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SNCTP000004759 | NCT04720157 | BASEC2021-00688

Étude prospective internationale de phase III, randomisée, en ouvert, comparant l’association du 177Lu-PSMA-617 et du traitement recommandé par rapport au traitement recommandé seul, chez des patients, hommes adultes, atteints d’un cancer de la prostate métastatique hormonosensible (CPmHS)

Data source: BASEC (Imported from 27.01.2022), WHO (Imported from 18.01.2022)
Changed: 14.01.2022
Disease category: Prostate Cancer

Brief description of trial (Data source: BASEC)

Les participants éligibles à l’étude seront des hommes atteints d’un CPmHS n’ayant jamais reçu de traitement par privation androgénique (TPA) ou de traitement dirigé contre les récepteurs androgéniques (TDRA) ou n’ayant reçu qu’un traitement minimal (jusqu’à 45 jours). Environ 1126 patients atteints d’un CPmHS seront randomisés avec une probabilité égale de 50% de recevoir initialement le 177Lu-PSMA-617 + traitement recommandé ou le traitement recommandé seul. Le traitement recommandé est défini comme un traitement par privation androgénique (TPA) associé à un traitement dirigé contre les récepteurs androgéniques (TDRA) et il est prescrit par l’investigateur. Pour le 177Lu-PSMA-617, ce traitement est administré par voie intraveineuse toutes les 6 semaines pendant 6 cycles (36 semaines au total). Pour les patients qui reçoivent le traitement recommandé seul, si la maladie s’aggrave (progresse), il sera possible d’obtenir le 177Lu-PSMA-617 si le patient est éligible. L’objectif de l’étude est d’évaluer la survie sans progression radiographique (SSPr) telle qu’évaluée par le Comité d’examen indépendant en aveugle (CEIA) chez des patients atteints d’un CPmHS recevant le traitement recommandé et le 177Lu-PSMA-617 par rapport à des patients recevant le traitement recommandé sans le 177Lu-PSMA-617.

Health conditions investigated (Data source: BASEC)

Cancer de la prostate métastatique hormonosensible (CPmHS)

Health conditions (Data source: WHO)

Prostatic Neoplasms

Rare disease (Data source: BASEC)

No

Intervention investigated (e.g. drug, therapy or campaign) (Data source: BASEC)

Le composé d’imagerie 68Ga-PSMA-11 utilisé à des fins d’imagerie pendant la sélection et le médicament à l’étude 177Lu-PSMA-617 sont les composés interventionnels.
Imagerie 68Ga-PSMA-11:
le 68Ga-PSMA-11 sera administré sous forme d’une dose intraveineuse unique d’environ 150 MBq.

Bras de traitement Lu-PSMA-617:
les participants randomisés dans le bras expérimental recevront 7,4 GBq (200 mCi) +/-10% de ¹⁷⁷Lu-PSMA-617 par voie intraveineuse une fois (1 cycle) toutes les 6 semaines pendant 6 cycles.

Interventions (Data source: WHO)

Diagnostic Test: 68Ga-PSMA-11
Drug: 177Lu-PSMA-617
Drug: ADT
Drug: ARDT

Criteria for participation in trial (Data source: BASEC)

- Le patient doit être atteint d’un cancer métastatique de la prostate avec adénocarcinome confirmé histologiquement ou cytologiquement (biopsie actuelle ou antérieure de la prostate et/ou du site métastatique).
- Les patients doivent présenter des signes de maladie PSMA-positive, observés sur une TEP/TDM à 68Ga-PSMA-11, et être éligibles, comme déterminé par le lecteur central du promoteur.
- Les patients ne doivent pas avoir reçu auparavant de traitement, ou seulement un traitement minimal, par privation androgénique ou privation androgénique dirigé contre les récepteurs androgéniques (jusqu’à 45 jours)

Exclusion criteria (Data source: BASEC)

- Patients atteints d’une tumeur à progression rapide nécessitant une exposition urgente à une chimiothérapie à base de taxanes.
- Tout traitement systémique contre le cancer de la prostate (à l’exception de TPA/TDRA jusqu’à 45 jours), y compris la chimiothérapie, les inhibiteurs de PARP, l’immunothérapie ou un traitement biologique (y compris les anticorps monoclonaux).
- Autre chimiothérapie cytotoxique concomitante, immunothérapie, traitement par radioligand ou traitement expérimental

Inclusion/Exclusion Criteria (Data source: WHO)


Inclusion Criteria:

Participants eligible for inclusion in this study must meet all of the following criteria:

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 documented metastatic disease to bone and/or soft tissue/visceral
sites documented in one of the following manners within 28 days prior randomization:

1. Metastatic disease to the bone (in any distribution) visible on 99Tc-MDP bone
scintigraphy on either pre-ADT scans or baseline scans. OR

2. 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. OR

3. Visceral metastases of any size or distribution. If a subject has a history of
visceral metastases at any time prior to registration, 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

11. Patients must be:

Treatment naïve OR minimally treated with:

- Up to 45 days of luteinizing hormone-releasing hormone (LHRH) agonist /antagonists or
bilateral orchiectomy with or without first generation anti-androgen (e.g.
bicalutamide, flutamide) for metastatic prostate cancer is allowed prior to ICF
signature. If given, first generation anti-androgen must be discontinued prior to
start of therapy.

- If received, prior LHRH agonist/antagonist use in the adjuvant/neo-adjuvant setting
must have been discontinued > 12 months prior to ICF signature AND must not have
exceeded 24 months of therapy AND must not have shown disease progression within 12
months of completing adjuvant/neo-adjuvant therapy.

- Up to 45 days of CYP17 inhibitor or ARDT exposure for metastatic prostate cancer is
allowed prior to ICF signature. No exposure for earlier stages of prostate cancer is
allowed.

Exclusion Criteria:

Participants meeting any of the following criteria are not eligible for inclusion in this
study.

1. Patients with rapidly progressing tumor that requires urgent exposure to taxane-based
chemotherapy

2. Any systemic anti-prostate cancer therapy (with the exception of the drugs listed on
inclusion criteria 11), including chemotherapy, PARP inhibitors, immunotherapy or
biological therapy (including monoclonal antibodies).

3. Other concurrent cytotoxicity chemotherapy, immunotherapy, radioligand 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 subject eligible for study inclusion

9. Patients with CNS metastases that are neurologically unstable, symptomatic, or
receiving corticosteroids for the purpose of maintaining neurologic integrity.
Patients with epidural disease, canal disease and prior cord involvement are eligible
if those areas have been treated, are stable, and not neurologically impaired. For
patients with parenchymal CNS metastasis (or a history of CNS metastasis), baseline
and subsequent radiological imaging 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, patients with a prior history of
malignancy that has been adequately treated and who have been disease free for more
than 3 years are eligible, as are patients with adequately treated non-melanoma skin
cancer, superficial bladder cancer. Note: Patients with a history of CNS metastases
that have received prior therapy and are neurologically stable, asymptomatic and not
receiving corticosteroids are allowed.

11. Concurrent serious (as determined by the Principal Investigator) medical conditions,
including, but not limited to, uncontrolled infection, known active hepatitis B or C,
or other significant co-morbid conditions that in the opinion of the investigator
would impair study participation or cooperation. Participants with an active
documented COVID-19 infection (any grade of disease severity) at time of informed
consent may be included only when completely recovered (in accordance with local
guidance) and had no symptoms for at least 28 days before the first dose of study
medication

12. No active clinically significant cardiac disease defined as any of the following:

- NYHA class 3/4 congestive heart failure within 6 months prior to ICF signature
unless treated with improvement and echocardiogram or MUGA demonstrates EF > 45%

Minimum age: 18 Years
Maximum age: N/A
Sex: Male

Further information on the trial in WHO primary registry

https://trialsearch.who.int/Trial2.aspx?TrialID=NCT04720157

Further information on the trial from WHO database (ICTRP)

https://trialsearch.who.int/Trial2.aspx?TrialID=NCT04720157

Further information on trial

Date trial registered

19.01.2021

Incorporation of the first participant

09.06.2021

Recruitment status

Recruiting

Global completion date of trial

30.11.-0001

Academic title (Data source: WHO)

An 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)

Type of trial (Data source: WHO)

Interventional

Design of the trial (Data source: WHO)

Allocation: Randomized. Intervention model: Crossover Assignment. Primary purpose: Treatment. Masking: None (Open Label).

Phase (Data source: WHO)

Phase 3

Primary end point (Data source: WHO)

Radiographic Progression Free Survival (rPFS)

Secundary end point (Data source: WHO)

Brief Pain Inventory-short Form (PBI-SF)
Change in nadir level of PSA lower than 0.2 ng/ml
Disease Control Rate (DCR)
Duration of Response (DOR)
European Quality of Life ( EuroQoL) -5 Domain 5 Level Scale (EQ-5D-5L)
Functional Assessment of Cancer Therapy - Prostate (FACT-P) Questionnaire
Number of participants with Treatment Emergent Adverse Events
Overall Response Rate (ORR)
Overall Survival (OS)
Progression Free Survival (PFS)
Prostate-specific antigen 90 (PSA90) response
second Progression Free Survival (PFS2)
time to development of mCRPC
Time to first symptomatic skeletal event (SSE).
Time to radiographic soft tissue progression (TTSTP)
Time to Response (TTR)

Contact information (Data source: WHO)

Please refer to primary and secondary sponsors

Trial results (Data source: WHO)

Results summary

no information available yet

Link to the results in the primary register

no information available yet

Information on the availability of individual participant data

no information available yet

Trial sites

Trial sites in Switzerland (Data source: BASEC)

Bern, Lausanne, Zurich

Countries (Data source: WHO)

Switzerland might not appear as site of trial if it has not yet been entered as such in the WHO primary registry.
Austria, Belgium, France, Netherlands, Poland, Spain, Sweden, United States

Contact for further information on the trial

Details of contact in Switzerland (Data source: BASEC)

Myriam Vincent
+41 79 941 82 91
myriam.vincent@novartis.com

Contact for general information (Data source: WHO)

Novartis Pharmaceuticals
Novartis Pharmaceuticals

Contact for scientific information (Data source: WHO)

Novartis Pharmaceuticals
1-888-669-6682
novartis.email@novartis.com

Principal Sponsor/Investigator

Principal sponsor (Data source: WHO)

Novartis Pharmaceuticals

Additional sponsors (Data source: WHO)

Alliance Foundation Trials, LLC.
RTOG Foundation, Inc.

Authorisation by the ethics committee (Data source: BASEC)

Name of the authorising ethics committee (for multicentre studies only the lead committee)

Commission cantonale d’Éthique de la Recherche sur l’être humain Vaud (CER-VD)

Date of authorisation by the ethics committee

10.01.2022

Further trial identification numbers

Trial identification number of the ethics committee (BASEC-ID) (Data source: BASEC)

2021-00688

Secondary ID (Data source: WHO)

2020-003968-56
CAAA617C12301