Study of PSMA-targeted Therapy and Androgen Receptor Suppression in Low-volume Metastatic ProstatE Cancer: SPARKLE Trial (SPARKLE)

A Phase II Randomized Trial of Intermittent Androgen Deprivation Therapy Alone or Combined With [177Lu]Lu-PSMA-617, With or Without Abiraterone and Prednisone, in Patients With Low-Volume Metastatic Hormone-Sensitive Prostate Cancer

This phase II trial tests leuprolide acetate alone versus in combination with 177Lu-PSMA-617, with or without abiraterone acetate and prednisone, for the treatment of hormone-sensitive prostate cancer has spread to a limited number of anatomic sites at the time of initial diagnosis (de novo low volume metastasis) or that has come back after a period of improvement (recurrent). Standard of care treatment for prostate cancer usually includes androgen deprivation therapy, with or without abiraterone acetate and prednisone. Leuprolide acetate is a form of androgen deprivation therapy. It blocks the body from making testosterone (a male hormone) and estradiol (a female hormone). It may stop the growth of prostate cancer cells that need testosterone to grow. 177Lu-PSMA-617 is a type of radioconjugate drug. Upon administration, vipivotide tetraxetan targets and binds to prostate specific membrane antigen (PSMA)-expressing tumor cells. Upon binding, PSMA-expressing tumor cells are destroyed by 177Lu through the specific delivery of radiation. PSMA, a tumor-associated antigen and type II transmembrane protein, is overexpressed on prostate tumor cells. Abiraterone acetate is a type of anti-androgen drug. It blocks tissues from making androgens (male hormones), such as testosterone. This may cause the death of cancer cells that need androgens to grow. Prednisone is in a class of medications called corticosteroids. It is used to reduce inflammation and lower the body's immune response to help lessen the side effects of chemotherapy drugs. Giving 177Lu-PSMA-617 in combination with leuprolide acetate, with or without abiraterone acetate and prednisone, may be more effective at treating patients with recurrent or de novo low volume metastatic hormone-sensitive prostate cancer than giving leuprolide acetate alone.

Study Overview

• Status: Not yet recruiting
• Conditions: Stage IVB Prostate Cancer AJCC v8; De Novo Low Volume Metastatic Castration-Sensitive Prostate Adenocarcinoma; Recurrent Castration-Sensitive Prostate Adenocarcinoma
• Intervention / Treatment: Other: Quality-of-Life Assessment; Procedure: Biospecimen Collection; Drug: Prednisone; Drug: Abiraterone Acetate; Drug: Leuprolide Acetate; Procedure: Single Photon Emission Computed Tomography; Drug: Lutetium Lu 177 Vipivotide Tetraxetan; Procedure: PSMA PET-CT Scan

• Study Type: Interventional
• Enrollment (Estimated): 202
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Clinical Trials Referral Office; Phone Number: 855-776-0015; Email: mayocliniccancerstudies@mayo.edu
• Study Contact Backup: Name: Urology Study Coordinator; Phone Number: 507-422-5076

Study Locations

• United States
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic in Rochester
      • Contact: Clinical Trials Referral Office; Phone Number: 855-776-0015; Email: mayocliniccancerstudies@mayo.edu
      • Contact: Urology Study Coordinator; Phone Number: 507-422-5076
      • Principal Investigator: Matthew K. Tollefson, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Male patients aged 18 years or older
• Signed informed consent must be obtained prior to participation in the study
• Histologically confirmed adenocarcinoma of the prostate
• Prior treatment with radical prostatectomy or radiation therapy for localized disease is required

• Prior treatment with ADT or androgen receptor pathway inhibitor (ARPI) or cytotoxic chemotherapy is permitted if:

  • The last treatment > 12 months from enrollment on the trial
  • The duration of treatment is less than 3 months and no evidence of disease progression on treatment
• Disease detected on PSMA PET/CT scan [PSMA-avid low volume metastasis (LVM)]. Patients with standardized uptake value maximum (SUVMax) lesion/liver >1 [molecular imaging PSMA (miPSMA) score of 2] or lesion/parotid > 1 (miPSMA score of 3) would be included. PET scanners used in the study will comply with current guidelines established by the European Association of Nuclear Medicine (EANM) Research Limited (Ltd) (EARL) for harmonizing PET/CT image acquisition and reconstruction

• Patients with hormone sensitive low volume metastatic disease (LVM); either de novo metastatic or recurrent disease. LVM, as assessed on PSMA PET/CT is defined as:

  • =< 10 total metastatic spots

    • Lymph nodes with short axis of =< 2.5 cm
    • Total tumor volume (TTV) < 200 mL
  • =< 4 bone metastases
  • No brain or liver metastases
• Eastern Cooperative Oncology Group (ECOG) performance 0 - 2
• Hemoglobin >= 9 g/dL
• Platelet count >= 100,000/mm^3
• Absolute neutrophil count >= 1,500/mm^3
• Serum bilirubin =< 1.5 x upper limit of normal (ULN)
• Alanine aminotransferase (ALT)/aspartate aminotransferase (AST) =< 2.5 x ULN
• Serum creatinine =< 1.5 x ULN or an estimated glomerular filtration rate (eGFR) >= 50 mL/min/1.73m^2
• Able to start therapy within 28 days of screening
• Expected life expectancy > 6 months

Exclusion Criteria:

• PSMA-undetectable disease defined as rising prostate specific antigen (PSA) with absence of PSMA-positive lesions in PSMA PET/CT imaging
• PSMA-negative disease defined as lesions detected on imaging that are deemed concerning for active cancer metastasis with PSMA SUVmax less than liver and meeting specific size criteria: lymph nodes with short axis of >= 2.5 cm, visceral lesions with a solid appearance (soft tissue density) >= 1 cm, and bone metastases with a measurable soft tissue component >= 1 cm
• Patient with in-field failure (disease recurrence in prostate bed after primary definitive prostatectomy or radiotherapy)
• Patient with spinal metastatic disease-causing cord compression
• Patient with prior disease progression on ADT [castration resistance prostate cancer (CRPC)]
• Prior treatment with ADT or cytotoxic chemotherapy or ARPI within less than 12 months from enrollment on the trial
• Prior treatment with ADT or ARPI or cytotoxic chemotherapy is permitted only if more than 3 months treatment duration and no evidence of disease progression on treatment
• Patients with severe [Common Terminology Criteria for Adverse Events (CTCAE) grade > 2] xerostomia
• Patients with well documented history of myelosuppression or renal disease that might impair their participation in the trial per medical advice
• 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 non-melanoma skin cancer, superficial bladder cancer are eligible
• Estimated life expectancy < 6 months

• Concurrent serious medical co-morbidities as determined by study investigator and expected to impair participation in the study

  • Subjects with female partners of reproductive potential are required to use effective, medically acceptable methods of birth control (e.g., spermicide in conjunction with a barrier such as a condom or sexual abstinence) while on this study, and for 14 weeks after the last dose of 177Lu-PSMA-617

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm A1 (177Lu-PSMA-617, iADT); Patients receive 177Lu-PSMA-617 IV once every 6 weeks and leuprolide acetate SC Q3M. Treatment continues for up to 6 months in the absence of disease progression or unacceptable toxicity. Patients also undergo PSMA PET/CT and collection of blood samples throughout the trial and undergo SPECT on study.	Other: Quality-of-Life Assessment; Ancillary studies; Other Names: Quality of Life Assessment; Procedure: Biospecimen Collection; Undergo collection of blood samples; Other Names: Biological Sample Collection; Biospecimen Collected; Specimen Collection; Sample Collection; Drug: Leuprolide Acetate; Given SC; Other Names: Enantone; LEUP; Lupron; Lupron Depot; Leuprorelin Acetate; A-43818; Abbott 43818; Abbott-43818; Carcinil; Depo-Eligard; Eligard; Enanton; Enantone-Gyn; Ginecrin; Leuplin; Lucrin; Lucrin Depot; Lupron Depot-3 Month; Lupron Depot-4 Month; Lupron Depot-Ped; Lutrate; Procren; Procrin; Prostap; TAP-144; Trenantone; Uno-Enantone; Viadur; Luprodex Depot; A 43818; A43818; Fensolvi; TAP 144; TAP144; Procedure: Single Photon Emission Computed Tomography; Undergo SPECT; Other Names: ST; Medical Imaging, Single Photon Emission Computed Tomography; Single Photon Emission Tomography; single-photon emission computed tomography; SPECT; SPECT imaging; SPECT SCAN; SPET; tomography, emission computed, single photon; Tomography, Emission-Computed, Single-Photon; Single-Photon Emission Computed; Drug: Lutetium Lu 177 Vipivotide Tetraxetan; Given IV; Other Names: 177Lu-labeled PSMA-617; 177Lu-PSMA-617; Pluvicto; Lu177-PSMA-617; Lutetium-177-PSMA-617; AAA 617; AAA-617; AAA617; Lutetium Lu 177-PSMA-617; LUTETIUM LU-177 VIPIVOTIDE TETRAXETAN; Procedure: PSMA PET-CT Scan; Undergo PSMA PET/CT; Other Names: PET-CT (PSMA); Prostate-specific Membrane Antigen PET-CT; PSMA PET-CT
Active Comparator: Arm A2 (iADT); Patients receive leuprolide acetate SC Q3M for up to 6 months in the absence of disease progression or unacceptable toxicity. Patients also undergo PSMA PET/CT and collection of blood samples throughout the trial.	Other: Quality-of-Life Assessment; Ancillary studies; Other Names: Quality of Life Assessment; Procedure: Biospecimen Collection; Undergo collection of blood samples; Other Names: Biological Sample Collection; Biospecimen Collected; Specimen Collection; Sample Collection; Drug: Leuprolide Acetate; Given SC; Other Names: Enantone; LEUP; Lupron; Lupron Depot; Leuprorelin Acetate; A-43818; Abbott 43818; Abbott-43818; Carcinil; Depo-Eligard; Eligard; Enanton; Enantone-Gyn; Ginecrin; Leuplin; Lucrin; Lucrin Depot; Lupron Depot-3 Month; Lupron Depot-4 Month; Lupron Depot-Ped; Lutrate; Procren; Procrin; Prostap; TAP-144; Trenantone; Uno-Enantone; Viadur; Luprodex Depot; A 43818; A43818; Fensolvi; TAP 144; TAP144; Procedure: PSMA PET-CT Scan; Undergo PSMA PET/CT; Other Names: PET-CT (PSMA); Prostate-specific Membrane Antigen PET-CT; PSMA PET-CT
Experimental: Arm B1 (177Lu-PSMA-617, iADT, iAA, P); Patients receive 177Lu-PSMA-617 IV every 6 weeks, leuprolide acetate SC Q3M, abiraterone acetate PO QD and prednisone PO BID. Treatment continues for up to 6 months in the absence of disease progression or unacceptable toxicity. Patients also undergo PSMA PET/CT and collection of blood samples throughout the trial and undergo SPECT on study.	Other: Quality-of-Life Assessment; Ancillary studies; Other Names: Quality of Life Assessment; Procedure: Biospecimen Collection; Undergo collection of blood samples; Other Names: Biological Sample Collection; Biospecimen Collected; Specimen Collection; Sample Collection; Drug: Prednisone; Given PO; Other Names: Deltasone; Orasone; .delta.1-Cortisone; 1, 2-Dehydrocortisone; Adasone; Cortancyl; Dacortin; DeCortin; Decortisyl; Decorton; Delta 1-Cortisone; Delta-Dome; Deltacortene; Deltacortisone; Deltadehydrocortisone; Deltison; Deltra; Econosone; Lisacort; Meprosona-F; Metacortandracin; Meticorten; Ofisolona; Panafcort; Panasol-S; Paracort; Perrigo Prednisone; PRED; Predicor; Predicorten; Prednicen-M; Prednicort; Prednidib; Prednilonga; Predniment; Prednisone Intensol; Prednisonum; Prednitone; Promifen; Rayos; Servisone; SK-Prednisone; Drug: Abiraterone Acetate; Given PO; Other Names: Zytiga; CB7630; Yonsa; BR9004; BR9004-1; JNJ-212082; CB-7630; CB 7630; Drug: Leuprolide Acetate; Given SC; Other Names: Enantone; LEUP; Lupron; Lupron Depot; Leuprorelin Acetate; A-43818; Abbott 43818; Abbott-43818; Carcinil; Depo-Eligard; Eligard; Enanton; Enantone-Gyn; Ginecrin; Leuplin; Lucrin; Lucrin Depot; Lupron Depot-3 Month; Lupron Depot-4 Month; Lupron Depot-Ped; Lutrate; Procren; Procrin; Prostap; TAP-144; Trenantone; Uno-Enantone; Viadur; Luprodex Depot; A 43818; A43818; Fensolvi; TAP 144; TAP144; Procedure: Single Photon Emission Computed Tomography; Undergo SPECT; Other Names: ST; Medical Imaging, Single Photon Emission Computed Tomography; Single Photon Emission Tomography; single-photon emission computed tomography; SPECT; SPECT imaging; SPECT SCAN; SPET; tomography, emission computed, single photon; Tomography, Emission-Computed, Single-Photon; Single-Photon Emission Computed; Drug: Lutetium Lu 177 Vipivotide Tetraxetan; Given IV; Other Names: 177Lu-labeled PSMA-617; 177Lu-PSMA-617; Pluvicto; Lu177-PSMA-617; Lutetium-177-PSMA-617; AAA 617; AAA-617; AAA617; Lutetium Lu 177-PSMA-617; LUTETIUM LU-177 VIPIVOTIDE TETRAXETAN; Procedure: PSMA PET-CT Scan; Undergo PSMA PET/CT; Other Names: PET-CT (PSMA); Prostate-specific Membrane Antigen PET-CT; PSMA PET-CT
Active Comparator: Arm B2 (iADT, iAA, P); Patients receive leuprolide acetate SC Q3M, abiraterone acetate PO QD and prednisone PO BID. Treatment continues for up to 6 months in the absence of disease progression or unacceptable toxicity. Patients also undergo PSMA PET/CT and collection of blood samples throughout the trial.	Other: Quality-of-Life Assessment; Ancillary studies; Other Names: Quality of Life Assessment; Procedure: Biospecimen Collection; Undergo collection of blood samples; Other Names: Biological Sample Collection; Biospecimen Collected; Specimen Collection; Sample Collection; Drug: Prednisone; Given PO; Other Names: Deltasone; Orasone; .delta.1-Cortisone; 1, 2-Dehydrocortisone; Adasone; Cortancyl; Dacortin; DeCortin; Decortisyl; Decorton; Delta 1-Cortisone; Delta-Dome; Deltacortene; Deltacortisone; Deltadehydrocortisone; Deltison; Deltra; Econosone; Lisacort; Meprosona-F; Metacortandracin; Meticorten; Ofisolona; Panafcort; Panasol-S; Paracort; Perrigo Prednisone; PRED; Predicor; Predicorten; Prednicen-M; Prednicort; Prednidib; Prednilonga; Predniment; Prednisone Intensol; Prednisonum; Prednitone; Promifen; Rayos; Servisone; SK-Prednisone; Drug: Abiraterone Acetate; Given PO; Other Names: Zytiga; CB7630; Yonsa; BR9004; BR9004-1; JNJ-212082; CB-7630; CB 7630; Drug: Leuprolide Acetate; Given SC; Other Names: Enantone; LEUP; Lupron; Lupron Depot; Leuprorelin Acetate; A-43818; Abbott 43818; Abbott-43818; Carcinil; Depo-Eligard; Eligard; Enanton; Enantone-Gyn; Ginecrin; Leuplin; Lucrin; Lucrin Depot; Lupron Depot-3 Month; Lupron Depot-4 Month; Lupron Depot-Ped; Lutrate; Procren; Procrin; Prostap; TAP-144; Trenantone; Uno-Enantone; Viadur; Luprodex Depot; A 43818; A43818; Fensolvi; TAP 144; TAP144; Procedure: PSMA PET-CT Scan; Undergo PSMA PET/CT; Other Names: PET-CT (PSMA); Prostate-specific Membrane Antigen PET-CT; PSMA PET-CT

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Radiographic progression free survival (rPFS)	Will be evaluated according to prostate specific membrane antigen (PSMA) positron emission tomography (PET) progression (PPP) criteria. Defined as the time from enrollment to documented radiographic progression or death from any cause, whichever occurs first.	At 18 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Biochemical recurrence free survival (BCR-FS)	Assessed using PSMA scans. Defined as the time after treatment during which no signs of biochemical recurrence are found.	At 12 months
Treatment-free interval	Defined as the length of time a patient remains off active systemic therapies while maintaining disease control.	Up to 18 months
Overall survival	Defined as the time from randomization or enrollment to death from any cause, whichever occurs first.	Up to 3 years

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Quality of life - FACT-P	Assessed using the Functional Assessment of Cancer Therapy-Prostate (FACT-P) questionnaire, a 39-item questionnaire used to measures Health-Related Quality of Life (HRQOL) in prostate cancer patients. Responses to each question are scored on a 5-point Likert scale ranging from 0 (not at all) to 4 (very much). Possible total scores range from 0-156, with higher scores indicating better QoL. A drop in the FACT-P total score >5 points will be considered clinically meaningful.	At baseline and then every 3 months up to 1 year

Collaborators and Investigators

• Sponsor: Mayo Clinic
• Investigators: Principal Investigator: Matthew K. Tollefson, MD, Mayo Clinic in Rochester

Publications and helpful links

Helpful Links

• Mayo Clinic Clinical Trials

Study record dates

Study Major Dates

• Study Start (Estimated): July 1, 2026
• Primary Completion (Estimated): December 30, 2030
• Study Completion (Estimated): December 30, 2030

Study Registration Dates

• First Submitted: June 10, 2026
• First Submitted That Met QC Criteria: June 10, 2026
• First Posted (Actual): June 16, 2026

Study Record Updates

• Last Update Posted (Actual): June 16, 2026
• Last Update Submitted That Met QC Criteria: June 10, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Urogenital Diseases; Genital Diseases; Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Prostatic Diseases; Male Urogenital Diseases; Prostatic Neoplasms; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Pituitary Hormone-Releasing Hormones; Hypothalamic Hormones; Peptide Hormones; Neuropeptides; Peptides; Amino Acids, Peptides, and Proteins; Oligopeptides; Nerve Tissue Proteins; Proteins; Investigative Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Physical Phenomena; Polycyclic Compounds; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Pregnadienediols; Electromagnetic Phenomena; Magnetic Phenomena; Androstenes; Androstanes; Electromagnetic Radiation; Radiation; Radiation, Ionizing; Elementary Particles; Light; Optical Phenomena; Radiation, Nonionizing; Gonadotropin-Releasing Hormone; Abiraterone Acetate; Pluvicto; Prednisone; Leuprolide; luprolide acetate gel depot; Specimen Handling; X-Rays; Photons; deltacortene; prednylidene
• Other Study ID Numbers: MC250507; 25-008953 (Other Identifier: Mayo Clinic Institutional Review Board); SPARKLE (Other Identifier: Mayo Clinic Urology)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No