber recibido quimioterapia sistémica (incluido el tratamiento dirigido al VEGF) en los 2 meses previos a la inclusión.
7. Estar en tratamiento con medicamentos prohibidos que no pudieron ajustarse o suspenderse antes de recibir el tratamiento del estudio (véanse la lista del apéndice 3 y las indicaciones del apartado 11.4.4).
8. Presentar dermatosis fotosensible o porfiria.
9. Presentar cualquier otro trastorno médico o psiquiátrico concomitante, como insuficiencia cardíaca descompensada, angina inestable, arteriopatía coronaria, neumopatía o hepatopatía graves o ser un gran fumador, que, en opinión del investigador del estudio, haría que el paciente no fuese un buen candidato para participar en el estudio.
10. Estar embarazada o en período de lactancia.
• Las mujeres con capacidad de procrear (MCCP) deberán dar negativo en la prueba de embarazo en suero realizada antes de incorporarse al estudio.
11. Los varones y las mujeres con capacidad de procrear que no estén dispuestos a utilizar un método anticonceptivo habitual y eficaz durante el tratamiento del estudio y hasta 90 días después del último tratamiento VTP con TOOKAD.

E.5 End points

E.5.1

Primary end point(s)

The primary efficacy outcome is the absence of UTUC tumors in the entire ipsilateral calyces, renal pelvis and ureter on endoscopic evaluation. This outcome will be determined dichotomously as either failure or success in achieving complete response.

Complete Response will be defined as absence of disease based on:
•absence of visual tumor on endoscopy
•no evidence of tumor on biopsy (if feasible)
•negative urinary cytology by instrumented collection

Additional information are part of the protocol (section Primary Endpoint/Estimand)

El criterio de valoración principal de la eficacia es la ausencia de tumores del CU-VUA en todos los cálices, la pelvis renal y el uréter ipsilaterales en la exploración endoscópica. Esta variable se determinará de forma dicotómica como fracaso o éxito en la consecución de una respuesta completa.

La respuesta completa se definirá como la ausencia de enfermedad según lo siguiente:

• Ausencia de tumores visibles en la endoscopia.
• Ausencia de signos tumorales en la biopsia (si es posible).
• Resultado negativo en la citología urinaria realizada con muestras extraídas mediante instrumental.

En el protocolo se incluye información adicional (section Primary Endpoint/Estimand) .

E.5.1.1

Timepoint(s) of evaluation of this end point

This endpoint will be evaluated at the time of Primary Response Evaluation (PRE) (28 +/- 3 days post last treatment) during the TOOKAD (padeliporfin) VTP induction treatment phase.

Este criterio se evaluará en el momento de la evaluación principal de la respuesta (EPR) (28 +/–3 días después del último tratamiento) en la fase de tratamiento de inducción con terapia VTP con TOOKAD (padeliporfina).

E.5.2

Secondary end point(s)

1.The duration of response at the entire ipsilateral kidney will be defined as absence of disease in the entire ipsilateral calyces, renal pelvis and ureter
2.The duration of response at the Treatment Area of the ipsilateral kidney will be defined as absence of disease in the ipsilateral Treatment Area
3.Overall renal functional outcome
4.Kidney organ loss or preservation
5.Pathological evaluation of response performed in kidney tissue of patient that will undergo kidney surgical removal following at least ne TOOKAD VTP treatment
6.Safety follow up based and recording of adverse events

Additional information are part of the protocol (section secondary Endpoint/Estimands)

1. La duración de la respuesta en todo el riñón ipsilateral se definirá como la ausencia de tumores en todos los cálices, la pelvis renal y el uréter ipsilaterales
2. La duración de la respuesta en la zona de tratamiento del riñón ipsilateral se definirá como la ausencia de enfermedad en la zona de tratamiento ipsilateral
3. Resultado de la evaluación de la función renal.
4. La extirpación o conservación del riñón.
5. Evaluación anatomopatológica de la respuesta en el tejido renal de los pacientes que se sometan a una extirpación quirúrgica del riñón después de al menos un tratamiento VTP con TOOKAD.
6. Seguimiento de la seguridad y registro de los acontecimientos adversos.

En el protocolo se incluye información adicional (section secondary Endpoint/Estimands).

E.5.2.1

Timepoint(s) of evaluation of this end point

1.Measured at the 3, 6, 9, 12, 18, 24, 36, 48, and 60 months post PRE
2.Measured at the 3, 6, 9, 12, 18, 24, 36, 48, and 60 months post PRE
3.Measured at the 6, 12, 18, 24, 36, 48, and 60 months post PRE
4.Measured at the 3, 6, 9, 12, 18, 24, 36, 48, and 60 months post PRE
5.Whenever possible for patients that will undergo kidney surgical removal post PRE
6. Safety at 3, 6, 9, 12, 18, 24, 36, 48, and 60 months post PRE
Timepoints at 18 ,24 36, 48 and 60 month months post PRE for patients who have a CR in at the end of maintenance treatment phase or 6 and 12 months post PRE if the patient has not participated to Maintenance treatment phase or 6 and 12 months post last VTP for patient discontinued from the treatment phases.

1. Se analizará a l s 3,6,9,12,18,24,36,48 y 60 meses después de la EPR.
2. Se analizará a los 3,6,9,12,18,24,36,48 y 60 meses después de la EPR.
3. Se analizará a los 6,12,18,24,36,48 y 60 meses después de la EPR.
4. Se analizará a los 3,6,9,12,18,24,36,48 y 60 meses después de la EPR.
5. Cuando sea posible pacientes que se sometan a una extirpación quirúrgica del riñón después de la EPR.
6. Seguridad a los 3,6,9,12,18,24,36,48 y 60 meses después de la EPR.
Puntos temporales a los 18,24,36,48 y 60 meses después de la EPR en los pacientes con RC en el fin de la fase de tto de mtto o a los 6 y 12 meses después de la EPR i los pacientes no han participado en la fase de tto de mtto o a los 6 y 12 meses despues de la ultima VTP por pacientes discontinuados de la fase de tto.

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

Yes

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

Yes

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

Yes

E.6.13.1

Other scope of the trial description

Tumour genomic

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

E.8.1.1

Randomised

E.8.1.2

Open

Yes

E.8.1.3

Single blind

E.8.1.4

Double blind

E.8.1.5

Parallel group

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)

Information not present in EudraCT

E.8.2.2

Placebo

Information not present in EudraCT

E.8.2.3

Other

Information not present in EudraCT

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

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

Israel

United States

Austria

France

Spain

Germany

Italy

United Kingdom

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

LVLS

UVUP

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

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:

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

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

F.4.2

For a multinational trial

F.4.2.1

In the EEA

F.4.2.2

In the whole clinical trial

100

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 the trial, the patient care will revert to their physicians

Despues del estudio, el cuidado del paciente volverá a su médico.

G. Investigator Networks to be involved in the Trial

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

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2023-04-12

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2023-01-12

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

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