Open-label study comparing 177Lu-PSMA-617 vs. a change of androgen receptor-directed therapy drugs in the treatment of mCRPC.

Phase 1

• Conditions: PSMA-positive metastatic castration-resistant prostate cancer; MedDRA version: 21.1Level: LLTClassification code 10076506Term: Castration-resistant prostate cancerSystem Organ Class: 100000004864; Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2020-003969-19-CZ
• Lead Sponsor: ovartis Pharma AG

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2021-03-03
• Last Update Posted: 26 February 2024

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: Male
• Target Recruitment: 450

Inclusion Criteria

1. Signed informed consent must be obtained prior to participation in the study
2. Participants must be adults = 18 years of age
3. Participants must have an ECOG performance status of 0 to 1
4. Participants must have histological pathological, and/or cytological confirmation of adenocarcinoma of the prostate
5. Participants must be 68Ga-PSMA-11 PET/CT scan positive, and eligible as determined by the sponsor’s central reader
6. Participants must have a castrate level of serum/plasma testosterone (< 50 ng/dL or < 1.7 nmol/L)
7. Participants must have received one prior approved ARDT (for example, abiraterone, enzalutamide, darolutamide, or apalutamide, etc.) and have documented progression on therapy
8. Participants must have progressive mCRPC. Documented progressive mCRPC will be based on at least 1 of the following criteria:
- Serum/plasma PSA progression defined as 2 consecutive increases in PSA over a previous reference value measured at least 1 week prior. The minimal start value is 2.0 ng/mL
- Soft-tissue progression defined [PCWG3-modified RECIST v1.1 (Eisenhauer et al 2009, Scher et al 2016)]
- Progression of bone disease: evaluable disease or one or more new bone lesions(s) by bone scan (PCWG3 criteria (Scher et al 2016))
9. Participants must have = 1 metastatic lesion that is present on screening/baseline CT, MRI, or bone scan imaging obtained = 28 days prior to beginning study therapy
10. Participants must have recovered to = Grade 2 from all clinically significant toxicities related to prior therapies (i.e. prior chemotherapy, radiation, etc.) except alopecia

Other protocol-defined inclusion criteria may apply
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 135
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 315

Exclusion Criteria

1. Previous treatment with any of the following within 6 months of randomization: Strontium-89, Samarium-153, Rhenium-186, Rhenium-188, Radium-223, hemi-body irradiation
2. Previous PSMA-targeted radioligand therapy
3. Prior treatment with cytotoxic chemotherapy for castration resistant or castrate sensitive prostate cancer (e.g., taxanes, platinum, estramustine, vincristine, methotrexate, etc.), immunotherapy or biological therapy [including monoclonal antibodies]) [Note: Taxane exposure (maximum 6 cycles) in the adjuvant or neoadjuvant setting is allowed if 12 months have elapsed since completion of this adjuvant or neoadjuvant therapy]
4. Any investigational agents within 28 days prior to day of randomization
5. Known hypersensitivity to any of the study treatments or its excipients or to drugs of similar classes
6. Other concurrent cytotoxic chemotherapy, immunotherapy, radioligand therapy, or investigational therapy
7. Transfusion or use of bone marrow stimulating agents for the sole purpose of making a participant eligible for study inclusion
8. Patients with a history of CNS metastases that are neurologically unstable, symptomatic, or receiving corticosteroids for the purpose of maintaining neurologic integrity. Participants with CNS metastases are eligible if received therapy (surgery, radiotherapy, gamma knife), asymptomatic and neurologically stable without corticosteroids. Participants with epidural disease, canal disease and prior cord involvement are eligible if those areas have been treated, are stable, and not neurologically impaired.
9. Symptomatic cord compression, or clinical or radiologic findings indicative of impending cord compression
10. History or current diagnosis of the following ECG abnormalities indicating significant risk of safety for study participants:
- Concomitant clinically significant cardiac arrhythmias, e.g. sustained ventricular tachycardia, complete left bundle branch block, high-grade AV block (e.g., bifascicular block, Mobitz type II and third degree AV block)
- History of familial long QT syndrome or known family history of Torsades de Pointe
- Cardiac or cardiac repolarization abnormality, including any of the following: History of myocardial infarction (MI), angina pectoris, or CABG within 6 months prior to starting study treatment

other protocol-defined exclusion criteria may apply

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified