NCT04595929NARecruiting
St. Petersburg State Pavlov Medical University · First Pavlov State Medical University of St. Petersburg, Saint Petersburg
Stomach cancer is recognized as the third leading cause of death of cancer patients worldwide. Despite the radical treatment carried out, the progression of gastric cancer occurs in 30-40% of patients. The most common type of tumor progression of this localization is peritoneal carcinomatosis. When peritoneal carcinomatosis occurs, the median survival of patients does not exceed 3 months, the overall survival is no more than 6 months. Unfortunately, when peritoneal carcinomatosis occurs, palliative chemotherapy remains the only treatment option. The modern strategy for the prevention and treatment of peritoneal carcinomatosis is based on the concept of regional chemotherapy. The main methods of regional chemotherapy are hyperthermic intraperitoneal chemotherapy (HIPEC) and Pressured Intraperitoneal Aerosol Chemotherapy (PIPAC). PIPAC is a new technology for delivering chemotherapy drugs to tumor nodes on the surface of the peritoneum and allows the cytostatic to be evenly distributed over the abdominal cavity, increasing the depth of its penetration into tumor nodes due to the properties of aerosol and gradients of intra-abdominal and interstitial pressure. The method has a number of advantages over the HIPEC method: a large penetration depth of drugs, low trauma, the possibility of repeated use. We offer PIPAC for patients with locally advanced gastric cancer and a high risk of developing peritoneal carcinomatosis in an adjuvant mode in addition to standard treatment to prevent the development of carcinomatosis.
Eligibility: 18 Years to 65 Years · All · * Histologically confirmed, medically operable, resectable stomach adenocarcinoma (cT3-4, any N category, M0).
* No preceding cytotoxic or targeted therapy.
* No prior partial or complete tumor resection.
* Female and male patient ≥ 18 and ≤ 75 years. Female patient with childbearing potential needs to have a negative pregnancy test within 7 days prior to study start. Males and females of reproductive potential must agree to practice highly effective contraceptive measures\* during the study. Male patients must also agree to refrain from father a child during treatment and additionally to use a condom during treatment period. Their female partner of childbearing potential must also agree to use an adequate contraceptive measure.
\*highly effective (i.e. failure rate of \<1% per year when used consistently and correctly) methods: intravaginal and transdermal combined (estrogen and progestogen containing) hormonal contraception; injectable and implantable progestogen-only hormonal contraception; intrauterine device (IUD); intrauterine hormone-releasing system (IUS); bilateral tubal occlusion; vasectomised partner; sexual abstinence (complete abstinence is defined as refraining from heterosexual intercourse during the entire period of risk associated with the study treatments).
* ECOG = 0-2.
* Exclusion of distant metastases by CT or MRI of abdomen, pelvis, and thorax, bone scan or MRI (if bone metastases are suspected due to clinical signs). Exclusion of the infiltration of any adjacent organs or structures by CT or MRI.
* Laparoscopic exclusion of peritoneal carcinomatosis at initial staging, before start of FLOT chemotherapy
* Adequate hematological, hepatic and renal function parameters:
Leukocytes ≥ 3000/mm³, platelets ≥ 100,000/mm³, neutrophil count (ANC) ≥1000/µL Serum creatinine ≤ 1.5 x upper limit of normal Bilirubin ≤ 1.5 x upper limit of normal, AST and ALT ≤ 3.0 x upper limit of normal, alkaline phosphatase ≤ 6 x upper limit of normal For patients not receiving therapeutic anticoagulation: INR or aPTT ≤ 1.5 x ULN; for patients receiving therapeutic anticoagulation: stable anticoagulant regimen.
* Patient able and willing to provide written informed consent and to comply with the study protocol and with the planned surgical procedures.
NCT06732856Phase 1, Phase 2Recruiting
Asan Medical Center · Asan Medical Center, Seoul
Claudin 18.2 is a promising therapeutic target overexpressed on the surface of gastric cancer cells. The addition of zolbetuximab, the monoclonal antibody targeting Claudin 18.2 to chemotherapy in two recent Phase 3 studies prolonged survival outcomes, indicating that Claudin 18.2 is a valid target in gastric cancer. Asan Medical Center researchers conducted a study on Claudin 18.2 expression in patients with operable gastric cancer and defined moderate to strong claudin expression in more than 75% of tumor cells as Claudin 18.2 overexpression, which was observed in 46.5% of patients with stage I-III tumors. This suggests that zolbetuximab-based treatment may be possible in patients with LAGC.
Therefore, The investigator designed a prospective, multicenter, open-label, Phase Ib/II study to determine the efficacy and safety of zolbetuximab/DOS as neoadjuvant chemotherapy in patients with LAGC.
Eligibility: 19 Years to · All · 1. Patients with newly diagnosed, pathologically confirmed, potentially resectable gastric or gastroesophageal junction adenocarcinoma
2. Subjects who are CLDN18.2 positive (VENTANA 43-14A ≥75%)
3. Patients with clinical stage T3-4/N0 or T2-4/N+ on CT according to the American Joint Committee on Cancer (AJCC) 8th edition
4. If suspected by CT, patient who has not been confirmed to have peritoneal seeding by laparoscopy
5. Subject able to provide signed informed consent form, including compliance with the requirements and contraindications specified in the informed consent form (ICF) and in this protocol
6. Patients aged 19 years or older at study entry
7. Patient with Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1
8. Patient with expected survival \>12 months
9. Weight \>30 kg
10. Patient without neuropathy A. Grade 1 is allowed based on NCI CTCAE v5.0. B. Grade 2 or higher is excluded based on NCI CTCAE v5.0
11. Individual with confirmed adequate normal organ and bone marrow function, as defined in the applicable items below:
* Hemoglobin ≥9.0 g/dL
* Absolute neutrophil count (ANC) \>1.5 x 103/mcL (\>1,500 per mm3)
* Platelet count ≥100 x 109/L
* Serum bilirubin ≤1.5 x institutional upper limit of normal (ULN)
* AST (SGOT)/ALT (SGPT) ≤2.5 x institutional ULN
* Measured creatinine clearance (CL) \>40 mL/min or creatinine CL \>40 mL/min as calculated by Cockcroft-Gault formula (Cockcroft and Gault 1976) or based on a 24-hour urine sample for determination of creatinine clearance
1. Male creatinine CL (mL/min) = Weight (kg) x (140 - Age) / 72 x Serum creatinine (mg/dL)
2. Female creatinine CL (mL/min) = Weight (kg) x (140 - Age) / 72 x Serum creatinine (mg/dL) x 0.85
12. Evidence of menopause, or negative urine/blood pregnancy test in premenopausal women; women with amenorrhea for at least 12 months without any other medical cause are considered menopausal. The following age requirements apply:
* A woman under age 50 is considered menopausal if 1) she has had amenorrhea for at least 12 months without hormone therapy, and 2) her LH and FSH blood levels are at menopausal levels or she has undergone bilateral oophorectomy, hysterectomy, etc.
* A woman aged 50 years or older is considered menopausal if
1. she has had amenorrhea for at least 12 months without hormone therapy, or
2. she became menopause after 1 year of amenorrhea following radiation or anticancer treatment, or
3. she has undergone bilateral oophorectomy, bilateral salpingectomy, hysterectomy, etc.
13. Patient who is willing and able to comply with the protocol during the study, including treatments and tests such as scheduled visits, follow-up, etc.
NCT04895709Phase 1, Phase 2Recruiting
Bristol-Myers Squibb · Community Cancer Institute, Clovis, California
The purpose of this study is to assess the safety, tolerability, and recommended dose(s) of BMS-986340 as monotherapy and in combination with nivolumab, docetaxel, or Pumitamig in participants with advanced solid tumors. This study is a first-in-human (FIH) study of BMS-986340 in participants with advanced solid tumors.
Eligibility: 18 Years to · All · Inclusion Criteria
* Fresh pre-treatment and on-treatment tumor biopsy must be provided for biomarker analysis.
* Measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 and at least 1 lesion accessible for biopsy. Fine needle biopsy, cytology, and bone lesion biopsies are not acceptable.
* Eastern Cooperative Oncology Group Performance Status of 0 or 1.
* Radiographically documented progressive disease on or after the most recent therapy.
* Received standard-of-care therapies, (except for Part 1C, 2C and 2D, where participants with prior docetaxel use for the advanced/metastatic setting will be excluded), including an available programmed death (ligand)-1 inhibitor known to be effective in the tumor type for which they are being evaluated.
* Advanced or metastatic disease and have received, be refractory to, not be a candidate for, or be intolerant of existing therapies known to provide clinical benefit for the condition of the participant.
Exclusion Criteria
* Women who are pregnant or breastfeeding.
* Primary central nervous system (CNS) malignancy.
* Untreated CNS metastases.
* Leptomeningeal metastases.
* Concurrent malignancy requiring treatment or history of prior malignancy active within 2 years prior to the first dose of study treatment.
* Active, known, or suspected autoimmune disease.
* Condition requiring systemic treatment with either corticosteroids within 14 days or other immunosuppressive medications within 30 days of the first dose of study treatment.
* Prior organ or tissue allograft.
* Uncontrolled or significant cardiovascular disease.
* Major surgery within 4 weeks of study drug administration.
* History of or with active interstitial lung disease or pulmonary fibrosis.
* Other protocol-defined inclusion/exclusion criteria apply.
NCT06704191Phase 1, Phase 2Recruiting
Mayo Clinic · Mayo Clinic in Florida, Jacksonville, Florida
This phase Ib/II trial compares the safety, tolerability and acceptability of intravesical chemotherapy given at home to in-clinic administration in patients with non-muscle invasive bladder cancer. Chemotherapy drugs, such as bacillus Calmette-Guerin (BCG), gemcitabine, docetaxel, and mitomycin C, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Standard of care chemotherapy for non-invasive bladder cancer is usually given directly into the bladder through a catheter (intravesical). This process requires numerous visits and can be disruptive to the lives of patients and caregivers. Bringing cancer care to the patients with in-home intravesical therapy may help reduce the disruption to daily lives. In-home intravesical chemotherapy may be safe and tolerable and may also be preferable to in-clinic administration in patients with non-muscle invasive bladder cancer.
Eligibility: 18 Years to · All · * PHASE IB ONLY: Female or male patients with histologically confirmed non-muscle invasive bladder cancer (stage Ta, Tis, or T1) who are currently receiving induction therapy with one of the following eligible intravesical treatment regimens
* Gemcitabine
* Sequential gemcitabine/docetaxel
* Bacillus Calmette-Guerin
* Mitomycin C
* PHASE II ONLY: Female or male patients with histologically confirmed non-muscle invasive bladder cancer (stage Ta, Tis or T1) who are receiving maintenance therapy with an eligible regimen
* PHASE IB ONLY: Able to be successfully catheterized and able to tolerate first dost of intravesical therapy in the outpatient clinic
* Residing within the area serviced by supplier network
* Residence either has Wi-Fi or cellular data network connection for virtual telehealth visits
* Age ≥ 18 years at time of registration
* Signed informed consent form by patient
* Willing and able to comply with the study protocol in the investigator's judgment
* Ability to complete questionnaire(s) by themselves or with assistance
* Willingness to follow birth control requirements for females and males of reproductive potential
NCT06929286Phase 3Recruiting
Memorial Sloan Kettering Cancer Center · Johns Hopkins University (Data Collection Only), Baltimore, Maryland
The purpose of this study is to compare the effectiveness of different FDA-approved/NCCN-recommended drug treatments for NMIBC. In particular, the FDA-approved drug nadofaragene firadenovec will be compared to usual care with other NCCN-recommended standard treatments for NMIBC (gemcitabine with or without docetaxel, mitomycin, re-treatment with BCG, or pembrolizumab).
Eligibility: 21 Years to · All · * 21 years of age or older
* Being treated for high-grade NMIBC (Tis, Ta, or T1) under the care of the participating treating urologists
* One or more prior induction course of BCG at any point in time and judgment by the treating urologist that BCG has failed
°Any amount of maintenance BCG is allowed
* In the previous 12 months, receipt of at least one instillation of any intravesical agent (induction or maintenance) or one administration of systemic therapy for NMIBC treatment
* An intravesical agent can include BCG or any other NMIBC treatment
* Up to 15 months from the last instillation is allowed for the treating physician to perform a transurethral resection of bladder tumor (TURBT) so long as there is evidence/suspicion of recurrent disease (by urinary cytology, imaging, or cystoscopy) within 12 months of last exposure to an intravesical agent.
* In the opinion of the treating urologist, there is no contraindication to treatment with nadofaragene firadenovec (i.e. hypersensitivity to IFNa, severe immunosuppression) and there is uncertainty over whether nadofaragene is better than "best usual care"
NCT07322263Phase 2Recruiting
Michael A. O'Donnell · University of Iowa, Iowa City, Iowa
The goal of this clinical trial is to learn whether a combination of two chemotherapy drugs, Gemcitabine and Docetaxel, can treat high-grade non-muscle-invasive bladder cancer (HG-NMIBC) in adults whose cancer failed conventional BCG therapy. The drugs are given directly into the bladder (intravesically), one immediately after the other.
The study will also assess the safety of this treatment.
The main questions it aims to answer are:
Can this drug combination effectively treat HG-NMIBC that did not respond to BCG and help prevent the cancer from coming back, offering long-term protection? What side effects or medical issues do participants experience during treatment?
Researchers will evaluate this non-surgical approach as a potential alternative to bladder removal surgery (radical cystectomy), with the goal of validating it as a bladder-sparing option in this setting.
Participants will:
* Go through a screening process, including tumor removal and imaging tests
* Receive weekly bladder treatments with Gemcitabine followed by Docetaxel for 6 weeks
* If the cancer responds, continue with similar once monthly treatments (maintenance therapy) for up to 2 years
* Attend regular check-ups, including bladder exams, urine tests, biopsies, and optional quality-of-life surveys
* Possibly receive a second 6-week treatment cycle if the cancer returns early
* Be followed for up to 5 years to monitor long-term outcomes
Eligibility: 18 Years to 99 Years · All · Histologically confirmed diagnosis of urothelial carcinoma of the bladder without synchronous or metachronous upper tract involvement or prostatic urethral involvement. Subjects with negative upper tract imaging within 6 months of the study start and visually normal prostates are potentially eligible. Those with a history of suspicious upper tract cytology or suspicious prostatic urethra visually will require additional upper tract washes and/or biopsies to rule out concurrent extravesical disease.
Eligible bladder cancer presentations include:
* Carcinoma in situ (CIS), with or without non-muscle-invasive stage Ta or T1 tumors of any grade.
* High-Grade Papillary tumors (stages Ta and/or T1) without CIS.
* All visible bladder tumors must be completely resected within 8 weeks prior to initiating intravesical Gem/Doce therapy.
* If more than 8 weeks have passed since diagnosis or resection of index bladder CIS ± non-invasive tumor (pTa or T1 tumors), an office cystoscopy must be performed within 8 weeks of Gem/Doce initiation to confirm no visible tumor regrowth.
BCG-Unresponsive Disease as defined by any of the following FDA-accepted criteria:
* Occurrence of high-grade, stage T1 cancer after at least 5/6 weekly BCG induction treatments.
* Occurrence of CIS within 12 months, or high-grade papillary disease, stage Ta/T1, within 6 months after an "adequate" course of BCG therapy.
An "adequate" course of BCG includes at least 5/6 weekly BCG induction treatments and at least 2/3 weekly BCG maintenance or 2/6 weekly BCG re-induction treatments.
* N.B: Physician may have some flexibility (+/- 1 month) in the use of 6 and 12 months to define BCG-unresponsive NMIBC.
* N.B: Once a patient has been correctly defined as having BCG-unresponsive disease, they will be considered to always be BCG-unresponsive for the purpose of this study. In other words, there is no restriction as to when the BCG-unresponsive term was assigned.
* The occurrence of low-grade (LG) Ta disease will not be considered a HG relapse event given its prognosis is much more favorable that HG disease. However, all LG tumor must be completely resected before continuing with Gemcitabine/Docetaxel therapy.
* Subjects must be eligible for radical cystectomy and decline this standard of care treatment or not be a surgical candidate for radical cystectomy (as appropriate) based on other comorbidities.
* All grossly visible disease in the bladder must be fully resected with pathologic stage and grade assessed at the local study institution. Local pathologists are strongly encouraged to use the current LG and HG AJCC criteria.
NB: For institutions that still use the 3-tiered grading system, Ta Gr1 and Gr 2 will be considered LG while any Ta Gr3 or T1 Gr2 or Gr3 will be considered HG.
* Patients enrolled in other clinical trials must have received their last treatment at least 8 weeks prior to enrollment if the treatment was an intravesical agent. If the treatment included a systemic immune-modulating agent (e.g. anti-PD(L)-1 or anti CTLA4) then at least two dosing intervals must have elapsed untreated before the patient is eligible.
* Age \> 18 and must be able to read, understand and sign the local informed consent.
* Patients must have an Eastern Cooperative Oncology Group (ECOG) performance Status of 2 or less, including patients who are not surgical candidates due to comorbid conditions.
* Women of childbearing potential must have a negative pregnancy test at screening.
* All patients of childbearing potential must be willing to consent to using effective contraception, i.e., IUD, Birth control pills, Depo-Provera, and/or condoms while on treatment and for 3 months after their last Gemcitabine/Docetaxel treatment.
* No intravesical or upper tract topical therapy within 8 weeks of study entry.
* Must be willing and able to comply with all protocol requirements.
* Should have a Complete Blood Count (CBC) with differential before the index tumor resection or bi
NCT06488222Phase 2Recruiting
University of Florida · University of Florida, Gainesville, Florida
Bladder cancer is the 8th most common cancer in the UF Health Cancer Center catchment area and the 7th most common cancer presenting to UFHealth. Most newly diagnosed cases are stage I bladder cancer, which is defined by having no deep muscle invasion and no evidence of disease beyond the bladder. The current use in BCG (Bacillus Calmette-Guerin) refractory disease and the ongoing evaluation in BCG naïve high-risk disease support evaluation of intravesical gemcitabine and docetaxel in decreasing disease recurrence in intermediate risk stage I bladder cancer.
This study will investigate the efficacy and subject compliance with treatment of low grade intermediate risk bladder cancer with intravesical gemcitabine and docetaxel.
Eligibility: 18 Years to · All · * Adults ≥ 18 years of age.
* Low-grade (Ta) Intermediate risk urothelial carcinoma of the bladder (defined as recurrent low-grade Ta, solitary low-grade Ta \> 3 cm, multifocal low-grade Ta). Up to 10% high grade component is allowed.
* ECOG Performance Status of 0-2.
* No evidence of upper tract urothelial carcinoma based on CT, MRI, or retrograde pyelograms.
* No urethral involvement based on cystoscopy.
* No visible disease based on cystoscopy within 60 days of study enrollment.
* Neutrophil counts ≥ 1500 cells/mm3
* Platelet counts \>100,000 cells/mm3
* Subjects with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen \[as determined by the treating physician or approved by the PI\] may be included.
* Subjects of childbearing potential (SOCBP) must be using an adequate method of contraception to avoid pregnancy throughout the study and for at least 6 months after the last dose of study drug to minimize the risk of pregnancy. Prior to study enrollment, subjects of childbearing potential must be advised of the importance of avoiding pregnancy during trial participation and the potential risk factors for an unintentional pregnancy.
* Subjects with partners of child-bearing potential must agree to use physician-approved contraceptive methods (e.g., abstinence, condoms, vasectomy) throughout the study and should avoid conceiving children for 3 months following the last dose of study drug.
* Written informed consent obtained from the subject and the subject agrees to comply with all the study-related procedures.
NCT04895709Phase 1, Phase 2Recruiting
Bristol-Myers Squibb · Community Cancer Institute, Clovis, California
The purpose of this study is to assess the safety, tolerability, and recommended dose(s) of BMS-986340 as monotherapy and in combination with nivolumab, docetaxel, or Pumitamig in participants with advanced solid tumors. This study is a first-in-human (FIH) study of BMS-986340 in participants with advanced solid tumors.
Eligibility: 18 Years to · All · Inclusion Criteria
* Fresh pre-treatment and on-treatment tumor biopsy must be provided for biomarker analysis.
* Measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 and at least 1 lesion accessible for biopsy. Fine needle biopsy, cytology, and bone lesion biopsies are not acceptable.
* Eastern Cooperative Oncology Group Performance Status of 0 or 1.
* Radiographically documented progressive disease on or after the most recent therapy.
* Received standard-of-care therapies, (except for Part 1C, 2C and 2D, where participants with prior docetaxel use for the advanced/metastatic setting will be excluded), including an available programmed death (ligand)-1 inhibitor known to be effective in the tumor type for which they are being evaluated.
* Advanced or metastatic disease and have received, be refractory to, not be a candidate for, or be intolerant of existing therapies known to provide clinical benefit for the condition of the participant.
Exclusion Criteria
* Women who are pregnant or breastfeeding.
* Primary central nervous system (CNS) malignancy.
* Untreated CNS metastases.
* Leptomeningeal metastases.
* Concurrent malignancy requiring treatment or history of prior malignancy active within 2 years prior to the first dose of study treatment.
* Active, known, or suspected autoimmune disease.
* Condition requiring systemic treatment with either corticosteroids within 14 days or other immunosuppressive medications within 30 days of the first dose of study treatment.
* Prior organ or tissue allograft.
* Uncontrolled or significant cardiovascular disease.
* Major surgery within 4 weeks of study drug administration.
* History of or with active interstitial lung disease or pulmonary fibrosis.
* Other protocol-defined inclusion/exclusion criteria apply.
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.
