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    Summary
    EudraCT Number:2020-003968-56
    Sponsor's Protocol Code Number:CAAA617C12301
    National Competent Authority:Belgium - FPS Health-DGM
    Clinical Trial Type:EEA CTA
    Trial Status:Trial now transitioned
    Date on which this record was first entered in the EudraCT database:2021-04-16
    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
    Expand All   Collapse All
    A. Protocol Information
    A.1Member State ConcernedBelgium - FPS Health-DGM
    A.2EudraCT number2020-003968-56
    A.3Full 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.3.1Title 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.3.2Name or abbreviated title of the trial where available
    PSMAddition
    A.4.1Sponsor's protocol code numberCAAA617C12301
    A.5.4Other Identifiers
    Name:IND No : Number:133925 (68Ga-PSMA-11)
    Name:IND No:Number:133661 (177Lu-PSMA-617)
    A.7Trial is part of a Paediatric Investigation Plan No
    A.8EMA Decision number of Paediatric Investigation Plan
    B. Sponsor Information
    B.Sponsor: 1
    B.1.1Name of SponsorNovartis Pharma AG
    B.1.3.4CountrySwitzerland
    B.3.1 and B.3.2Status of the sponsorCommercial
    B.4 Source(s) of Monetary or Material Support for the clinical trial:
    B.4.1Name of organisation providing supportNovartis Pharma AG
    B.4.2CountrySwitzerland
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationNovartis Pharma AG
    B.5.2Functional name of contact pointClinical Trial Information Desk
    B.5.3 Address:
    B.5.3.1Street AddressForum 1, Novartis Campus
    B.5.3.2Town/ cityBasel
    B.5.3.3Post code4056
    B.5.3.4CountrySwitzerland
    B.5.4Telephone number+41 61 324 1111
    B.5.5Fax number+41 61 324 8001
    B.5.6E-mailclinicaltrial.enquiries@novartis.com
    D. IMP Identification
    D.IMP: 1
    D.1.2 and D.1.3IMP RoleTest
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation Yes
    D.2.1.1.1Trade name Locametz
    D.2.1.1.2Name of the Marketing Authorisation holderNovartis Europharm Limited
    D.2.1.2Country which granted the Marketing AuthorisationEuropean Union
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
    D.2.5.1Orphan drug designation number
    D.3 Description of the IMP
    D.3.1Product namePSMA-11 25 µg, Kit for radiopharmaceutical preparation
    D.3.2Product code AAA517
    D.3.4Pharmaceutical form Kit for radiopharmaceutical preparation
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPIntravenous use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNgallium (68Ga) gozetotide
    D.3.9.2Current sponsor codeAAA517
    D.3.9.3Other descriptive nameAAA517
    D.3.9.4EV Substance CodeSUB219371
    D.3.10 Strength
    D.3.10.1Concentration unit µg microgram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number25
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin Yes
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) No
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) No
    D.3.11.3.1Somatic cell therapy medicinal product No
    D.3.11.3.2Gene therapy medical product No
    D.3.11.3.3Tissue Engineered Product No
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    D.3.11.5Radiopharmaceutical medicinal product Yes
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product No
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product No
    D.IMP: 2
    D.1.2 and D.1.3IMP RoleTest
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation Yes
    D.2.1.1.1Trade name Pluvicto
    D.2.1.1.2Name of the Marketing Authorisation holderNovartis Europharm Limited
    D.2.1.2Country which granted the Marketing AuthorisationEuropean Union
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
    D.2.5.1Orphan drug designation number
    D.3 Description of the IMP
    D.3.2Product code AAA617
    D.3.4Pharmaceutical form Solution for injection/infusion
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPIntravenous use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNlutetium(177Lu) vipivotide tetraxetan
    D.3.9.2Current sponsor codeAAA617
    D.3.9.3Other descriptive name177LU-PSMA-617
    D.3.9.4EV Substance CodeSUB192220
    D.3.10 Strength
    D.3.10.1Concentration unit MBq/ml megabecquerel(s)/millilitre
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number1000
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin Yes
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) No
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) No
    D.3.11.3.1Somatic cell therapy medicinal product No
    D.3.11.3.2Gene therapy medical product No
    D.3.11.3.3Tissue Engineered Product No
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    D.3.11.5Radiopharmaceutical medicinal product Yes
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product No
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another 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.1.1Medical condition(s) being investigated
    PSMA-positive metastatic hormone-sensitive prostate cancer (mHSPC)
    E.1.1.1Medical condition in easily understood language
    Prostate cancer
    E.1.1.2Therapeutic area Diseases [C] - Cancer [C04]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 21.1
    E.1.2Level PT
    E.1.2Classification code 10036909
    E.1.2Term Prostate cancer metastatic
    E.1.2System Organ Class 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    E.1.3Condition being studied is a rare disease No
    E.2 Objective of the trial
    E.2.1Main 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.2.2Secondary 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 12, 24 and 48 weeks
    -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 12, 24 and 48 months
    -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.2.3Trial contains a sub-study No
    E.3Principal inclusion 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 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. 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. 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.4Principal 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.5.1Primary 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.5.1.1Timepoint(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.5.2Secondary end point(s)
    Overall survival (OS) is designated as key secondary end point. OS is defined as the time from the date of randomization to the date of death due to any cause

    Secondary end points are the following:
    - PSA90 response is defined as the proportion of patients who have a ≥90% decrease in PSA from baseline that is confirmed by a second (the next) PSA measurement ≥4 weeks later.

    - PSA90

    - Time to development of mCRPC is defined as the time from date of randomization to disease progression despite androgen deprivation therapy (ADT) presenting as either a continuous rise in serum prostate-specific antigen (PSA) levels, the progression of pre-existing disease, and/or the appearance of new metastases.

    - PFS is defined as the time from date of randomization to the date of first documented progression by investigator assessment (radiographic progression, clinical progression, PSA progression) or death from any cause, whichever occurs first

    - PFS2 is defined as time from date of randomization to the first documented progression by investigator assessment (radiographic progression, clinical progression, PSA progression) on next-line therapy or death from any cause, whichever occurs first.

    - Proportion of patients with PSA < 0.2 ng/mL

    - ORR, DCR, TTR, DOR, TTSTP

    - Safety: incidence and severity of AEs and serious adverse event (SAE)s, changes in laboratory values, vital signs and ECGs. Any clinically significant lab, vital signs, ECG abnormalities will be captured as an AE.

    - Tolerability: dose interruptions, reductions and dose intensity

    - HRQoL as assessed by Functional Assessment of Cancer Therapy Prostate (FACT-P), Brief Pain Inventory (Short Form (BPI-SF) and European

    - Quality of Life (EuroQol) 5 Domain 5 Level scale (EQ-5D-5L)

    - Time to SSE (TTSSE) defined as date of randomization to the date of first new symptomatic pathological bone fracture, spinal cord compression, tumor-related orthopedic surgical intervention, requirement for radiation therapy to relieve bone pain or death from any cause, whichever occurs first
    E.5.2.1Timepoint(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 12, 24 and 48 weeks.

    Continuously during study for other secondary endpoints.
    E.6 and E.7 Scope of the trial
    E.6Scope of the trial
    E.6.1Diagnosis No
    E.6.2Prophylaxis No
    E.6.3Therapy Yes
    E.6.4Safety Yes
    E.6.5Efficacy Yes
    E.6.6Pharmacokinetic No
    E.6.7Pharmacodynamic Yes
    E.6.8Bioequivalence No
    E.6.9Dose response No
    E.6.10Pharmacogenetic No
    E.6.11Pharmacogenomic No
    E.6.12Pharmacoeconomic No
    E.6.13Others No
    E.7Trial type and phase
    E.7.1Human pharmacology (Phase I) No
    E.7.1.1First administration to humans No
    E.7.1.2Bioequivalence study No
    E.7.1.3Other No
    E.7.1.3.1Other trial type description
    E.7.2Therapeutic exploratory (Phase II) No
    E.7.3Therapeutic confirmatory (Phase III) Yes
    E.7.4Therapeutic use (Phase IV) No
    E.8 Design of the trial
    E.8.1Controlled Yes
    E.8.1.1Randomised Yes
    E.8.1.2Open Yes
    E.8.1.3Single blind No
    E.8.1.4Double blind No
    E.8.1.5Parallel group No
    E.8.1.6Cross over Yes
    E.8.1.7Other No
    E.8.2 Comparator of controlled trial
    E.8.2.1Other medicinal product(s) Yes
    E.8.2.2Placebo No
    E.8.2.3Other Yes
    E.8.2.3.1Comparator description
    Standard of care
    E.8.2.4Number of treatment arms in the trial2
    E.8.3 The trial involves single site in the Member State concerned No
    E.8.4 The trial involves multiple sites in the Member State concerned Yes
    E.8.4.1Number of sites anticipated in Member State concerned5
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA47
    E.8.6 Trial involving sites outside the EEA
    E.8.6.1Trial being conducted both within and outside the EEA Yes
    E.8.6.2Trial being conducted completely outside of the EEA No
    E.8.6.3If 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.8.7Trial 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.8.9.1In the Member State concerned years3
    E.8.9.1In the Member State concerned months6
    E.8.9.1In the Member State concerned days11
    E.8.9.2In all countries concerned by the trial years4
    E.8.9.2In all countries concerned by the trial months9
    E.8.9.2In all countries concerned by the trial days0
    F. Population of Trial Subjects
    F.1 Age Range
    F.1.1Trial has subjects under 18 No
    F.1.1.1In Utero No
    F.1.1.2Preterm newborn infants (up to gestational age < 37 weeks) No
    F.1.1.3Newborns (0-27 days) No
    F.1.1.4Infants and toddlers (28 days-23 months) No
    F.1.1.5Children (2-11years) No
    F.1.1.6Adolescents (12-17 years) No
    F.1.2Adults (18-64 years) Yes
    F.1.2.1Number of subjects for this age range: 338
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 788
    F.2 Gender
    F.2.1Female No
    F.2.2Male Yes
    F.3 Group of trial subjects
    F.3.1Healthy volunteers No
    F.3.2Patients Yes
    F.3.3Specific vulnerable populations No
    F.3.3.1Women of childbearing potential not using contraception No
    F.3.3.2Women of child-bearing potential using contraception No
    F.3.3.3Pregnant women No
    F.3.3.4Nursing women No
    F.3.3.5Emergency situation No
    F.3.3.6Subjects incapable of giving consent personally No
    F.3.3.7Others Information not present in EudraCT
    F.4 Planned number of subjects to be included
    F.4.1In the member state44
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 329
    F.4.2.2In 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
    N.Competent Authority Decision Authorised
    N.Date of Competent Authority Decision2021-05-07
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2021-07-29
    P. End of Trial
    P.End of Trial StatusTrial now transitioned
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