Pilot study on tumor absorbed dose dynamics and pre-treatment dosimetry with [177Lu]-PSMA-I&T in metastatic castration-resistant prostate cancer

Prior treatment

• Previous PSMA-targeted radioligand therapy
• Previous treatment with radium-223 or external irradiation within 3 months prior to inclusion
• Any investigational agent within 28 days or 5 half-lives, whichever is longer, prior to the day of inclusion.

Other illness

• Other malignancies that are expected to alter life expectancy or may interfere with disease assessment
• Known hypersensitivity to the PSMA-radioligand

Lab values

• Concurrent serious medical conditions, as determined by the treating physician, including, but not limited to, New York Heart Association class III or IV congestive heart failure, history of congenital prolonged QT syndrome, uncontrolled infection or other significant co-morbid conditions that in the opinion of the Principal Investigator might impair study participation or cooperation

Other

• Transfusion within 60 days of inclusion
• Extensive bone marrow metastases
• Bone metastases with symptomatic cord compression, or clinical or radiologic findings indicative of impending cord compression
• Incontinence

• Patients must have a confirmed diagnosis of mCRPC and have developed mCRPC during treatment with Androgen Deprivation Therapy (ADT) and Androgen Receptor Pathway Inhibitor (ARPI), but without having received docetaxel in the mCRPC phase.
• The included patients must have comparable disease burden, PSMA PET tumor volume, and distribution of metastases, to reduce the tumor sink effect. This will be assessed by using baseline [68Ga]Ga-PSMA PET/CT or PET/MR and PSA, including PSMA-positive tumor volume, number and distribution of metastases, extent of bone involvement, and PSA level. Following enrollment of the first participant, subsequent candidates will be compared with the baseline imaging findings of the first participant. Candidates with markedly different tumor burden or metastatic distribution will not be enrolled.
• Patients must be capable of understanding, signing, and complying with the approved ICF, including adherence to all requirements and restrictions outlined in the ICF and this protocol
• Patients must be ≥18 years of age
• Patients must have an ECOG performance status of ≤ 1
• Patients must have a life expectancy > 12 months
• Patients must have adequate organ function as conformed by the following laboratory tests: Hb ≥13 g/dL, WBC ≥4.0 × 10⁹/L, Neutrophil granulocytes ≥1.6 × 10⁹/L, Platelets ≥150 × 10⁹/L, eGFR ≥50 mL/min, ASAT ≤1.5 × ULN, ALAT ≤1.5 × ULN, ALP: No upper limit. May be increased due to bone metastases, Albumin ≥28 g/L, total bilirubin ≤1.5 × ULN. Patients with Gilbert’s syndrome: ≤40 µmol/L). ULN = upper limit of normal (laboratory reference range)
• Patients must have prior orchiectomy and/or ongoing androgen-deprivation therapy
• Male participants with female partners of reproductive potential must use effective contraception, including adequate barrier protection during the study and for at least 6 months after last [177Lu]Lu-PSMA-I&T administration.
• Patients must be on a stable bisphosphonate or denosumab regimen for ≥30 days prior to inclusion are eligible.
• Baseline [68Ga]Ga-PSMA PET/CT or PET/MR, obtained ≤ 21 days prior to inclusion, must demonstrate PSMA-positive metastatic disease considered suitable for PSMA-targeted radioligand therapy. PSMA positivity is defined as tracer uptake greater than that in normal liver in more than 50% of metastatic lesions. Patients must have 5-20 metastatic lesions (lymph nodes and bone, no metastases to other organs).
• At least 2 lesions must be suitable for tumor dosimetry, (preferably ≥ 2-3 cm in diameter, isolated, and within 30 cm apart to allow single bed SPECT imaging)
• It must be assumed that the patient will be able to complete the protocol defined treatment of six [177Lu]Lu-PSMA cycles.