Lutetium-177 (Lu177) Prostate-Specific Antigen (PSMA)-Directed EndoRadiotherapy

NCT03042312 | Terminated Phase 2 Results DMC FDA Drug

• 2 other identifiers: PSMA-617-02133661
• Study Type: interventional
• Target: 71
• Locations: 1 country
• Sites: 2

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.

Conditions

Metastatic Castration Resistant Prostate Cancer

Outcome Measures

Primary Outcomes (2)

• Number of Participants With Treatment Emergent Adverse Events

  Treatment-emergent adverse events (TEAEs) were collected from first dosing 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. The distribution of adverse events was done via the analysis of frequencies for treatment emergent Adverse Event (TEAEs), Serious Adverse Event (TESAEs) and Deaths due to AEs, through the monitoring of relevant clinical and laboratory safety parameters. Only descriptive analysis performed.

  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

• Number of Participants Achieving PSA Response at Week 12

  PSA response was defined as the proportion of patients who had a \>= 50% decrease in PSA from Baseline at Week 12.

  Week 12

Secondary Outcomes (8)

• Percent Change in PSA From Baseline to Week 12

  Week 12

• Maximum Percent Change in PSA Response

  Every 6 weeks during the treatment and every 3 (+/- 1) months after last treatment until reaching endpoint or 24 months after the first treatment

• PSA Progression and Death Events

  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

• RECIST 1.1 Overall Response by Follow-up Assessment Visit

  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.

• RECIST 1.1 Disease Control Rate by Follow-up Assessment Visit

  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.

Study Arms (2)

177Lu-PSMA-617 (6.0 GBq)

EXPERIMENTAL

Repeated i.v. application of 6.0 GBq (gigabequerel)(+/- 10%, arm 1) every 8+/- 1 weeks; RLT until reaching four cycles or threshold maximum dose to the kidneys of 23 Gy as determined by dosimetry

Drug: 177Lu-PSMA-617

177Lu-PSMA-617 (7.4 GBq)

EXPERIMENTAL

Repeated i.v. application of 7.4 GBq (gigabequerel)(+/- 10%, arm 2) of drug every 8+/- 1 weeks; RLT until reaching four cycles or threshold maximum dose to the kidneys of 23 Gy as determined by dosimetry

Drug: 177Lu-PSMA-617

Interventions

177Lu-PSMA-617 DRUG

Lutetium (177Lu) -DOTA (1,4,7,10-tetra-azacyclododecane-N,N',N'',N'''-tetraacetic acid )-PSMA has three components: PSMA is the targeting vector , DOTA (1, 4, 7, 10-tetraazacyclododecane-1, 4, 7, 10-tetraacetic acid) is a radiometal chelator and a linking group, and 177Lu is the beta emitter that upon internalization delivers radiation to the nucleus of tumor cells to cause DNA damage. The targeting vector utilizes glu-urea-lys sequence which is an inhibitor capable of binding to the domain of PSMA. These components have been previously used in human subjects and in medical research.

Also known as: Lu177 RLT

177Lu-PSMA-617 (6.0 GBq); 177Lu-PSMA-617 (7.4 GBq)

Eligibility Criteria

• Age: 18 Years+
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Prostate cancer proven by histopathology
• Unresectable metastases
• Progressive disease, both docetaxel naive and docetaxel treated.
• Castration resistant disease with confirmed testosterone level ≤50 ng/ml under prior androgen deprivation therapy (ADT)
• Positive 68Ga-PSMA-11 PET/CT (positron emission computed tomography ) or diagnostic 177Lu-PSMA-617 scintigraphy
• ECOG 0-2
• 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
• Signing of the Informed Consent Form
• Patients enrolling in this trail should have received either Enzalutamide or Abiraterone

You may not qualify if:

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

Sponsors & Collaborators

• Endocyte: lead

Study Sites (2)

David Geffen School of Medicine at UCLA

Los Angeles, California, 90095, United States

Location

Excel Diagnostics and Nuclear Oncology Center

Houston, Texas, 77042, United States

Location

Related Publications (1)

• 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.

  PMID: 34246328 DERIVED

MeSH Terms

Interventions

Pluvicto

Limitations and Caveats

The study began on 05-Jul-17 as an Investigator Initiated Trial and sponsorship was transferred to Endocyte on 01-Jun-18. Recruitment was stopped before the target sample size was achieved based on strategic considerations.

Results Point of Contact

• Title: Study Director
• Organization: Novartis Pharmaceuticals

Novartis.email@novartis.com

862-778-8300

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 18, 2017
• First Posted: February 3, 2017
• Study Start: July 12, 2017
• Primary Completion: January 15, 2020
• Study Completion: January 15, 2020
• Last Updated: March 24, 2021
• Results First Posted: March 24, 2021

Record last verified: 2021-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)