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

NCT ID: NCT03042312

Last Updated: 2021-03-24

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 71 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-07-12
• Study Completion Date: 2020-01-15

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).

Conditions

Metastatic Castration Resistant Prostate Cancer

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

177Lu-PSMA-617 (6.0 GBq)

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

Group Type: EXPERIMENTAL

177Lu-PSMA-617

Intervention Type: 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.

177Lu-PSMA-617 (7.4 GBq)

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

Group Type: EXPERIMENTAL

177Lu-PSMA-617

Intervention Type: 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.

Interventions

177Lu-PSMA-617

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.

Intervention Type: DRUG

Other Intervention Names

Lu177 RLT

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: No

Sponsors

Endocyte

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Novartis Pharmaceuticals

Role: STUDY_DIRECTOR

Novartis Pharmaceuticals

Locations

David Geffen School of Medicine at UCLA

Los Angeles, California, United States

Excel Diagnostics and Nuclear Oncology Center

Houston, Texas, United States

Countries

United States

References

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.

Reference Type: DERIVED

PMID: 34246328 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

133661

Identifier Type: OTHER

Identifier Source: secondary_id

PSMA-617-02

Identifier Type: -

Identifier Source: org_study_id