Open study comparing ¹⁷⁷Lu-PSMA-617 to a change of androgen receptor-directed treatment in the treatment of metastatic castration-resistant prostate cancer

Austria, Belgium, Canada, Czechia, France, Germany, Netherlands, Poland, Slovakia, Spain, Sweden, Switzerland, United Kingdom, United States (ICTRP)

ICTRP Studien-ID
NCT04689828 (ICTRP)

Offizieller Titel (Genehmigt von der Ethikkommission)
PSMAfore: A phase III, Open-label, Multi-Center, Randomized Study Comparing 177Lu-PSMA-617 vs. a Change of androgen receptor-directed therapy in the Treatment of Taxane Naïve Men with Progressive Metastatic Castrate Resistant Prostate Cancer (BASEC)

Wissenschaftlicher Titel
PSMAfore: A Phase III, Open-label, Multi-Center, Randomized Study Comparing 177Lu-PSMA-617 vs. a Change of Androgen Receptor-directed Therapy in the Treatment of Taxane Nave Men With Progressive Metastatic Castrate Resistant Prostate Cancer (ICTRP)

Öffentlicher Titel
177Lu-PSMA-617 vs. Androgen Receptor-directed Therapy in the Treatment of Progressive Metastatic Castrate Resistant Prostate Cancer (ICTRP)

Untersuchte Krankheit(en)
Prostatic Neoplasms (ICTRP)

Untersuchte Intervention
Drug: 177Lu-PSMA-617Drug: 68Ga-PSMA-11Drug: ARDTOther: Best supportive care (ICTRP)

Studientyp
Interventional (ICTRP)

Studiendesign
Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: Single (Outcomes Assessor). (ICTRP)

Ein-/Ausschlusskriterien
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).

7a. Participants must have progressed only once on prior second generation ARDT
(abiraterone, enzalutamide, darolutamide, or apalutamide).

- First generation androgen receptor inhibitor therapy (e.g. bicalutamide) is allowed
but not considered as prior ARDT therapy.

- Second generation ARDT must be the most recent therapy received. 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 increases in PSA measured at least 1 week
apart. The minimal start value is 2.0 ng/mL 1.0 ng/mL is the minimal starting value
if confirmed rise in PSA is the only indication of progression.

- Soft-tissue progression defined [PCWG3-modified RECIST v1.1 (Eisenhauer et al 2009,
Scher et al 2016)].

- Progression of bone disease: two new lesions only positivity on the bone scan
defines metastatic disease to bone (PCWG3 criteria (Scher et al 2016)).

9a. Participants must have >= 1 metastatic lesion that is present on baseline CT,
MRI, or bone scan imaging obtained prior to randomization.

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.

11. Participants must have adequate organ function:

- Bone marrow reserve:

- ANC >= 1.5 x 109/L

- Platelets >= 100 x 109/L

- Hemoglobin >= 9 g/dL

- Hepatic:

- Total bilirubin < 2 x the institutional upper limit of normal (ULN). For
participants with known Gilbert's Syndrome =< 3 x ULN is permitted.

- ALT or AST =< 3.0 x ULN OR =< 5.0 x ULN for participants with liver metastases.

- Renal:

- eGFR >= 50 mL/min/1.73m2 using the Modification of Diet in Renal Disease (MDRD)
equation.

12. Albumin >= 2.5 g/dL. 13a. Candidates for change in ARDT as assessed by the
treating physician:

- Participants cannot have previously progressed nor had intolerable toxicity to both
enzalutamide and abiraterone.

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. 3a. 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. Prior
treatment with sipuleucel-T is allowed].

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.

6a. Concurrent cytotoxic chemotherapy, immunotherapy, radioligand therapy, PARP
inhibitor, biological 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.

8a. Participants with a history of CNS metastases who 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.

11a. Concurrent serious (as determined by the Principal Investigator) medical
conditions, including, but not limited to New York Heart Association class III or IV
congestive heart failure, 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.

- HIV-infected participants who are at a low risk of AIDS-related outcomes may
participate in this trial.

- Participants with an active documented COVID-19 infection (any grade of disease
severity) at time of informed consent may be included only when completely recovered
(in accordance with local guidance).

12a. Diagnosed with other malignancies that are expected to alter life expectancy or
may interfere with disease assessment. However, participants with a prior history of
malignancy that has been adequately treated and who have been disease free and
treatment free for more than 3 years prior to randomization, are eligible, as are
participants with adequately treated non-melanoma skin cancer and superficial
bladder cancer.

13a. Sexually active males unwilling to use a condom during intercourse while taking
study treatment and for 14 weeks after stopping study treatment. A condom is
required for all sexually active male participants to prevent them from fathering a
child AND to prevent delivery of study treatment via seminal fluid to their partner.

In addition, male participants must not donate sperm for the time period specified above.
If local regulations deviate from the contraception methods listed above to prevent
pregnancy, local regulations apply and will be described in the ICF.

14a. Unmanageable concurrent bladder outflow obstruction or urinary incontinence.

Note: Participant with bladder outflow obstruction or urinary incontinence, which is
manageable and controlled with best available standard of care (incl. pads, drainage) are
all (ICTRP)

nicht verfügbar

Primäre und sekundäre Endpunkte
Radiographic Progression Free Survival (rPFS) (ICTRP)

Overall survival (OS);Radiographic Progression Free Survival 2 (rPFS2);Progression Free survival (PFS) by investigator's assessment;Second Progression Free Survival (PFS2) by investigator's assessment;Biochemical response;Time to First Symptomatic Skeletal Event (TTSE);Time to radiographic soft tissue progression (TTSTP);Time to chemotherapy (TTCT);European Quality of Life (EuroQol) - 5 Domain 5 Level scale (EQ-5D- 5L);Functional Assessment of Cancer Therapy - Prostate (FACT-P) Questionnaire;Brief Pain Inventory - Short Form (BPI-SF) Questionnaire;Number of Participants with Treatment Emergent Adverse Events (ICTRP)

Registrierungsdatum
nicht verfügbar

Einschluss des ersten Teilnehmers
nicht verfügbar

Sekundäre Sponsoren
nicht verfügbar

Weitere Kontakte
Novartis Pharmaceuticals, Novartis Pharmaceuticals (ICTRP)

Sekundäre IDs
2020-003969-19, 2023-507772-50-00, CAAA617B12302 (ICTRP)

Angaben zur Verfügbarkeit von individuellen Teilnehmerdaten
nicht verfügbar

Weitere Informationen zur Studie
https://clinicaltrials.gov/ct2/show/NCT04689828 (ICTRP)