NCT05956639Phase 3Recruiting
The First Affiliated Hospital with Nanjing Medical University · Urology dpt, First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu
Primary Objective:
To explore whether a 6-month course of Rezvilutamide in the triple therapy regimen is non-inferior to long-term Rezvilutamide treatment in improving radiographic progression-free survival (rPFS) in patients with high tumor burden metastatic hormone-sensitive prostate cancer (mHSPC).
Secondary Objectives:
To evaluate and compare the time to prostate-specific antigen (PSA) progression, time to next bone-related event, time to initiation of subsequent anti-prostate cancer treatment, and objective response rate (ORR) between the 6-month and long-term course of Rezvilutamide with androgen deprivation therapy (ADT) plus docetaxel in patients with high tumor burden mHSPC.
To assess and compare the incidence of adverse events between the 6-month and long-term course of Rezvilutamide with ADT plus docetaxel in patients with high tumor burden mHSPC.
Exploratory Objectives:
To observe the circulating tumor cell status at 6 months, 12 months, 18 months, and 24 months in patients with high tumor burden mHSPC receiving the triple therapy regimen.
Eligibility: 18 Years to · Male · * Inclusion criteria:
1. Age ≥ 18 years, male.
2. Eastern Cooperative Oncology Group (ECOG) performance status score of 0-1.
3. Histologically or cytologically confirmed prostate adenocarcinoma without evidence of neuroendocrine or small cell features.
4. High tumor burden, defined as having at least one of the following conditions: 1) Bone scan showing ≥4 bone metastatic lesions (with at least one site outside the pelvis or spine). 2) CT/MRI revealing visceral metastatic lesions (excluding lymph nodes).
5. Planned to receive or maintain androgen deprivation therapy (ADT) during the study period, either by continuous LHRHa treatment or previous bilateral orchiectomy (surgical castration), concurrently with 6 cycles of docetaxel chemotherapy.
6. Organ function levels must meet the following requirements:
* Absolute neutrophil count (ANC) ≥ 1.5 × 10\^9/L.
* Platelets (PLT) ≥ 100 × 10\^9/L.
* Hemoglobin (Hb) ≥ 90 g/L.
* Total bilirubin (TBIL) ≤ 1.5 × upper limit of normal (ULN).
* Alanine aminotransferase (ALT) ≤ 2.5 × ULN.
* Aspartate aminotransferase (AST) ≤ 2.5 × ULN.
* Blood urea nitrogen (BUN) (or urea) and creatinine (Cr) ≤ 1.5 × ULN.
* Left ventricular ejection fraction (LVEF) ≥ 50%.
7. Judged by the investigator to be able to comply with the trial protocol.
8. Voluntarily participate in the clinical trial, understand the study procedures, and have signed the informed consent form.
NCT07316686Phase 1Recruiting
Instituto do Cancer do Estado de São Paulo · Instituto do Câncer do Estado de São Paulo - ICESP, São Paulo
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.
Eligibility: 18 Years to · Male · 1. Men aged 18 years or older.
2. Histological or cytological diagnosis of prostate adenocarcinoma. The presence of intraductal or cribriform carcinoma will be allowed.
3. Presence of metastatic disease on conventional imaging exams (bone scintigraphy and/or CT scan or MRI).
4. 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:
5. PSA ≥2.0 ng/mL with at least two consecutive PSA rises at intervals of at least 1 week.
6. Radiologic progression defined by the investigator.
7. Clinical progression defined by the investigator.
8. Performance status per the Eastern Cooperative Oncology Group (ECOG) equal to 0 or 1.
9. Willingness to continue ongoing ADT.
10. 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
11. 68Ga-PSMA-PET/CT performed during the screening phase showing metastatic (extraprosthetic and extrapelvic) disease with radiotracer uptake and:
12. SUVmax ≥20 in at least one site;
13. SUVmax \>10 in all other measurable metastatic sites.
14. Lesions with uptake at least 1.5 times greater than hepatic background will be considered measurable.
NCT06600802NARecruiting
Centre Jean Perrin · Centre Jean PERRIN, Clermont-Ferrand
Prostate cancer is the most common cancer in men. Its incidence is rising as the population ages. In the localized stage, the 5-year overall survival rate (OS) is 98%. Metastatic progression and resistance to castration have a negative impact on prognosis. Despite recent advances in management, the 5-year OS is around 30%. Therapeutic advances in this indication have been made mainly by the use of taxanes and second-generation hormone therapy. These treatments have improved OS and progression-free survival (PFS). They are now used as standard therapy.
More recently, the Phase III VISION trial confirmed the improvement in OS and radiological PFS achieved by treatment with the radioligand 177Lutetium-PSMA-617 (Lu-PSMA) in patients with advanced metastatic castration-resistant prostate cancer (mCRPC).
This treatment is currently available in early access in France. Despite encouraging results, 40% of patients will not respond to Lu-PSMA, and there are currently no validated predictive factors. Studies are currently on going, but the identification of biomarkers seems necessary to better stratify risk in these patients.
Numerous tissue prognostic tests based on molecular characteristics or cell proliferation are emerging with this in mind. At present, molecular profiling is not a routine technique for prostate cancer, as it is for other solid cancers. At an early stage, the Decipher® Genomic classification tool has shown prognostic utility independently of therapeutic and clinico-pathological data.
According to recent studies, methylome analysis would enable the subdivision of mCRPCs and could help identify new therapeutic targets.
In the metastatic phase, certain molecular abnormalities involving DNA repair genes are predictive of response to PARP inhibitors.
Molecular analysis (mutations, copy number alterations, gene expression, DNA methylation) could therefore be useful in optimizing the management of mCRPC patients treated with Lu-PSMA.
If reliable molecular abnormalities are identified on tissue, a diagnostic technique based on circulating tumor DNA (ctDNA) analysis will be useful in decision-making for these patients. A biological collection will therefore be created during the course of this study, with a view to using ctDNA analysis in subsequent research.
Eligibility: 18 Years to · Male · Inclusion Criteria:
* Male \>18 years of age
* ECOG ≤ 2
* Patient with histologically confirmed of metastatic castration resistant prostatic adenocarcinoma and with tumor biological material available (prostatic biopsies or prostatectomy)
* Patient who received at least one taxane line and a second generation hormone therapy line
* Patient receiving androgen deprivation therapy with serum testosterone \< 50 ng/dL or \< 1.7 nmol/L or having undergone surgical castration
* Progressive mCRPC based based on at least 1 of the following criteria :
* Serum or plasma PSA progression defined as 2 consecutive increases in PSA measured at least 1 week prior. The minimal start value is 2.0 ng/mL ; 1,0 ng/mL is the minimal start value if confirmed increase in PSA is the only indication of progress
* Soft-tissue progression by RECIST 1.1 criteria
* Progression of bone disease : two new lesions ; only the positivity of bone scan defines metastatic bone disease, according to PCWG3 criteria.
* Patients with at least one metastasis, bone and/or soft tissue and/or visceral, documented by the following methods in the 43 days prior to inclusion :
* Bone metastasis (regardless of location) highlighted by bone scan AND/OR
* Lymph nodes metastasis, regardless of size and location; if the metastasis are only lymph nodes, the short axis of at least one node should be at least 15 mm AND outside the pelvis ; AND/OR
* Visceral metastasis, regardless of size and location; a history of visceral metastasis at any time prior to randomization should be encoded as the presence of visceral metastasis at baseline (i.e., a patient with visceral metastasis prior ADT introduction which are disappeared at baseline will be counted as having visceral metastasis and will be considered to have a high tumor volume during stratification)
* Patient with Lu-PSMA treatment indication, confirmed by PET 68Ga-PSMA-11. Eligibility for 68Ga-PSMA-11 PET is defined as:
* At least one lesion with a binding intensity greater than that of the liver parenchyma (definition of positivity),
* All lymph node lesions larger than 25 mm in the short axis must be positive on PSMA PET
* All bone metastases with a soft tissue component ≥ 10 mm in the largest diameter must be positive on PSMA-PET
* All solid organ metastases (e.g., lung, liver, adrenal glands, etc.) ≥ 10 mm in the largest diameter must be positive on PSMA-PET.
* Adequate organ function :
* Bone marrow reserve :
* Absolute neutrophil count ≥ 1.5 x 10\^9/L
* Platelets ≥ 100 x 10\^9/L.
* Hemoglobin ≥ 9 g/dL
* Hepatic function :
* Total bilirubin ≤ 2 x the upper limit of normal (ULN). For participants with known Gilbert's Syndrome ≤ 3 x ULN is permitted.
* Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 3.0 x ULN OR ≤ 5.0 x ULN for patients with liver metastases.
* Albumin \> 2.5 g/dL
* Renal function : Glomerular Filtration Rate (GFR) ≥ 50 mL/min/1.73m2 according to MDRD equation.
* Obtaining the patient's free and informed consent
* Social security scheme or beneficiary.
Exclusion Criteria :
* Continuation of second-generation hormone therapy Patient
* Other cancer in the last 3 years likely to change life expectancy or interfere with the assessment of the disease
* Protected adult
* History of somatic or psychiatric illness/condition that may interfere with study objectives and evaluations
* Patient unable to understand and comply with study instructions and requirements
* ECOG \> 2
* Dilation of pyelocalicial cavities not previously supported
* Obstruction of bladder discharge or uncontrollable and simultaneous urinary incontinence
* Symptomatic spinal cord compression or clinical or radiological findings indicating imminent spinal cord compression
* Fractured risk of bone damage
* Active and symptomatic brain injury
* Concurrent participation in a therapeutic trial and administration of any investigational agent within 28 days of inclusion
* Metastat
NCT06893783Phase 2Recruiting
Inkeun Park · Asan Medical Center, Seoul
This is a phase 2 single-arm, open-label clinical trial designed to evaluate the efficacy and safety of tarlatamab in patients with relapsed extrapulmonary neuroendocrine carcinoma (EPNEC) who have previously received platinum-based first-line chemotherapy. Participants will receive tarlatamab on Cycle 1 Day 1 (C1D1), Day 8 (C1D8), and Day 15 (C1D15), followed by administration every two weeks thereafter. No placebo control is included in this study.
Eligibility: 19 Years to · All · \- Subject has provided informed consent prior to initiation of any study specific activities/procedures.
* Age ≥19 years at the time of signing the informed consent.
* Histologically confirmed relapsed/refractory extra-pulmonary neuroendocrine carcinoma. Neuroendocrine carcinoma includes small cell carcinoma, large cell carcinoma, and mixed histology of neuroendocrine and other histology (e.g., adenoneuroendocrine carcinoma, urothelial carcinoma with neuroendocrine component). In patients with prostate cancer, treatment-emergent neuroendocrine carcinoma (initially adenocarcinoma, but transdifferentiate into neuroendocrine carcinoma after androgen deprivation therapy) will be permitted.
* Cohort 1 (gastrointestinal and pancreaticobiliary cohort): cancers originated from stomach, esophagus, small intestine, colorectal, pancreas, or bile ducts.
* Cohort 2 (genitourinary cohort): cancers originated from prostate, bladder, ureter, urethra, or kidney.
* Subject has progressed or recurred following 1 platinum-based regimen:
* documented first disease progression must be during or following first-line platinum-based systemic chemotherapy. For patients with prostate cancer, especially in cases with treatment-emergent neuroendocrine carcinoma, platinum-based chemotherapy will not need to be the first line therapy.
* patients who received treatment for localized disease who recur are eligible
* patients who received adjuvant Platinum-Etoposide (EP) after resection of their primary tumor who recur are eligible
* Measurable disease as defined per RECIST 1.1 within the 21-day screening period.
• Screening scans performed as SOC(Standard of Care) and prior to informed consent, may be used to confirm subject eligibility if completed within the 21-day screening period, provided that informed consent for the use of these scans is obtained prior to any transfer of data.
* In patients with prostate cancer, patients without RECIST-defined measurable lesion can be included, if disease can be evaluated with Prostate Cancer Working Group(PCWG)-3 criteria.
* Eastern Cooperative Oncology Group (ECOG) PS(Performance Status) of 0 - 2.
* Minimum life expectancy of 12 weeks.
* Adequate organ function, defined as follows:
• Hematological function: Absolute neutrophil count ≥ 1.5 x 10\^9 /L Platelet count ≥ 100 x 10\^9/L Hemoglobin \> 9 g/dL (90 g/L)
• Coagulation function: Prothrombin Time (PT)/International Normalized Ratio (INR) and Partial Thromboplastin Time (PTT) or activated Partial Thromboplastin Time (APTT) ≤ 1.5 x institutional upper limit of normal (ULN) except for subjects undergoing new class anticoagulant therapy (eg, Edoxaban), stable dose for 2 weeks required prior to enrollment.
• Renal function: estimated glomerular filtration rate (eGFR) based on Modification of Diet in Renal Disease (MDRD) calculation ≥ 30 mL/min/1.73 m\^2 or creatinine clearance ≥ 30 mL/min as determined by Cockcroft-Gault equation (Cockcroft and Gault 1976)
• Hepatic function: aspartate aminotransferase (AST) and alanine aminotransferase (ALT) \< 3 x ULN (or \<5 x ULN for subjects with liver involvement) total bilirubin (TBL) \<1.5 x ULN (\<2 x ULN for subjects with liver involvement) (except participants with Gilbert syndrome who must have total bilirubin \<3.0 mg/dL)
• Pulmonary function: no clinically significant pleural effusion. Pleural effusion managed with indwelling pleural catheter (eg, PleurX) are allowed baseline oxygen saturation \>90% on room air
• Cardiac function: cardiac ejection fraction ≥50%, no clinically significant pericardial effusion as determined by an echocardiogram (ECHO) or multigated acquisition (MUGA) scan, and no clinically significant electrocardiogram (ECG) findings Provision of evaluable tumor samples for central testing (archival or in-study biopsy)
NCT06066437Phase 1, Phase 2Recruiting
M.D. Anderson Cancer Center · M D Anderson Cancer Center, Houston, Texas
To learn if the proposed dose of 177Lu rhPSMA-10.1 is safe. Phase 2 will open if the Phase 1 dose is found to be safe.
To learn about the safety and effects of 177Lu rhPSMA-10.1 alone and with androgen deprivation therapy (ADT) on patients with high-risk, localized prostate cancer before they have surgery to remove the disease.
Eligibility: 18 Years to · All · 1. Men ≥18 years of age
2. Histologically documented prostatic adenocarcinoma with an NCCN risk group of high-risk or very high-risk. NCCN High Risk and Very High-Risk criteria shown below. (Network, N.C.C. (2021).
Prostate Cancer (Version 02.2021).
High Risk:
* Has no very-high-risk features and has exactly one high-risk feature:
* cT3a
* Grade Group 4 or Grade Group 5
* PSA \>20 ng/mL
Very high:
* Has at least one of the following:
* cT3b-cT4
* Primary Gleason pattern 5
* 2 or 3 high-risk features
* \>4 cores with Grade Group 4 or 5
3. Prostate biopsy within 90 days prior to randomization is allowed for entry requirements. Prostate biopsy must be reviewed at MD Anderson Cancer Center. Patients with small cell, neuroendocrine, or transitional cell carcinomas are not eligible
4. ECOG performance status (PS) grade 1
5. No evidence of metastatic disease or clinically positive lymph nodes as documented by technetium99m (99mTc) bone scan and by computed tomography (CT) or magnetic resonance imaging (MRI) scans. Imaging may be obtained up to 60 days prior to randomization
6. Minimum prostate tumor volume of 1.5 cm3 or greater as measured on prostate MRI within 60 days prior to randomization
7. Distant metastatic disease or clinically positive lymph nodes not identified by conventional imaging including by technetium-99m (99mTc) bone scan and by computed tomography (CT) or magnetic resonance imaging (MRI) scans but identified PSMA PET is allowed based on provider discretion
8. PSMA expression within the primary tumor with a minimum SUVmax of the primary tumor of at least 8
9. Localized or locally advanced disease deemed by the surgeon to be resectable. Patients must be appropriate candidates for and plan to undergo radical prostatectomy and pelvic lymph node dissection
10. No prior treatment for prostate cancer including prior surgery (excluding transurethral resection of the prostate \[TURP\]), cryoablation, pelvic lymph node dissection, radiation therapy, hormonal therapy or chemotherapy
11. Adequate bone marrow function documented by:
* Hemoglobin ≥11 g/dL
* Absolute neutrophil count ≥1.5 x 109/L
* Platelet count ≥150 x 109/L
12. Adequate renal function defined as creatinine \<1.5 x ULN or estimated glomerular filtration rate \>60 mL/min/1.73 m2 using BSA with CKD-EPI
13. Adequate hepatic function documented by:
* Total bilirubin ≤1.5 x ULN
* AST ≤2.5 x ULN
* ALT ≤2.5 x ULN
* Alkaline Phosphatase (ALP) ≤2.5 x ULN
Patients with Gilbert's syndrome do not need to meet total bilirubin requirements provided their total bilirubin is not greater than their historical level. Gilbert's syndrome must be documented appropriately as past medical history
14. Consents to providing whole blood samples for correlative PSMA evaluation of circulating tumor cells and extra cellular vesicles
15. Willing and able to comply with clinic visits and study-related procedures
16. Provide informed consent signed by study patient
17. To avoid risk of drug exposure through the ejaculate (even men with vasectomies), subjects must use a condom during sexual activity while on study drug and for 6 months following the last dose of study drug. If the subject is engaged in sexual activity with a woman of childbearing potential, a condom is required along with another effective contraceptive method consistent with local regulations regarding the use of birth control methods for subjects participating in clinical studies and their partners. Donation of sperm is not allowed while on study drug and for 3 months following the last dose of study drug.
NCT07474142Phase IIRecruiting
Xijing Hospital · The First Hospital of Lanzhou University, Lanzhou, Gansu
Brief Summary： Under the support of the PROMISE scoring criteria, PSMA PET has demonstrated significant prognostic value. However, previous studies on PSMA PET included patients with various stages of prostate cancer, and the mixture of different disease stages may compromise the accuracy of prognostic tools. This study aims to specifically investigate the prognostic value of initial staging PSMA PET for progression-free survival in patients with newly diagnosed, treatment-naïve prostate cancer, and to develop corresponding prognostic tools.
Need:
The prognostic value of initial staging with PSMA PET is needed for treatment management and study design.
Primary Outcome:
To assess the prognostic value of initial staging by PSMA PET: generate a prognostic tool (PSMA-VISION score) based on initial staging of PSMA PET to predict progression-free survival.
Secondary Outcomes:
To compare PSMA-VISION score with the other prognostic tools (such as NCCN, STARCAP, PPP nomogram, PPP2 nomogram, etc.) and to evaluate the prognostic value of initial staging by PSMA PET to predict overall survival (OS). The correlation with clinicopathological variables and prediction of early progression (Exploratory) was also investigated.
Inclusion:
1. Patients with pathologically confirmed prostate cancer by prostate biopsy.
2. Undergone PSMA PET examination as initial staging before any treatment.
3. Have at least 2 years of follow-up data for progression-free survival and overall survival.
Exclusion Criteria:
1. Patients undergone any prior prostate cancer treatment before undergoing PSMA PET imaging.
2. Patients with metastasized or disseminated malignancy other than prostate cancer
3. Patients with neuroendocrine prostate cancer.
Eligibility: 18 Years to 100 Years · Male · 1. Patients with pathologically confirmed prostate cancer by prostate biopsy.
2. Undergone PSMA PET examination as initial staging before any treatment.
3. Have at least 2 years of follow-up data for progression-free survival and overall survival.
