NCT05278208Phase 1, Phase 2Recruiting
Nationwide Children's Hospital · Children's Hospital Colorado, Aurora, Colorado
This study will evaluate the safety and efficacy of Lutathera (177Lu-DOTATATE) in patients with progressive or recurrent High-Grade Central Nervous System (CNS) tumors and meningiomas that demonstrate uptake on DOTATATE PET. The drug will be given intravenously once every 8 weeks for a total of up to 4 doses over 8 months in patients aged 4 to \<12 years (Phase I) or 12 to \</=39 years (Phase II) to test its safety and efficacy, respectively.
Funding Source - FDA OOPD (grant number FD-R-0532-01)
Eligibility: 4 Years to 39 Years · All · All participants must meet the following inclusion and exclusion criteria. No exceptions will be given. Imaging studies to establish eligibility must be done within three weeks prior to enrollment. All other clinical evaluations to establish eligibility (except for \[68Ga\]Ga-DOTATATE PET) must be done within 7 days prior to enrollment.
1. Screening Criteria
1.1 Diagnosis Patient must have a diagnosis of primary high-grade CNS tumor (any histopathologic diagnosis that is WHO grade III-IV) or meningioma (any histologic grade) that is recurrent, progressive, or refractory. Note that patients with DIPG (based on radiographic/clinical diagnosis) who have undergone biopsy will be eligible with histologic diagnosis of grade II-IV infiltrating glioma. All tumors must have histologic verification either at the time of diagnosis or recurrence, except for patients meningioma who have not previously undergone biopsy or resection.
Note: Refractory disease is defined as the presence of persistent abnormality on conventional MRI that is further distinguished by histology (biopsy or sample of lesion) or advanced imaging, OR as determined by the treating physician and discussed with the primary investigator prior to enrollment.
1.2 Prior Therapy Patients must have recurred/progressed following prior standard therapy for their tumor. Note: Patients with meningioma, atypical meningioma, or anaplastic meningioma must have received at least surgical resection or radiation.
1.3 Screening Consent Participant/legal guardian is willing to sign a screening consent for \[68Ga\]Ga-DOTATATE PET imaging. The screening consent is to be obtained according to institutional guidelines. Assent, when appropriate, will be obtained according to institutional guidelines.
2. Eligibility Criteria
* Phase I Age Patient must be ≥ 4 and \<12 years of age at the time of enrollment. Disease Status: Patients who participate in the efficacy expansion cohort must have bi-dimensionally measurable disease, defined as at least one lesion that can be accurately measured in at least two dimensions Patients with measurable extraneural disease only are also eligible.
* Phase II Age Patient must be 12 to \</=39 years at the time of enrollment.
3. Inclusion Criteria
3.1 Uptake on \[68Ga\]Ga-DOTATATE PET Patients must have uptake on DOTATATE PET/CT in at least one tumor lesion (corresponding to known disease) equivalent to a Krenning score ≥2 (confirmed by central radiology review).
3.2 Prior Therapy Patients must have recovered from the acute treatment related toxicities (defined as ≤ grade 1 if not defined in eligibility criteria) of all prior chemotherapy, immunotherapy, radiotherapy, or any other treatment modality prior to entering this study.
3.3 Chemotherapy Patients must have received their last dose of known myelosuppressive anticancer therapy at least 21 days prior to enrollment or at least 42 days if nitrosourea.
3.4 Investigational/Biologic Agent
●Biologic or investigational agent (anti-neoplastic): Patient must have recovered from any acute toxicity potentially related to the agent and received their last dose of the investigational or biologic agent ≥ 7 days prior to study enrollment.
For agents that have known adverse events occurring beyond 7 days after administration, this period must be extended beyond the time during which adverse events are known to occur.
●Monoclonal Antibodies and agents with known prolonged half-lives: Patient must have recovered from any acute toxicity potentially related to the agent and received their last dose of the agent ≥ 28 days prior to study enrollment.
3.5 Radiation
Patients must have had their last fraction of:
* Craniospinal irradiation or total body irradiation or radiation to \> 50% of pelvis \> 3 months prior to enrollment.
* Focal irradiation \> 4 weeks prior to enrollment
3.6 Stem Cell Transplant
Patient must be:
* ≥ 6 months since allogeneic stem cel
NCT07621692Phase 1Recruiting
National Taiwan University Hospital · National Taiwan University Cancer Center, Taipei
This study is a phase I dose escalation clinical trial aims to evaluate 161Tb-PSMA-I\&T, a new generation prostate-specific membrane antigen (PSMA)-targeted radioligand therapy (RLT) using Terbium-161 to replace Lutetium-177, its safety, dosimetry, biodistribution, pharmacokinetics, and preliminary efficacy in Taiwanese men with metastatic castration-resistant prostate cancer, and to inform future clinical trials.
Eligibility: 20 Years to · Male · 1. Age ≥ 20 years, ability to understand and willingness to sign informed consent, cooperate with all study-related procedures and assessments including blood tests and imaging
2. Histologically confirmed adenocarcinoma of the prostate with evidence of metastatic castration-resistant prostate cancer (mCRPC)
3. Prior surgical orchiectomy or chemical castration maintained on luteinizing hormone-releasing hormone analog, with a serum testosterone level \<50 ng/dL (castrate range)
4. Prior treated with at least one line of taxane-based chemotherapy unless medically unsuitable, and at least one line of androgen receptor pathway inhibitor (e.g., abiraterone, enzalutamide, apalutamide, or darolutamide)
5. Prior treated with 177Lu-labeled PSMA RLT unless medically unsuitable or declined by the patient
6. Progressive disease defined according to Prostate Cancer Clinical Trials Working Group 3: Either a PSA progression of more than 2 rising PSA values from baseline with intervals ≥ 1 week, or a soft-tissue progression on images per RECIST 1.1 criteria, or a bone progression on images with more than 2 new lesions
7. Evidence of significant PSMA-avid lesions on 68Ga- or 18F-labeled PSMA PET/CT within 12 weeks prior to screening, which defined as 68Ga-PSMA or 18F-PSMA uptake greater than that of liver or spleen parenchyma (depend on the tracer used) in at least one metastatic lesion of any size in any organ system
8. A life expectancy of ≥ 6 months and Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
9. Adequate bone marrow and organ functions 9.1 Hemoglobin ≥ 10 g/dL without RBC transfusion within 4 weeks 9.2 Absolute neutrophil count ≥ 1.5 × 109/L 9.3 Platelet count ≥ 150 × 109/L 9.4 Creatinine clearance ≥ 50 mL/min (Cockcroft-Gault) 9.5 AST and ALT ≤ 3 × ULN, total bilirubin ≤ 1.5 × ULN
10. Willingness to comply with the use of medically acceptable forms of barrier contraception if sexually active
NCT05803941Phase 4Recruiting
Novartis Pharmaceuticals · Mayo Clinic Arizona, Scottsdale, Arizona
The purpose of this post-marketing study is to further characterize the long-term outcome of known or potential risks of lutetium (177Lu) vipivotide tetraxetan also known as \[177Lu\]Lu-PSMA-617 or 177Lu-PSMA-617 and hereinafter referred to as AAA617. The study also seeks to further characterize (as possible) any other AAA617 causally related serious adverse event(s) in the long-term in adults with prostate cancer who received at least one dose of AAA617 from interventional, Phase I-IV Novartis sponsored clinical trials.
Eligibility: 18 Years to 100 Years · Male · * Signed informed consent must be obtained prior to participation in the study
* Must have received at least one dose of AAA617 within an interventional, Phase I-IV Novartis sponsored clinical trial in prostate cancer and have fulfilled the trial's requirements that allows them to participate in this study.
NCT05413850Phase 1, Phase 2Recruiting
Blue Earth Therapeutics Ltd · Biogenix Molecular LLC, Miami, Florida
To determine the dose, safety, radiation dosimetry and efficacy of 177Lu-rhPSMA-10.1 in participants with PSMA-expressing metastatic castrate resistant prostate cancer.
Eligibility: 18 Years to · Male · 1. Male subjects, 18 years of age or older with histologically confirmed adenocarcinoma of the prostate.
2. Serum testosterone levels \<50 ng/dL (1.73 nmol/L) after surgical or continued chemical castration.
3. Presence of disease target or non target lesions (per RECIST v1.1) on CT/MRI and/or presence of disease on full body 99mTc bone scan performed within 28 days of screening.
4. Positive disease expression of PSMA as confirmed on PSMA PET/CT scan.
5. At least 4 weeks or 5 half-lives (whichever is longer) elapsed between last anti-cancer treatment administration and the initiation of study treatment (except for Luteinising Hormone-releasing Hormone or GnRH).
6. Resolution of all previous treatment related toxicities to CTCAE version 5.0 grade of ≤1 (except for chemotherapy induced alopecia and grade 2 peripheral neuropathy or grade 2 urinary frequency which are allowed).
7. Prior major surgery must be at least 12 weeks prior to study entry.
8. Eastern Cooperative Oncology Group (ECOG) performance status of 0-2 with a life expectancy ≥6 months.
9. Adequate bone marrow reserve and organ function as demonstrated by blood count, and serum biochemistry at baseline.
10. Adequate contraception for patients and their partners.
11. For Phase 1 mCRPC only: Subjects who have experienced disease progression on or after at least 1 NAAD (e.g. abiraterone, enzalutamide) and at least 1 course (but no more than 2 courses) of taxane-based chemotherapy. For Phase 2 mCRPC only: Subjects who have experienced disease progression on or after at least 1 NAAD (e.g. abiraterone, enzalutamide, apalutamide, darolutamide), but have not received previous taxane-based chemotherapy for the treatment of mCRPC.
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
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.
