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
3 other identifiers
interventional
202
1 country
1
Brief Summary
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_2
Started Jul 2026
Typical duration for phase_2
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
June 10, 2026
CompletedFirst Posted
Study publicly available on registry
June 16, 2026
CompletedStudy Start
First participant enrolled
July 1, 2026
CompletedPrimary Completion
Last participant's last visit for primary outcome
December 30, 2030
ExpectedStudy Completion
Last participant's last visit for all outcomes
December 30, 2030
June 17, 2026
June 1, 2026
4.5 years
June 10, 2026
June 15, 2026
Conditions
Outcome Measures
Primary Outcomes (1)
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 Outcomes (3)
Biochemical recurrence free survival (BCR-FS)
At 12 months
Treatment-free interval
Up to 18 months
Overall survival
Up to 3 years
Other Outcomes (1)
Quality of life - FACT-P
At baseline and then every 3 months up to 1 year
Study Arms (4)
Arm A1 (177Lu-PSMA-617, iADT)
EXPERIMENTALPatients receive 177Lu-PSMA-617 IV once every 6 weeks and leuprolide acetate subcutaneous (SC) once every 3 months (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.
Arm A2 (iADT)
ACTIVE COMPARATORPatients 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.
Arm B1 (177Lu-PSMA-617, iADT, iAA, P)
EXPERIMENTALPatients receive 177Lu-PSMA-617 IV every 6 weeks, leuprolide acetate SC Q3M, abiraterone acetate PO (by mouth) QD (once a day) and prednisone PO BID (twice a day). 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.
Arm B2 (iADT, iAA, P)
ACTIVE COMPARATORPatients 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.
Interventions
Given SC
Given PO
Given PO
Undergo collection of blood samples
Given IV
Undergo PSMA PET/CT
Ancillary studies
Undergo SPECT
Eligibility Criteria
You may qualify if:
- 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
- +8 more criteria
You may not qualify if:
- 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
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Mayo Cliniclead
Study Sites (1)
Mayo Clinic in Rochester
Rochester, Minnesota, 55905, United States
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Matthew K. Tollefson, MD
Mayo Clinic in Rochester
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
June 10, 2026
First Posted
June 16, 2026
Study Start
July 1, 2026
Primary Completion (Estimated)
December 30, 2030
Study Completion (Estimated)
December 30, 2030
Last Updated
June 17, 2026
Record last verified: 2026-06