Clinical Trials Register

Summary
EudraCT Number:	2022-003713-11
Sponsor's Protocol Code Number:	1938/2022
National Competent Authority:	Austria - BASG
Clinical Trial Type:	EEA CTA
Trial Status:	Ongoing
Date on which this record was first entered in the EudraCT database:	2023-01-31
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

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A. Protocol Information

A.1

Member State Concerned

Austria - BASG

A.2

EudraCT number

2022-003713-11

A.3

Full title of the trial

[177Lu]Lu-PSMAI&T radioligand therapy (PSMA-RLT) for patients with prostate cancer and biochemical but not radio-morphological local recurrence after primary therapy with curative intent: A Prospective Phase II Study

[177Lu]Lu-PSMAI&T-Radioligandentherapie (PSMA-RLT) bei Patienten mit Prostatakrebs und biochemischem, aber nicht radiomorphologischem Lokalrezidiv nach Primärtherapie mit kurativer Absicht: Eine prospektive Phase-II-Studie

A.3.1

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

[177Lu]Lu-PSMAI&T radioligand therapy (PSMA-RLT) in patients with prostate cancer and biochemical but not radiomorphologic local recurrence after primary therapy with curative intention: a future planned phase II study

A.3.2

Name or abbreviated title of the trial where available

PSMA-RLT in biochemically recurrent prostate cancer

PSMA-RLT bei biochemisch rezidivierendem Prostatakrebs.

A.4.1

Sponsor's protocol code number

1938/2022

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	Medical University of Vienna
B.1.3.4	Country	Austria
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	Medical University of Vienna
B.4.2	Country	Austria
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Medical University of Vienna
B.5.2	Functional name of contact point	Coordination Center-Clinical Study
B.5.3	Address:
B.5.3.1	Street Address	Währinger Straße 25a, Obergeschoß 1
B.5.3.2	Town/ city	Vienna
B.5.3.3	Post code	1090
B.5.3.4	Country	Austria
B.5.4	Telephone number	Öster140160-25176
B.5.5	Fax number	Öster140160-925180
B.5.6	E-mail	kks@meduniwien.ac.at
B.Sponsor: 2
B.1.1	Name of Sponsor	Medical University of Vienna
B.1.3.4	Country	Austria
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	Medical University of Vienna
B.4.2	Country	Austria
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Medical University of Vienna
B.5.2	Functional name of contact point	Coordination Center_Clinical Study
B.5.3	Address:
B.5.3.1	Street Address	Waehringer Straße 25a
B.5.3.2	Town/ city	Vienna
B.5.3.3	Post code	1090
B.5.3.4	Country	Austria
B.5.4	Telephone number	Öster140160-25176
B.5.5	Fax number	Öster140160-925180
B.5.6	E-mail	kks@meduniwien.ac.at

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	No
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	[177Lu]Lu-PSMA-I&T
D.3.4	Pharmaceutical form	Injection/infusion
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Solution for infusion (Noncurrent) Infusion (Noncurrent)
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	lutetium (177Lu) zadavotide guraxetan
D.3.9.1	CAS number	2447131-70-4
D.3.9.3	Other descriptive name	[177Lu]Lu-PSMA- I&T
D.3.9.4	EV Substance Code	SUB199344
D.3.10	Strength
D.3.10.1	Concentration unit	GBq gigabecquerel(s)
D.3.10.2	Concentration type	range
D.3.10.3	Concentration number	3 to 6
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	Yes
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

Prostate cancer

Prostatakrebs

E.1.1.1

Medical condition in easily understood language

Prostate cancer

Prostatakrebs

E.1.1.2

Therapeutic area

Diseases [C] - Male diseases of the urinary and reproductive systems [C12]

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

Primary objective:
• Evaluate the prostate specific antigen (PSA) response to [177Lu]Lu-PSMAI&T-RLT
• Assess therapy toxicity of systemic PSMA-RLT.

Primäre Ziele:
- Bewertung der Reaktion des prostataspezifischen Antigens (PSA) auf [177Lu]Lu-PSMAI&T-RLT
- Bewertung der Therapietoxizität der systemischen PSMA-RLT.

E.2.2

Secondary objectives of the trial

Secondary objective:
• Estimate duration of PSA response and imaging response to [177Lu]Lu-PSMAI&T-RLT as well as their stability.
• Analyze androgen-deprivation therapy (ADT)- and treatment-free survival
• Determine patient’s quality of life under the systemic [177Lu]Lu-PSMAI&T-RLT using the questionnaires: European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ) and Functional Assessment of Cancer Therapy–Prostate total score (FACT-P).

Sekundäre Ziele:
- Abschätzung der Dauer des PSA-Ansprechens und des Ansprechens auf die Bildgebung auf [177Lu]Lu-PSMAI&T-RLT sowie deren Stabilität.
- Analyse des Überlebens nach Androgenentzugstherapie (ADT) und des behandlungsfreien Überlebens
- Ermittlung der Lebensqualität der Patienten unter der systemischen [177Lu]Lu-PSMAI&T-RLT anhand von Fragebögen: European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ) und Functional Assessment of Cancer Therapy-Prostate total score (FACT-P).

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

• Patients must be adults between 18 and 80 years of age.
• Patients with BCR after RP and RT with a PSA doubling-time (DT) of ≤ 12 months.
• No hormonal therapy within the last 12 months or recovered testosterone levels.
• PSMA PET negative result for local recurrence; presence of distant metastases is allowed: (cN0, cM0/cM1).
• Eastern Cooperative Oncology Group (ECOG) Performance Status: 0-1
• Patients must have adequate bone marrow reserve: WBC ≥1.5 x 109 /L, Platelets ≥100 x 109 /L and Haemoglobin ≥9 g/dL.
• Patients must have adequate renal function with eGFR ≥ 50mL/min/1.73m2 using the Modification of Diet Renal Disease (MDRD) equation and an Albumin level of ≥2.5 g/dL.
• Patients must be able to sign Informed Consent Form.

- Die Patienten müssen Erwachsene ≥ 18 Jahre alt sein.
- Patienten mit BCR nach RP und RT mit einer PSA-Verdopplungszeit (PSADT) von ≤
12Monaten.
- Keine Hormontherapie innerhalb der letzten 12 Monate und/oder wiederhergestellte
Testosteronwerte.
- [68Ga]Ga-PSMA-11-PET mit negativem Ergebnis bei lokalem Wiederauftreten; das
Vorhandensein von Fernmetastasen ist zulässig: (cN0, cM0/cM1).
- Eastern Cooperative Oncology Group (ECOG) Leistungsstatus: 0-1
- Die Patienten müssen über eine ausreichende Knochenmarkreserve verfügen: WBC ≥1,5 x
109 /L, Thrombozyten ≥100 x 109 /L und Hämoglobin ≥9 g/dL.
- Die Patienten müssen eine ausreichende Nierenfunktion mit einer eGFR ≥ 50mL/
min/1,73m2 unter Verwendung der Modification of Diet Renal Disease (MDRD)-Gleichung
und einem Albuminspiegel von ≥2,5 g/dL haben.
- Die Patienten müssen in der Lage sein, eine Einverständniserklärung zu unterzeichnen.

E.4

Principal exclusion criteria

- Concomitant participation in any other interventional trial.
- Concurrent severe oncologic and medical conditions that result in patients not having a life expectancy of longer than one year.
- Presence of clinically relevant somatic or psychiatric diseases that might interfere with the objectives and assessments of the study.
- Complete urinary out-flow obstruction or severe unmanageable urinary incontinence.

- Gleichzeitige Teilnahme an einer anderen interventionellen Studie.
- Gleichzeitige schwere onkologische und medizinische Erkrankungen, die dazu führen,
dass die Patienten keine Lebenserwartung von mehr als einem Jahr haben.
- Vorhandensein klinisch relevanter somatischer oder psychiatrischer Erkrankungen, die
die Ziele und Bewertungen der Studie beeinträchtigen könnten.
- Vollständige Obstruktion des Harnabflusses oder schwere, nicht beherrschbare
Harninkontinenz.

E.5 End points

E.5.1

Primary end point(s)

- Response to the PSMA-RLT in terms decline of > 50% of PSA baseline value.
- Toxicity as reflected by pathological decline of values of blood picture, kidney and liver functions from baseline levels assessed by CTCAE (v5.0)

- Ansprechen auf PSMA-RLT im Sinne eines Rückgangs von > 50 % des PSA-Basiswerts.
- Toxizität im Sinne einer pathologischen Verschlechterung von Blutbild, Nieren- und Leberfunktionswerten im Vergleich zum Ausgangswert, bewertet nach CTCAE (v5.0).

E.5.1.1

Timepoint(s) of evaluation of this end point

One and a half years after the start of the study

Eineinhalb Jahre nach Beginn der Studie

E.5.2

Secondary end point(s)

- Time (in weeks) to PSA progression (25% above pre-PSMA-RLT nadir) after completion of therapy
- Imaging-progression free survival, defined as appearance of > 2 new lesions or increase in PSMA uptake or tumor PET volume by 30% or more.
- Duration (in weeks) of treatment-free survival, defined as time from last PSMA-RLT to first PCa-directed therapy.
- Duration (in weeks) of ADT-free survival, defined as time from last PSMA-RLT to first ADT administration. ADT will be administered in a case of progression; either PSA or imaging, as defined above.
- Descriptive analysis of QoL from the questionnaires: FACT-P, EORTC QLQ.
- Assessment of general healthcare costs for every patient during the entire study time.

- Zeit (in Wochen) bis zur PSA-Progression (25% über dem Nadir vor dem PSMA-RLT) nach Abschluss der Therapie.
- Bildgebendes progressionsfreies Überleben, definiert als Auftreten von > 2 neuen Läsionen oder Zunahme der PSMA-Aufnahme oder des Tumor-PET-Volumens um 30% oder mehr.
- Dauer (in Wochen) des behandlungsfreien Überlebens, definiert als Zeit vom letzten PSMA-RLT bis zur ersten PCa-gesteuerten Therapie.
- Dauer (in Wochen) des ADT-freien Überlebens, definiert als Zeit vom letzten PSMA-RLT bis zur ersten ADT-Verabreichung. Die ADT wird im Falle einer Progression verabreicht; entweder PSA oder Bildgebung, wie oben definiert.
- Deskriptive Analyse der Lebensqualität anhand der Fragebögen: FACT-P, EORTC QLQ.
- Bewertung der allgemeinen Gesundheitskosten für jeden Patienten während des gesamten Studienzeitraums.

E.5.2.1

Timepoint(s) of evaluation of this end point

One and a half years after the start of the study

Eineinhalb Jahre nach Beginn der Studie

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

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

Evaluation of therapeutic toxicity of the systemic PSMA-RLT

Bewertung der therapeutischen Toxizität der systemischen PSMA-RLT

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)

Yes

E.7.3

Therapeutic confirmatory (Phase III)

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

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

Yes

E.8.1.7.1

Other trial design description

Prospektive, einarmige, einzentrige Phase-II-Studie.

Prospective single-center one-arm phase II study

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

E.8.2.4

Number of treatment arms in the trial

E.8.3

The trial involves single site in the Member State concerned

Yes

E.8.4

The trial involves multiple sites in the 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

E.8.6.2

Trial being conducted completely outside of the EEA

E.8.7

Trial has a data monitoring committee

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

- Two consecutive PSA rises (at least one week apart) leading to increase >50% from baseline 4 weeks after the last radioligand therapy cycle

- Emergence of severe therapeutic toxicities as assessed by CTCAE (v5.0).

- Zwei aufeinanderfolgende PSA-Anstiege (im Abstand von mindestens einer Woche), die 4 Wochen nach dem letzten Radioliganden-Therapiezyklus zu einem Anstieg von >50 % gegenüber dem Ausgangswert führen

- Auftreten schwerwiegender therapeutischer Toxizitäten, bewertet nach CTCAE (v5.0).

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

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

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

F.4.2

For a multinational trial

F.4.2.2

In the whole clinical trial

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)

None

Keine

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	Medical University of Vienna

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

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2023-07-31

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2023-11-17

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

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