Clinical trial NCT03042312: Lutetium-177 (Lu177) Prostate-Specific Antigen (PSMA)-Directed EndoRadiotherapy
Official title: PSMA-directed endoRadiothErapy of Castration-reSISTant Prostate Cancer (RESIST-PC). A Phase II Clinical Trial
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Metastatic Castration Resistant Prostate Cancer
Lead sponsor: Endocyte
Sponsor class: INDUSTRY
First posted: 2017-02-03
Enrollment: 71
Sex: MALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This was an open-label, multicenter, prospective trial to assess safety and efficacy of 177Lu-PSMA-617 in patients with metastatic castration resistant prostate cancer.

Detailed description: Upon inclusion patients were randomized in a 1:1 ratio into two treatment doses. Radioligand therapy (RLT) were performed by repeated intravenous (i.v.) injection of 6.0 gigabecquerel (GBq) (+/- 10%) or 7.4 GBq (+/- 10%) 177Lu-PSMA-617 every 8+/- 1 weeks until reaching four cycles or threshold maximum dose to the kidneys of 23 Gray (Gy). All doses after labeling were presented in buffered solution for i.v. injection.

In the initial plan for the study design a total of 200 patients with histologically proven prostate cancer and metastatic castration-resistant prostate cancer (mCRPC) were to be enrolled, however due to early stopping of enrollment only 71 patients were enrolled at time of data base lock. Each patient underwent a screening visit within 14 days prior to receiving study drug. Treatment was continued until either of the following conditions applied:

* Prostate-specific antigen (PSA)/radiographic progression at \>= 12 weeks
* Completion of four RLT cycles
* 23 Gy kidney dose would be exceeded by the next cycle as estimated by dosimetry
* Patient withdrawal (e.g. appearance of intolerable adverse events).

Eligibility criteria: Inclusion Criteria:

1. Prostate cancer proven by histopathology
2. Unresectable metastases
3. Progressive disease, both docetaxel naive and docetaxel treated.
4. Castration resistant disease with confirmed testosterone level ≤50 ng/ml under prior androgen deprivation therapy (ADT)
5. Positive 68Ga-PSMA-11 PET/CT (positron emission computed tomography ) or diagnostic 177Lu-PSMA-617 scintigraphy
6. ECOG 0-2
7. Sufficient bone marrow capacity as defined by WBC (white blood cell ) ≥2.500/μl, PLT (platelet) count ≥100.000/μl, Hb≥9.9 g/dl and ANC≥1500 mm3 for the first cycle and WBC≥2.000/ μl,PLT count ≥75.000/μl, Hb≥8.9 g/dl and ANC≥1000 mm3 for the subsequent cycles
8. Signing of the Informed Consent Form
9. Patients enrolling in this trail should have received either Enzalutamide or Abiraterone

Exclusion Criteria:

1. Less than 6 weeks since last myelosuppressive therapy (including Docetaxel, Cabazitaxel, 223Ra, 153Sm) or other radionuclide therapy.
2. Glomerular Filtration Rate (GFR) \<40 ml/min
3. Serum creatinine \> 1.5 ULN
4. AST and ALT\>5xULN
5. Urinary tract obstruction or marked hydronephrosis
6. Diffuse bone marrow involvement confirmed by super-scans

Primary outcomes:
measure: Number of Participants With Treatment Emergent Adverse Events
timeFrame: From first dosing (Day 0) up to last follow-up visit or until the event has resolved to baseline grade or better or the event was assessed stable by the investigator or the patient was lost to follow-up or withdrew consent, up to 24 months
measure: Number of Participants Achieving PSA Response at Week 12
timeFrame: Week 12
Secondary outcomes:
measure: Percent Change in PSA From Baseline to Week 12
timeFrame: Week 12
measure: Maximum Percent Change in PSA Response
timeFrame: Every 6 weeks during the treatment and every 3 (+/- 1) months after last treatment until reaching endpoint or 24 months after the first treatment
measure: PSA Progression and Death Events
timeFrame: Date of randomization to the date of first documented PSA progression or death, whichever occurs first, reported between day of first patient randomized up to 24 months after the first treatment
measure: RECIST 1.1 Overall Response by Follow-up Assessment Visit
timeFrame: Before 3rd radioligand therapy (RLT) cycle, and then every 3 (+/- 1) months after last treatment dose until disease progression or 24 months after the first treatment dose.
measure: RECIST 1.1 Disease Control Rate by Follow-up Assessment Visit
timeFrame: Before 3rd radioligand therapy (RLT) cycle, and then every 3 (+/- 1) months after last treatment dose until disease progression or 24 months after the first treatment dose.
measure: Prostate Cancer Working Group 3 (PCWG3) Bone Scan Clinical Impression by Visit
timeFrame: Screening, Week 8, Week 10, Week 16, Week 18, Week 22, Week 24, Follow-up Week 4, Follow-up Week 6, Follow-up Week 8
measure: Change From Baseline in Expanded Prostate Cancer Index Composite Short Form (EPIC-26)
timeFrame: Baseline, Month 3, Month 6, Follow-up Month 3
measure: Change From Baseline in Eastern Cooperative Oncology Group (ECOG) Performance Status
timeFrame: Baseline, Treatment Visit 1, Treatment Visit 2, Treatment Visit 3, Treatment Visit 4, Follow-up Month 3, Follow-up Month 12, Follow-up Month 15
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: David Geffen School of Medicine at UCLA
state: California
city: Houston
country: United States
facility: Excel Diagnostics and Nuclear Oncology Center
state: Texas
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References:
citation: Gafita A, Calais J, Grogan TR, Hadaschik B, Wang H, Weber M, Sandhu S, Kratochwil C, Esfandiari R, Tauber R, Zeldin A, Rathke H, Armstrong WR, Robertson A, Thin P, D'Alessandria C, Rettig MB, Delpassand ES, Haberkorn U, Elashoff D, Herrmann K, Czernin J, Hofman MS, Fendler WP, Eiber M. Nomograms to predict outcomes after 177Lu-PSMA therapy in men with metastatic castration-resistant prostate cancer: an international, multicentre, retrospective study. Lancet Oncol. 2021 Aug;22(8):1115-1125. doi: 10.1016/S1470-2045(21)00274-6. Epub 2021 Jul 8.