Clinical trial NCT03454750: Radiometabolic Therapy (RMT) With 177Lu PSMA 617 in Advanced Castration Resistant Prostate Cancer (CRPC)
Official title: Radiometabolic Therapy (RMT) With 177Lu PSMA 617 in Advanced Castration Resistant Prostate Cancer (CRPC): Efficacy and Toxicity Evaluation
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Metastatic Castration Resistant Prostate Cancer
68Ga-PSMA PET/CT Positive
Keywords: Metastatic castration resistant prostate cancer
68Ga-PSMA PET/CT positive
Lead sponsor: Istituto Romagnolo per lo Studio dei Tumori Dino Amadori IRST S.r.l. IRCCS
Sponsor class: OTHER
First posted: 2018-03-06
Enrollment: 143
Sex: MALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: Radiometabolic Therapy (RMT) with 177Lu PSMA 617 in advanced castration resistant prostate cancer (CRPC): efficacy and toxicity evaluation

Detailed description: Radiometabolic Therapy (RMT) with 177Lu PSMA 617 in advanced castration resistant prostate cancer (CRPC): efficacy and toxicity evaluation. Single-center, prospective, non controlled, open label, phase II trial. The main objective of this study is to evaluate the Disease Control Rate (DCR) and the safety as co-primary objective.

The secondary objectives are: late toxicity, PFS, OS, biochemical response and dosimetry.

Eligibility criteria: Inclusion Criteria:

1. Male, Age \> 18 years.
2. Patients must have histologically or cytologically confirmation of advanced prostate cancer castration resistant defined according to PCWG3 criteria
3. Measurable disease according to RECIST 1.1. criteria; also patients with bone lesions only could be enrolled
4. Patients with documented disease will be admitted to therapeutic phase only if the diagnostic PET/CT 68Ga-PSMA images demonstrate a significant uptake (tumor to background ratio \>2.5) at metastatic tumour site (or in the primary when present, or both)
5. Patients with documented radiological progression (in soft tissue and / or bone) and / or biochemical progression (sequence of 3 PSA rising values from a screening PSA value ≥ 2 ng / ml) according to PCWG3 in pre-study period, refractory or unfit to conventional standard treatments (hormonal or chemotherapeutic treatment such as abiraterone, enzalutamide and docetaxel)
6. Concomitant LHRH analogs assumption is allowed
7. Life expectancy greater than 6 months.
8. ECOG performance status \<2
9. Adequate haematological, liver and renal function: haemoglobin \>= 9 g/dL, absolute neutrophil count (ANC) \>= 1.5 x 109 /L, platelets \>= 100 x 109 /L, bilirubin ≤1.5 X upper normal limit (UNL), alanine aminotransferase (ALT) and Aspartate aminotransferase (AST) \<2.5 X UNL (\< 5 X UNL in presence of liver metastases, creatinine \< 2 mg/dL).
10. Participant is willing and able to give informed consent for participation in the study
11. Other known malignant neoplastic diseases in the patient's medical history with a disease-free interval of less than 3 years (except for previously treated basal cell carcinoma).

Exclusion Criteria:

1. Patients treated with chemotherapy and 223Ra radiotherapy within 4 weeks and treated within 2 weeks with palliative radiotherapy.
2. All acute toxic effects of any prior therapy (including surgery, radiation therapy, chemotherapy) must have resolved to a grade ≤ 1 according to National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.03 (CTCAE)
3. ECOG performance status \>2
4. Participation in another clinical trial with any investigational agents within 30 days prior to study screening.
5. Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
6. Assessed bone marrow invasion \> 50%

Primary outcomes:
measure: Disease Control Rate (DCR )
timeFrame: up to 36 months
measure: Incidence of Treatment-Emergent Adverse Events
timeFrame: up to 30 days after the last treatment cycle
Secondary outcomes:
measure: Progression free survival (PFS)
timeFrame: up to 36 months
measure: Overall survival (OS)
timeFrame: up to 36 months
Other outcomes:
Locations:
city: Meldola
country: Italy
facility: Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST)
state: FC
Study officials:
affiliation: IRST IRCCS
name: Giovanni Paganelli
role: STUDY_CHAIR
References:
citation: De Giorgi U, Sansovini M, Severi S, Nicolini S, Monti M, Gurioli G, Foca F, Casadei C, Conteduca V, Celli M, Di Iorio V, Calistri D, Matteucci F, von Eyben FE, Attard G, Paganelli G. Circulating androgen receptor gene amplification and resistance to 177Lu-PSMA-617 in metastatic castration-resistant prostate cancer: results of a Phase 2 trial. Br J Cancer. 2021 Oct;125(9):1226-1232. doi: 10.1038/s41416-021-01508-5. Epub 2021 Jul 31.
citation: Paganelli G, Sarnelli A, Severi S, Sansovini M, Belli ML, Monti M, Foca F, Celli M, Nicolini S, Tardelli E, Marini I, Matteucci F, Giganti M, Di Iorio V, De Giorgi U. Dosimetry and safety of 177Lu PSMA-617 along with polyglutamate parotid gland protector: preliminary results in metastatic castration-resistant prostate cancer patients. Eur J Nucl Med Mol Imaging. 2020 Dec;47(13):3008-3017. doi: 10.1007/s00259-020-04856-1. Epub 2020 May 20.