Phase I Study of Docetaxel and 177-Lutetium-PSMA-I&T in First-Line Treatment for Patients With Metastatic Castration-Resistant Prostate Adenocarcinoma
About this study
This is a Phase I, open-label, single-center study evaluating the safety, tolerability, and recommended Phase II dose of docetaxel when combined with a fixed dose of 177-Lutetium-PSMA-I\&T in chemotherapy-naïve patients with metastatic castration-resistant prostate cancer (mCRPC). Patients will receive standard androgen deprivation therapy, docetaxel at escalating doses (50 mg/m², 60 mg/m², 75 mg/m² every 3 weeks), and 177Lu-PSMA-I\&T at a fixed dose of 7.4 GBq every 6 weeks (up to 4 cycles). A 3+3 dose escalation design will be employed. Secondary endpoints include safety profile, treatment-limiting toxicities, treatment completion rate, and delayed toxicity. Exploratory endpoints include PSA response, radiographic progression-free survival (rPFS), and PERCIST-based response rate.
- Condition
- Prostate Cancer (Adenocarcinoma)
- Tested
- Docetaxel 50mg/m2, Docetaxel 60mg/m2, Docetaxel 75 mg/m², 177Lu-PSMA-I&T
- Sponsor
- Instituto do Cancer do Estado de São Paulo
Who can join
- Age
- 18 years and older
- Sex
- Male only
- Healthy volunteers
- Not accepted
Inclusion 26
- Minimum age: 18 years
- Eligible sex: Male
- Study condition: Prostate Cancer (Adenocarcinoma)
- Men aged 18 years or older.
- Histological or cytological diagnosis of prostate adenocarcinoma. The presence of intraductal or cribriform carcinoma will be allowed.
- Presence of metastatic disease on conventional imaging exams (bone scintigraphy and/or CT scan or MRI).
- Patients with castration-resistant disease, defined as testosterone \<50 ng/mL in the context of prior orchiectomy or ongoing androgen deprivation therapy (ADT) with LHRH agonists or antagonists, plus at least one of the criteria below:
- PSA ≥2.0 ng/mL with at least two consecutive PSA rises at intervals of at least 1 week.
- Radiologic progression defined by the investigator.
- Clinical progression defined by the investigator.
- Performance status per the Eastern Cooperative Oncology Group (ECOG) equal to 0 or 1.
- Willingness to continue ongoing ADT.
- Adequate organ function as defined below:
- Parameter Requirement
- Neutrophils ≥ 1,500/µL
- Hemoglobin ≥ 12 g/dL
- Platelets ≥ 100,000/µL
- Creatinine ≤ 1.5 x upper limit of normal
- Potassium \> 3.5 mmol/L and \<5.0 mmol/L
- Total Bilirubin ≤ ULN (unless Gilbert's disease)
- AST (TGO) ≤ 2.5 x ULN
- ALT (TGP) ≤ 2.5 x ULN
- 68Ga-PSMA-PET/CT performed during the screening phase showing metastatic (extraprosthetic and extrapelvic) disease with radiotracer uptake and:
- SUVmax ≥20 in at least one site;
- SUVmax \>10 in all other measurable metastatic sites.
- Lesions with uptake at least 1.5 times greater than hepatic background will be considered measurable.
Exclusion 6
- Presence of any small-cell or neuroendocrine component of prostate carcinoma.
- Prior receipt of chemotherapy or radiopharmaceuticals in the castration-resistant setting.
- Presence of another active malignancy requiring treatment or a cancer diagnosis within the past 5 years. Carcinoma in situ of any site, squamous cell carcinoma of the skin, basal cell carcinoma of the skin, or papillary bladder tumors will be allowed if previously treated.
- Severe urinary incontinence at the investigator's discretion.
- 18F-FDG-PET/CT will be performed during screening and will be considered exclusionary if there is discordance with the 68Ga-PSMA-PET/CT. Discordance is defined as FDG-hypermetabolic lesions with absent or low PSMA uptake (SUVmax \<10) in more than 50% of measurable metastatic lesions.
- Patients with brain metastases visible on 68Ga-PSMA-PET/CT.
Where
1 site, 1 recruiting
Instituto do Câncer do Estado de São Paulo - ICESP
São Paulo, Brazil
Contact
-
Research Center, Assistant
+55 11 3893-3566 icesp.pesqclinica@hc.fm.usp.br
Potential match only. Final eligibility is determined by the study team.