Clinical Trials Register

Summary
EudraCT Number:	2020-003968-56
Sponsor's Protocol Code Number:	CAAA617C12301
National Competent Authority:	Denmark - DHMA
Clinical Trial Type:	EEA CTA
Trial Status:	Trial now transitioned
Date on which this record was first entered in the EudraCT database:	2021-03-17
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

Denmark - DHMA

A.2

EudraCT number

2020-003968-56

A.3

Full title of the trial

PSMAddition : An International Prospective Open-label, Randomized, Phase III Study comparing 177Lu-PSMA-617 in combination with Standard of Care, versus Standard of Care alone, in adult male patients with Metastatic Hormone Sensitive Prostate Cancer (mHSPC)

A.3.1

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

An Open-label study comparing 177LuPSMA-617 plus Standard of Care vs. Standard of Care in the Treatment of mHSPC

A.3.2

Name or abbreviated title of the trial where available

PSMAddition

A.4.1

Sponsor's protocol code number

CAAA617C12301

A.5.4

Other Identifiers

Name:	IND No :	Number:	133925 (68Ga-PSMA-11)
Name:	IND No:	Number:	133661 (177Lu-PSMA-617)

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	Novartis Pharma AG
B.1.3.4	Country	Switzerland
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	Novartis Pharma AG
B.4.2	Country	Switzerland
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Novartis Healthcare AS
B.5.2	Functional name of contact point	Medical Information
B.5.3	Address:
B.5.3.1	Street Address	Edvard Thomsens Vej 14
B.5.3.2	Town/ city	Kopenhagen S
B.5.3.3	Post code	2300
B.5.3.4	Country	Denmark
B.5.6	E-mail	skriv.til@novartis.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	Locametz
D.2.1.1.2	Name of the Marketing Authorisation holder	Novartis Europharm Limited
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	PSMA-11 25 µg, Kit for radiopharmaceutical preparation
D.3.2	Product code	AAA517
D.3.4	Pharmaceutical form	Kit for radiopharmaceutical preparation
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	gallium (68Ga) gozetotide
D.3.9.2	Current sponsor code	AAA517
D.3.9.3	Other descriptive name	AAA517
D.3.9.4	EV Substance Code	SUB219371
D.3.10	Strength
D.3.10.1	Concentration unit	µg microgram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	25
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.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	Pluvicto
D.2.1.1.2	Name of the Marketing Authorisation holder	Novartis Europharm Limited
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.3.2	Product code	AAA617
D.3.4	Pharmaceutical form	Solution for injection/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	lutetium(177Lu) vipivotide tetraxetan
D.3.9.2	Current sponsor code	AAA617
D.3.9.3	Other descriptive name	177LU-PSMA-617
D.3.9.4	EV Substance Code	SUB192220
D.3.10	Strength
D.3.10.1	Concentration unit	MBq/ml megabecquerel(s)/millilitre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	1000
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

PSMA-positive metastatic hormone-sensitive prostate cancer (mHSPC)

E.1.1.1

Medical condition in easily understood language

Prostate 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	10036909
E.1.2	Term	Prostate cancer metastatic
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 main objective of the trial is to evaluate radiographic progression free survival (rPFS) as assessed by Blinded Independent Review Committee (BIRC) in patients with mHSPC receiving Standard of Care and 177Lu-PSMA-617 versus patients receiving Standard of Care without 177Lu-PSMA-617.

E.2.2

Secondary objectives of the trial

Key Secondary objective is to evaluate the contribution of 177Lu-PSMA-617 to Standard of Care in terms of overall survival (OS) in patients with mHSPC.

Secondary objectives are :
- To evaluate PSA90 response at 3, 6 and 12 months
-To evaluate the time to development of metastatic castration resistant prostate cancer (mCRPC) as determined by investigators.
- To evaluate Progression Free Survival (PFS)
- To evaluate the second progression Free Survival (PFS2)
- To evaluate the change in the nadir levels of PSA < 0.2 ng/mL at months 3, 6 and 12
- To evaluate the overall response rate (ORR), disease control rate (DCR), time to response (TTR), duration of response (DOR) and Time to soft tissue progression (TTSTP)
- To evaluate safety and tolerability of 177LuPSMA-617
- To assess the effect of 177Lu-PSMA-617 on the health-related quality of life (HRQoL)
- To evaluate the time from the date of randomization to the date to first symptomatic skeletal event (SSE).

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

English 1. Signed informed consent must be obtained prior to participation in the
study
2. Patients must be adults ≥18 years of age
3. Patients must have an ECOG performance status of 0 to 2
4. Patients must have a life expectancy >9 months as determined by the
study investigator
5. Patients must have metastatic prostate cancer with histologically or
cytologically confirmed adenocarcinoma (current or prior biopsy of the
prostate and/or metastatic site)
6. Patients must have evidence of PSMA-positive disease as seen on a
68Ga-PSMA-11 PET/CT scan, and eligible as determined by the sponsor's
central reader
7. Patients must have at least one metastatic bone and/or soft
tissue/visceral lesion documented in the following manners within 28
days prior randomization:
a. Metastatic disease to the bone (in any distribution) visible on 99Tc-
MDP bone scintigraphy on either pre-ADT scans or baseline scans AND/
OR
b. Lymph node metastases of any size or distribution. If lymph nodes are
the only site of metastasis, then at least one must be at least 1.5 cm in
short axis AND outside of the pelvis AND/ OR
c. Visceral metastases of any size or distribution. If a participant has a
history of visceral metastases at any time prior to randomization, he
should be coded as having visceral metastases at baseline (i.e., patients
with visceral metastases prior to ADT that disappear at baseline will be
counted as having visceral metastases and would therefore have high
volume disease for stratification purposes).
8. Patients must have adequate organ function:
• Bone marrow reserve
ANC ≥1.5 x 109/L
Platelets ≥100 x 109/L
Hemoglobin ≥9 g/dL
• Hepatic
• Total bilirubin ≤2 x the institutional upper limit of normal (ULN), for
patients with known Gilbert's Syndrome ≤3 x ULN is permitted. Alanine
aminotransferase (ALT) or aspartate aminotransferase (AST) ≤3.0 x ULN
OR ≤5.0 x ULN for patients with liver metastases
• Renal
• eGFR ≥ 50 mL/min/1.73m2 using the Modification of Diet in Renal
Disease (MDRD) equation
9. Albumin ≥2.5 g/dL
10. Human immunodeficiency virus (HIV)-infected patients who are
healthy and have a low risk of acquired immune deficiency syndrome
(AIDS)-related outcomes can participate in this trial
other protocol-defined inclusion criteria may apply

E.4

Principal exclusion criteria

1. Patients with rapidly progressing tumor that requires urgent exposure
to taxane-based chemotherapy
2. Any prior systemic anti-prostate cancer therapy (with the exception of
the drugs listed on inclusion criteria 11), including chemotherapy, Poly
(adenosine diphosphate-ribose) polymerase (PARP) inhibitors,
immunotherapy or biological therapy (including monoclonal antibodies).
3. Concurrent cytotoxicity chemotherapy, immunotherapy, radioligand
therapy, PARP inhibitor, biological therapy or investigational therapy
4. Previous treatment with any of the following within 6 months of
randomization: Strontium-89, Samarium-153, Rhenium-186, Rhenium-
188, Radium-223, hemi-body irradiation. Previous PSMA-targeted
radioligand therapy is not allowed
5. Ongoing participation in any other clinical trial
6. Use of other investigational drugs within 30 days prior to day of
randomization
7. Known hypersensitivity to any of the study treatments or its
excipients or to drugs of similar chemical classes
8. Transfusion for the sole purpose of making a participant eligible for
study inclusion
9. Participant with CNS metastases that are neurologically unstable,
symptomatic, or receiving corticosteroids for the purpose of maintaining
neurologic integrity. Participant with epidural disease, canal disease and
prior cord involvement are allowed if those areas have been treated, are
stable, and not neurologically impaired. Patients with parenchymal CNS
metastasis (or a history of CNS metastasis), that have received prior
therapy and are neurologically stable, asymptomatic and not receiving
steroids for CNS metastases, are allowed; baseline and subsequent
radiological imaging for them must include evaluation of the brain
(magnetic resonance imaging (MRI) preferred or CT with contrast).
10. Diagnosed with other malignancies that are expected to alter life
expectancy or may interfere with disease assessment. However,
participants with a prior history of malignancy that has been adequately
treated and who have been disease free, treatment free for more than 3
years prior to randomization, or participants with adequately treated
non-melanoma skin cancer, superficial bladder cancer are eligible.
other protocol-defined exclusion criteria may apply

E.5 End points

E.5.1

Primary end point(s)

Radiographic progression-free survival (rPFS) is designated as primary endpoint. rPFS is defined as the time from the date of randomization to the date of first documented radiographic disease progression as assessed by blinded independent central review (BIRC) and as outlined in Prostate Cancer Working Group 3 (PCWG3) Guidelines (Scher et al 2016) or death due to any cause

E.5.1.1

Timepoint(s) of evaluation of this end point

Radiographic progression-free survival (rPFS) will be evaluated every 12 weeks (+/-7 days) after first dose of 177Lu-PSMA-617 (investigational arm) or first dose of ARDT (Control arm) - independant of dose delays during 24 months, then every 16 weeks (+/-7days) until radiographic disease progression, death, withdraw of consent, loss to FUP, subject/guardian decision.

E.5.2

Secondary end point(s)

For OS: continuously during study treatment and post-treatment
followup
ORR, DCR, TTR, DOR, TTSTP will be evaluated based on PCWG3 modified
RECIST 1.1
PSA90 and proportion of patients with PSA < 0.2 ng/mL will be
evaluated at 12, 24 and 48 weeks.
Continuously during study for other secondary endpoints.

E.5.2.1

Timepoint(s) of evaluation of this end point

For OS: continuously during study treatment and post-treatment follow-up

ORR, DCR, TTR, DOR, TTSTP will be evaluated based on PCWG3 modified RECIST 1.1

PSA90 and proportion of patients with PSA < 0.2 ng/mL will be evaluated at 3, 6 and 12 months.

Continuously during study for other secondary endpoints.

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

Yes

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

E.8.1.6

Cross over

Yes

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

Standard of care

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

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

Singapore

Switzerland

Taiwan

Austria

Belgium

Canada

China

Czechia

Denmark

France

Germany

Italy

Japan

Korea, Republic of

Netherlands

Poland

Russian Federation

Spain

Sweden

United Kingdom

United States

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

Last visit of the last participant (LVLP)

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:

338

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

788

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

Information not present in EudraCT

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

329

F.4.2.2

In the whole clinical trial

1126

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

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

2021-04-15

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2021-11-04

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

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