SPLASH (MCRPC, 2e lijn))

SPLASH onderzoekt  Lutetium-PSMA voorafgaande aan chemotherapie. Het betreft dus patiënten met hormoontherapie en vervolgens mCRPC en ziekteprogressie na een ARSI ( abiraterone of enzalutamide). Patiënten worden gerandomiseerd tussen Lutetium-PSMA en een cross-over naar de ARSI die ze nog niet hebben gehad. We weten uit CARD dat die cross-over niet erg zinvol is, maar het goede aspect is dat patiënten in die ARSI cross-over arm mogen overstappen naar Lutetium-PSMA zodra is vastgesteld dat de ziekte daadwerkelijk (radiologisch) progressief is. Uit CARD weten we dat dit vaak al na 12 weken vast te stellen is. Bovendien is de verdeling bij de randomisatie 2:1, dus de kans om gelijk in de Lutetium groep terecht te komen, is twee keer groter dan in de hormoon-cross-over groep.

SPLASH is daarmee een zeer geschikte studie voor patiënten die in aanmerking willen komen voor een Lutetium behandeling VOORAFGAANDE aan de huidige reguliere behandeling met  docetaxel en cabazitaxel.

Studie SPLASH is open in:  ErasmusMC (prof. De Wit), Radboudumc (dr. Van Gemert ), St Antonius Ziekenhuis (dr. Lavalaye).

Inclusion criteria

  1. Male age ≥ 18 yrs.
  2. Histologic, pathologic and/or cytologic adenocarcinoma of the prostate
  3. Ineligible or averse to chemotherapeutic options
  4. Progressive mCRPC based on at least one of the following:
    • Serum/plasma PSA progression defined as increase in PSA greater than 25% and >2 ng/mL above nadir, confirmed by progression at 2 time points at least 3 weeks apart.
    • Soft-tissue progression defined as an increase ≥20% in the sum of the diameter (SOD) (short axis for nodal lesions and long axis for non-nodal lesions) of all target lesions based on the smallest SOD since treatment started or the appearance of 1 or a new lesion.
    • Progression of bone disease: evaluable disease or one new bone lesion by bone scan.
  5. Progression on previous treatment with one ARAT (abiraterone, enzalutamide, darolutamide, apalutamide) in either the CSPC or CRPC setting
    • Patient must washout of the ARAT for 4 weeks if randomized to 177Lu
    • PSMA PET scan positive as determined by central read

6. Castrate testosterone levels (<1.7 nmol/L or <50 ng/dL)

7. Adequate organ function based on protocol specified lab values

8. HIV at low risk of AIDs-related outcomes allowed

9. Partners with childbearing potential: use barrier protection on-study & 6 mo. post-study

10. Willing to initiate ARAT therapy (either Enzalutamide or Abiraterone), pre-specified by investigator, if randomized to Arm B (not applicable to dosimetry patients)

11. ECOG: 0-1

12. Willing/able to comply with study requirements

13. Signed ICF

 

Exclusion criteria

  1. If noted on pathology report, Prostate Cancer (PCa) with (>10% present in cells) sarcomatoid, spindle cell, small-cell or neuroendocrine  component
  2. Prior PCa therapy ≤28 d. (exclusion: 1st line EBRT, ARAT, LHRH agonist or antagonist , non-radioactive bone targeting agents)
  1. Prior cytotoxic chemotherapy for CRPC (chemotherapy for HSPC allowed if last dose >1 year prior to consent)
  2. Prior systemic radionuclides (e.g. radium 223, rhenium 186, strontium-89).
  3. Prior immunotherapy (exception: sipuleucel-T [Provenge®])
  4. Prior PSMA-targeted radioligand therapy, e.g., Lu-177-PSMA-617, I 131-1095.
  5. Poly ADP ribose polymerase (PARP) inhibitor for prostate cancer
  6. Patients who progressed on 2 or more prior lines of ARAT therapy
  7. Patients on bone targeted therapy who are not on a stable dose for at least 4 weeks prior to randomization
  8. Administration of an investigational therapy ≤ 60 days or 5 half-lives (whichever is shorter)
  9. Major surgery ≤ 30 d.
  10. Life expectancy < 6 mo.
  11. Liver mets > 1 cm
  12. Superscan on Bone Scan
  13. Opioid use for cancer-related pain ≤30 days prior to consent
  14. CNS mets
  15. Contraindications to the use of planned ARAT therapy
  16. Active malignancy excluding low-grade non-muscle-invasive bladder Ca & non-melanoma skin Ca
  17. Concurrent illness that jeopardizes study participation
  18. Serious psychological, familial, sociological, or geographical condition jeopardizing protocol compliance
  19. Symptomatic or impending cord compression
  20. Concurrent serious illnesses (ex. class III/IV CHF, prolonged QT, uncontrolled infection, active hepatitis) that would impair study participation/cooperation.