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Study Evaluating mCRPC Treatment Using PSMA [Lu-177]-PNT2002 Therapy After Second-line Hormonal Treatment (SPLASH)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT04647526
Recruitment Status : Recruiting
First Posted : December 1, 2020
Last Update Posted : September 21, 2021
Information provided by (Responsible Party):
POINT Biopharma

Brief Summary:
The purpose of this study is to evaluate the efficacy and safety of [Lu-177]-PNT2002 in patients with metastatic castration-resistant prostate cancer who have progressed following treatment with androgen receptor axis-targeted therapy (ARAT).

Condition or disease Intervention/treatment Phase
Metastatic Castration-Resistant Prostate Cancer Drug: [Lu-177]-PNT2002 Drug: Abiraterone Drug: Enzalutamide Phase 3

Detailed Description:

The primary objective of the study is to determine the efficacy of [Lu-177]-PNT2002 ([Lu-177]-PSMA-I&T) versus abiraterone or enzalutamide in delaying radiographic progression in patients with mCRPC.

The study consists of 3 phases: Dosimetry, Randomized Treatment, and Long term Follow up.

The study will commence with a 25-patient safety and dosimetry lead-in (Part 1) and proceed to a randomization treatment phase in approximately 390 patients (Part 2). Patients in Part 2 will be randomized in a 2:1 ratio to receive either [Lu-177]-PNT2002 (Arm A), or enzalutamide or abiraterone (Arm B). Patients in Arm B who experience radiographic progression per central review and meet protocol defined eligibility, may crossover to receive [Lu-177]-PNT2002. All patients will be followed in long-term follow-up for at least 5 years from the first therapeutic dose, death, or loss to follow up (Part 3).

Only patients that meet PSMA PET avidity criteria per central review will be eligible for this study.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 415 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 3, Open-Label, Randomized Study Evaluating Metastatic Castrate Resistant Prostate Cancer Treatment Using PSMA [Lu-177]-PNT2002 Therapy After Second-line Hormonal Treatment (SPLASH)
Actual Study Start Date : February 25, 2021
Estimated Primary Completion Date : March 2023
Estimated Study Completion Date : March 2028

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Prostate Cancer

Arm Intervention/treatment
Experimental: [Lu-177]-PNT2002 (Arm A)
[Lu-177]-PNT2002 (6.8 GBq (±10%) every 8 weeks for 4 cycles)
Drug: [Lu-177]-PNT2002
Participants randomized to Arm A will receive 6.8 GBq (±10%) of [Lu-177]-PNT2002 every 8 weeks for 4 cycles
Other Name: [Lu-177]-PSMA-I&T

Active Comparator: Control Arm (Arm B)
Abiraterone (1000 mg orally qd with: 5 mg bid prednisone or 0.5 mg qd dexamethasone) or enzalutamide (160 mg orally qd).
Drug: Abiraterone
Abiraterone (1000 mg orally qd with: 5 mg bid prednisone or 0.5 mg qd dexamethasone)

Drug: Enzalutamide
Enzalutamide (160 mg orally qd)

Primary Outcome Measures :
  1. Radiographic Progression Free Survival (rPFS) [ Time Frame: 32 weeks ]
    Time in months from the date of randomization to radiological progression by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 (soft tissue) or confirmed progression on bone scan assessed by Prostate Cancer Working Group 3 (PCWG3) (bone), or death from any cause, as assessed by blinded independent central review (BICR).

Secondary Outcome Measures :
  1. Objective Response Rate (ORR) [ Time Frame: 32 weeks ]
    Proportion of patients with partial or complete response (PR or CR, respectively) by BICR based on RECIST 1.1 criteria (soft tissue) and PCWG3 criteria (bone).

  2. Duration of response [ Time Frame: 32 weeks ]
    Time from the first date of CR or PR by BICR to the first occurrence of radiographic progression (PD) by BICR based on PCWG3 modified RECIST 1.1.

  3. Overall Survival [ Time Frame: 5 years ]
    Time from the date of randomization until death due to any cause.

  4. PSA Response [ Time Frame: 32 weeks ]
    Proportion of patients achieving a ≥50% decrease in PSA (PCWG3 criteria) from baseline to the lowest post-baseline PSA result, confirmed by a second consecutive PSA assessment at least 3 weeks later.

  5. Biochemical Progression-Free Survival (bPFS) [ Time Frame: 32 weeks ]
    Time from randomization to the date of the first PSA increase from baseline ≥25% and ≥2 ng/mL above nadir confirmed by a second PSA measurement defining progression ≥3 weeks later, as per PCWG3.

Other Outcome Measures:
  1. Safety and Tolerability (AEs) [ Time Frame: 5 years ]
    Frequency and severity of AEs, graded and categorized using CTCAE v. 5.0.

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  1. Male aged 18 years or older.
  2. Histological, pathological, and/or cytological confirmation of adenocarcinoma of the prostate.
  3. Ineligible or averse to chemotherapeutic treatment options.
  4. Patients must have progressive mCRPC at the time of consent based on at least 1 of the following criteria:

    1. 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.
    2. 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 one or a new lesion.
    3. Progression of bone disease: evaluable disease or one new bone lesion by bone scan
  5. Previous treatment with one ARAT (abiraterone or enzalutamide or darolutamide or apalutamide) in either the CSPC or CRPC setting.
  6. PSMA-PET scan (i.e., 68Ga-PSMA-11 or 18F-DCFPyL) positive as determined by the sponsor's central reader.
  7. Castrate circulating testosterone levels (<1.7 nmol/L or <50 ng/dL).
  8. Adequate organ function, independent of transfusion:

    a. Bone marrow reserve: i. White blood cell (WBC) count ≥2.5 × 109/L OR absolute neutrophil count (ANC) ≥1.5 × 109/L.

    ii. Platelets ≥100 × 109/L. iii. Hemoglobin ≥8 mmol/L. b. Liver function: i. Total bilirubin ≤1.5 × institutional upper limit of normal (ULN). For patients with known Gilbert's syndrome, ≤3 × ULN is permitted.

    ii. ALT or AST ≤3.0× ULN. c. Renal function: i. Serum/plasma creatinine ≤1.5 × ULN or creatinine clearance ≥50 mL/min based on Cockcroft-Gault formula.

    d. Albumin ≥30 g/L.

  9. Human immunodeficiency virus-infected patients who are healthy and have a low risk of acquired immunodeficiency syndrome-related outcomes are included in this trial.
  10. For patients who have partners of childbearing potential: Partner and/or patient must use a method of birth control with adequate barrier protection, deemed acceptable by the principal investigator during the study and for 6 months after last study drug administration.
  11. Willing to initiate ARAT therapy (either enzalutamide or abiraterone), pre-specified by investigator, if randomized to Treatment Arm B.
  12. ECOG performance status 0 to 1.
  13. Willing and able to comply with all study requirements and treatments (including 177Lu PNT2002) as well as the timing and nature of required assessments.
  14. Signed informed consent.

Exclusion Criteria:

Patients are excluded from the study if any of the following criteria apply:

  1. Prostate cancer with known significant (>10%) sarcomatoid or spindle cell or neuroendocrine components. Any small cell component in the cancer should result in exclusion.
  2. Prior treatment for prostate cancer ≤28 days prior to randomization, with the exclusion of first-line local external beam, ARAT, luteinizing hormone-releasing hormone (LHRH) therapy, or non-radioactive bone-targeted agents.
  3. Any prior cytotoxic chemotherapy for CRPC (e.g., cabazitaxel or docetaxel); chemotherapy for hormone-sensitive prostate cancer (HSPC) is allowed if the last dose was administered >1 year prior to consent.
  4. Prior treatment with systemic radionuclides (e.g. radium-223, rhenium-186, strontium 89).
  5. Prior immuno-therapy, except for sipuleucel-T.
  6. Prior PSMA-targeted radioligand therapy, e.g., Lu-177-PSMA-617, I 131-1095.
  7. Prior poly ADP ribose polymerase (PARP) inhibitor for prostate cancer.
  8. Patients who have had 2 or more lines of ARATs.
  9. Patients receiving bone-targeted therapy (e.g. denosumab, zoledronic acid) must be on stable doses for at least 4 weeks prior to randomization.
  10. Administration of an investigational agent ≤60 days or 5 half-lives, whichever is shorter, prior to randomization.
  11. Major surgery ≤30 days prior to randomization.
  12. Estimated life expectancy <6 months as assessed by the principal investigator.
  13. Presence of liver metastases >1 cm on abdominal imaging.
  14. A superscan on bone scan defined as a bone scan that demonstrates markedly increased skeletal radioisotope uptake relative to soft tissues in association with absent or faint genitourinary tract activity71.
  15. Use of opioids for cancer-related pain ≤30 days prior to consent.
  16. Known presence of central nervous system metastases.
  17. Contraindications to the use of planned ARAT therapy.
  18. Active malignancy other than low-grade non-muscle-invasive bladder cancer and non melanoma skin cancer.
  19. Concurrent illness that may jeopardize the patient's ability to undergo study procedures.
  20. Serious psychological, familial, sociological, or geographical condition that might hamper compliance with the study protocol and follow-up schedule. Patients that travel need to be capable of repeated visits even if they are on the control arm.
  21. Symptomatic cord compression, or clinical or radiologic findings indicative of impending cord compression.
  22. Concurrent serious (as determined by the investigator) medical conditions, including, but not limited to, New York Heart Association class III or IV congestive heart failure (see 12.1 Appendix 1), unstable ischemia, uncontrolled symptomatic arrhythmia, history of congenital prolonged QT syndrome, 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT04647526

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Contact: Richard Cioci +1-833-544-2637 ext 202

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United States, California
VA Greater Los Angeles Healthcare System Active, not recruiting
Los Angeles, California, United States, 90073
United States, Maryland
Chesapeake Urology Associates (CUA) P.A. Active, not recruiting
Towson, Maryland, United States, 21204
United States, Michigan
University of Michigan Hospitals Active, not recruiting
Ann Arbor, Michigan, United States, 48109
United States, Missouri
VA St. Louis Health Care System Active, not recruiting
Saint Louis, Missouri, United States, 63106
Saint Louis University Hospital Active, not recruiting
Saint Louis, Missouri, United States, 63110
Washington University School of Medicine Active, not recruiting
Saint Louis, Missouri, United States, 63110
United States, Nebraska
Urology Cancer Center, PC Active, not recruiting
Omaha, Nebraska, United States, 68130
United States, New York
New York Presbyterian Hospital/Weill Cornell Medical Center Active, not recruiting
New York, New York, United States, 10065
United States, Pennsylvania
Fox Chase Cancer Center Active, not recruiting
Philadelphia, Pennsylvania, United States, 19111
United States, Texas
Excel Diagnostics & Nuclear Oncology Center Active, not recruiting
Houston, Texas, United States, 77402
Canada, Ontario
Princess Margaret Cancer Centre Recruiting
Toronto, Ontario, Canada, M5G 2M9
Canada, Quebec
Jewish General Hospital Recruiting
Montreal, Quebec, Canada, H3T 1E2
CHU of Quebec - Laval University Recruiting
Quebec City, Quebec, Canada, G1R 2J6
Sponsors and Collaborators
POINT Biopharma
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Study Director: Jessica Jensen POINT Biopharma
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Responsible Party: POINT Biopharma Identifier: NCT04647526    
Other Study ID Numbers: PBP-301
First Posted: December 1, 2020    Key Record Dates
Last Update Posted: September 21, 2021
Last Verified: September 2021

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by POINT Biopharma:
Prostate cancer
radioligand therapy
Additional relevant MeSH terms:
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Prostatic Neoplasms
Genital Neoplasms, Male
Urogenital Neoplasms
Neoplasms by Site
Prostatic Diseases