Prostate Cancer Clinical Trial
An International Prospective Open-label, Randomized, Phase III Study Comparing 177Lu-PSMA-617 in Combination With SoC, Versus SoC Alone, in Adult Male Patients With mHSPC
Summary
The purpose of this study is to evaluate the efficacy and safety of 177Lu-PSMA-617 in combination with Standard of Care, versus Standard of Care alone, in adult male patients with mHSPC. In this study, the SoC is defined as a combination of Androgen Receptor Directed Therapy + Androgen Deprivation Therapy. Approximately 1126 patients will be randomized in this study.
Full Description
In this international, open-label, prospective, phase III study, where approximately 1126 patients with treatment naïve or minimally treated PSMA-positive mHSPC will be randomized in a 1:1 ratio to receive Standard of Care (SoC) with or without the radioligand 177Lu-PSMA-617.
The primary objective of the study is to determine whether the combination of 177Lu-PSMA-617 + SoC improves rPFS over that obtained by administration of SoC alone in mHSPC patients.
The randomization will be stratified according to the following three factors: disease volume (high v low), age >= 70 years (yes/no), and on Previous or planned treatment (prostatectomy or radiation) to primary (prostate) tumor (yes/no).
Study duration: approximately 50 months. screening period: after signing ICF, patients will be assessed for eligibility and will be scanned with 68Ga PSMA-11 to identify PSMA expression status. Following completion of all required screening procedures and verifying participant eligibility, the participant will be randomized via the interactive response technology (IRT) system.
Amended protocol includes an option for participants to be enrolled into a separate long-term safety follow-up study, and China extension cohort (40 to 60 participants)
Prior treatment:
Up to 45 days of LHRH agonist/antagonists is allowed prior to ICF signature. If patient did not start the ADT prior randomization, ADT should start as soon as possible and ideally no later than 2 weeks after randomization.
Up to 45 days of ARDT is allowed prior ICF signature. If patient did not start the ARDT prior randomization, ARDT should start as soon as possible and ideally no later than 2 weeks after randomization. Patients will received ARDT as per label instructions.
Randomization period:
The participant will be randomized in a 1:1 ratio to receive Standard of Care (SoC) with or without the radioligand 177Lu-PSMA-617.
Treatment period:
Patients randomized to the investigational arm (i.e. SoC+177Lu-PSMA-617): Patients will receive SoC as per label instructions, after randomization, if not started earlier and in the time frame allowed by the protocol. Patients must begin 177Lu-PSMA-617 dosing within 14 days after randomization or as soon as possible after the product is received. 177Lu-PSMA-617 is administered at the dose of 7.4 GBq (+/- 10%), once every 6 weeks (+/- 1 week) for a planned 6 cycles.
Patients randomized to the control arm will begin receiving SoC as per label instructions after randomization, if not started earlier and in the time frame allowed by the protocol.
The primary endpoint of rPFS will be assessed by a centralized blinded image review committee (i.e., BIRC) using radiographic images provided by the treating physician.
An end of treatment (EOT) visit will be performed when participants permanently discontinue study treatment.
Cross-over period:
After patients randomized to the SoC alone (i.e., control) arm experience radiographic progression (the rPFS event) as confirmed by BIRC, they will be allowed to cross-over to receive 177Lu-PSMA-617 +/- SoC per the discretion of the treating physician. If cross-over to 177Lu-PSMA-617 is selected, then 177Lu-PSMA-617 will be administered with the same dose/schedule as participants who were initially randomized to receive 177Lu-PSMA-617 as described above. Study cross-over participants for whom 177Lu-PSMA-617 is discontinued must have a second End of Treatment (EOT2) visit performed =< 7 days and enter the Post-treatment Follow-up .
Post-Treatment Follow-Up (Safety, Efficacy):
After treatment discontinuation, all participants will be followed for safety with a 30-day safety follow-up visit (FUP) as well as longer term safety follow-up assessments for a period of approximately 12 months.
Participants who discontinue study treatment without having progressive disease confirmed by BIRC, will continue to be assessed for efficacy (efficacy follow-up) during the post-treatment follow-up period until the occurrence of their BIRC-confirmed radiographic disease progression (rPFS) event , or if the total number of protocol-defined rPFS events has occurred triggering the primary analysis, whichever occurs first.
Survival Follow-Up:
After study treatment discontinuation, or post-treatment follow-up period discontinuation, the participant's status will be collected every 90 days (via phone calls) as part of the survival follow-up. Every effort should be made to comply with the survival follow-up schedule and ensure collection of participant survival. The survival follow-up and the study will end when the number of OS events required for final OS analysis will be reached.
Eligibility Criteria
Inclusion Criteria:
Participants eligible for inclusion in this study must meet all of the following criteria:
Signed informed consent must be obtained prior to participation in the study
Patients must be adults ≥18 years of age
Patients must have an ECOG performance status of 0 to 2
Patients must have a life expectancy >9 months as determined by the study investigator
Patients must have metastatic prostate cancer with histologically or cytologically confirmed adenocarcinoma (current or prior biopsy of the prostate and/or metastatic site)
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
Patients must have at least one documented metastatic bone and/or soft tissue/visceral lesion documented in the following manners within 28 days prior randomization:
Metastatic disease to the bone (in any distribution) visible on 99Tc-MDP bone scintigraphy on either pre-ADT scans or baseline scans AND/OR
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
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).
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
Albumin ≥2.5 g/dL
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
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 study therapy or after 45 days whatever happens first.
If received, prior LHRH agonist/antagonist with or without first generation anti-androgen 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 CYP17 inhibitor or ARDT 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.
Participants with rapidly progressing tumor that requires urgent exposure to taxane-based chemotherapy
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).
Concurrent cytotoxicity chemotherapy, immunotherapy, radioligand therapy, PARP inhibitor, biological therapy or investigational therapy
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
Ongoing participation in any other clinical trial
Use of other investigational drugs within 30 days prior to day of randomization
Known hypersensitivity to any of the study treatments or its excipients or to drugs of similar chemical classes
Transfusion for the sole purpose of making a participant eligible for study inclusion
Participants with CNS metastases that are neurologically unstable, symptomatic, or receiving corticosteroids for the purpose of maintaining neurologic integrity. Participants with epidural disease, canal disease and prior cord involvement are allowed if those areas have been treated, are stable, and not neurologically impaired. Participants 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 must include evaluation of the brain (magnetic resonance imaging (MRI) preferred or CT with contrast).
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.
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).
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% with improvement in symptoms to class < 3.
History or current diagnosis of ECG abnormalities indicating significant risk of safety for participants in the study such as: Concomitant clinically significant cardiac arrhythmias, e.g. sustained ventricular tachycardia, complete left bundle branch block, high-grade atrioventricular (AV) block (e.g., bifascicular block, Mobitz type II and third degree AV block)
History of familial long QT syndrome or known family history of Torsades de Pointes
Cardiac or cardiac repolarization abnormality, including any of the following: History of myocardial infarction (MI), angina pectoris, or coronary artery bypass graft (CABG) within 6 months prior to ICF signature
History of somatic or psychiatric disease/condition that may interfere with the objectives and assessments of the study
Symptomatic cord compression, or clinical or radiologic findings indicative of impending cord compression
Any condition that precludes raised arms position
Unmanageable concurrent bladder outflow obstruction or urinary incontinence. Note: participants with bladder outflow obstruction or urinary incontinence, which is manageable and controlled with best available standard of care (incl. pads, drainage) are allowed.
Sexually active males unwilling to use a condom during intercourse while taking study treatment and for 14 weeks after stopping study treatment. A condom is required for all sexually active male participants to prevent them from fathering a child AND to prevent delivery of study treatment via seminal fluid to their partner. In addition, male participants must not donate sperm for the time period specified above. If local regulations deviate from the contraception methods listed above to prevent pregnancy, local regulations apply and will be described in the ICF
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There are 163 Locations for this study
Scottsdale Arizona, 85259, United States More Info
Principal Investigator
Los Angeles California, 90073, United States More Info
Principal Investigator
Los Angeles California, 90095, United States More Info
Principal Investigator
Orange California, 92686, United States More Info
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Orange California, 92868, United States More Info
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Palo Alto California, 94304, United States More Info
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Santa Barbara California, 93105, United States More Info
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Santa Monica California, 90404, United States More Info
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Stanford California, 94305, United States More Info
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Aurora Colorado, 80045, United States More Info
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Longmont Colorado, 80501, United States More Info
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Hartford Connecticut, 06102, United States More Info
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Washington District of Columbia, 20007, United States More Info
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Washington District of Columbia, 20422, United States More Info
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Jacksonville Florida, 32224, United States More Info
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Jacksonville Florida, 32256, United States More Info
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Miami Florida, 33136, United States More Info
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Miami Florida, 33173, United States More Info
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Panama City Florida, 32405, United States More Info
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Athens Georgia, 30607, United States More Info
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Chicago Illinois, 60611, United States More Info
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Chicago Illinois, 60612, United States More Info
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Chicago Illinois, 60637, United States More Info
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Hines Illinois, 60141, United States More Info
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Skokie Illinois, 60077, United States More Info
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Fort Wayne Indiana, 46845, United States More Info
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Indianapolis Indiana, 46202, United States More Info
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New Orleans Louisiana, 70112, United States More Info
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New Orleans Louisiana, 70121, United States More Info
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Baltimore Maryland, 21231, United States More Info
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Boston Massachusetts, 02115, United States More Info
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Boston Massachusetts, 02215, United States More Info
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Ann Arbor Michigan, 48105, United States More Info
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Ann Arbor Michigan, 48109, United States More Info
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Royal Oak Michigan, 48073, United States More Info
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Minneapolis Minnesota, 55455, United States More Info
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Rochester Minnesota, 55905, United States More Info
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Jackson Mississippi, 39216, United States More Info
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Saint Louis Missouri, 63104, United States More Info
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Saint Louis Missouri, 63106, United States More Info
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Saint Louis Missouri, 63110, United States More Info
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Omaha Nebraska, 68130, United States More Info
Principal Investigator
Omaha Nebraska, 68130, United States More Info
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Albuquerque New Mexico, 87131, United States More Info
Principal Investigator
Bronx New York, 10467, United States More Info
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New York New York, 10021, United States More Info
Principal Investigator
New York New York, 10065, United States More Info
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Rochester New York, 14642, United States More Info
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Chapel Hill North Carolina, 27599, United States More Info
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Charlotte North Carolina, 28203, United States More Info
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Durham North Carolina, 27710, United States More Info
Principal Investigator
Cleveland Ohio, 44195, United States More Info
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Columbus Ohio, 43221, United States More Info
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Portland Oregon, 97239, United States More Info
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Hershey Pennsylvania, 17033, United States More Info
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Philadelphia Pennsylvania, 19107, United States More Info
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Pittsburgh Pennsylvania, 15232, United States More Info
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Charleston South Carolina, 29425, United States More Info
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Myrtle Beach South Carolina, 29572, United States More Info
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Dallas Texas, 75216, United States More Info
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Dallas Texas, 75246, United States More Info
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Dallas Texas, 75390, United States More Info
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Houston Texas, 77030, United States More Info
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San Antonio Texas, 78229, United States More Info
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Salt Lake City Utah, 84106, United States More Info
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Charlottesville Virginia, 22908, United States More Info
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Norfolk Virginia, 23502, United States More Info
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Roanoke Virginia, 24014, United States More Info
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Seattle Washington, 98122, United States More Info
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Milwaukee Wisconsin, 53226, United States More Info
Principal Investigator
Innsbruck Tyrol, 6020, Austria
Linz , A-401, Austria
Wien , 1090, Austria
Bruxelles , 1200, Belgium
Gent , 9000, Belgium
Liege , 4000, Belgium
Hamilton Ontario, L8V 5, Canada
Toronto Ontario, M4N 3, Canada
Montreal Quebec, H2W 1, Canada
Montreal Quebec, H3T 1, Canada
Montreal Quebec, H4A 3, Canada
Sherbrooke Quebec, J1H 5, Canada
Quebec , G1R 2, Canada
Nanjing Jiangsu, 21000, China
Shanghai , 20008, China
Olomouc CZE, 779 0, Czechia
Praha 5 , 150 0, Czechia
Copenhagen , DK-21, Denmark
Bordeaux Cedex , 33075, France
Clermont-Ferrand , 63011, France
Lyon , 69373, France
Montpellier , 34298, France
Nantes Cedex 1 , 44093, France
Paris , 75015, France
Paris , 75018, France
Strasbourg , 67200, France
Vandoeuvre , 54511, France
Villejuif Cedex , 94800, France
Essen , 45147, Germany
Koeln , 50937, Germany
Muenchen , 80377, Germany
Muenster , 48149, Germany
Rostock , 18057, Germany
Wuerzburg , 97080, Germany
Nagoya Aichi, 466 8, Japan
Fukuoka city Fukuoka, 812-8, Japan
Sapporo city Hokkaido, 060 8, Japan
Kobe-city Hyogo, 650-0, Japan
Yokohama-city Kanagawa, 236-0, Japan
Kumamoto City Kumamoto, 860-8, Japan
Okayama-city Okayama, 700-8, Japan
Suita Osaka, 565 0, Japan
Kitaadachi-gun Saitama, 362-0, Japan
Hamamatsu-city Shizuoka, 431-3, Japan
Bunkyo ku Tokyo, 113-8, Japan
Bunkyo-ku Tokyo, 113-0, Japan
Bunkyo-ku Tokyo, 113-8, Japan
Chuo ku Tokyo, 104 0, Japan
Chiba , 260-8, Japan
Fukuoka , 811-0, Japan
Fukuoka , 812-0, Japan
Kyoto , 606 8, Japan
Yamagata , 990 9, Japan
Seoul Korea, 05505, Korea, Republic of
Seoul , 03080, Korea, Republic of
Seoul , 03722, Korea, Republic of
Nijmegen Netherland, 6525 , Netherlands
Amsterdam , 1105 , Netherlands
Delft , 2625 , Netherlands
Maastricht , 6229 , Netherlands
Utrecht , 3584C, Netherlands
Gliwice Slaskie, 44-10, Poland
Krakow , 31-50, Poland
Warszawa , 02 78, Poland
San Juan , 00921, Puerto Rico More Info
Principal Investigator
Singapore , 11922, Singapore
Singapore , 16961, Singapore
Sabadell Barcelona, 08208, Spain
Barcelona Catalunya, 08035, Spain
Barcelona Catalunya, 08036, Spain
Hospitalet de LLobregat Catalunya, 08907, Spain
Santiago de Compostela Galicia, 15706, Spain
El Palmar Murcia, 30120, Spain
Madrid , 28034, Spain
Madrid , 28040, Spain
Madrid , 28041, Spain
Madrid , 28046, Spain
Madrid , 28222, Spain
Valencia , 46026, Spain
Goteborg , 413 4, Sweden
Lund , 221 8, Sweden
Stockholm , 17176, Sweden
Bern , 3010, Switzerland
Lausanne , 1011, Switzerland
Zuerich , 8091, Switzerland
Taipei , 10002, Taiwan
Taoyuan , 33305, Taiwan
Sutton Surrey, SM2 5, United Kingdom
Middlesbrough Yorkshire, TS4 3, United Kingdom
Belfast , BT9 7, United Kingdom
Cambridge , CB2 2, United Kingdom
Glasgow , G12 0, United Kingdom
London , EC1A , United Kingdom
London , NW1 2, United Kingdom
London , NW3 2, United Kingdom
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