EUCTR2017-004034-29-GBActive, not recruitingPhase 1
A Phase I/II open-label, multi-center, dose-escalation study of safety, tolerability, pharmacokinetics, dosimetry, and response to repeat dosing of 177Lu-PSMA-R2 radio-ligand therapy in patients with prostate specific membrane antigen (PSMA) positive (68Ga-PSMA-R2) progressive metastatic castration-resistant prostate cancer, following previous systemic treatment. - PROter
Advanced Accelerator Applications International SA0 sites110 target enrollmentStarted: May 2, 2018Last updated:
Conditions
Trial Snapshot
- Phase
- Phase 1
- Status
- Active, not recruiting
- Enrollment
- 110
Study Overview
Brief Summary
No summary available.
Study Design
- Study Type
- Interventional clinical trial of medicinal product
Eligibility Criteria
- Sex
- Male
Inclusion Criteria
- •1. Male patients, 18 years of age or older
- •2. Signed and dated written ICF by the patient prior to any study-specific procedures.
- •3. Histologically confirmed adenocarcinoma of the prostate.
- •4. Serum testosterone levels < 50 ng/dL after surgical or continued chemical castration
- •5. Metastatic disease documented by CT/MRI or bone scan revealing at least one metastatic lymph-node, visceral metastasis and/or bone metastasis
- •6. Positive 68Ga-PSMA-R2 PET/CT scan for central eligibility assessment. This scan must not be older than 28 days at enrollment and demonstrate metastatic disease. Patients who receive 68Ga-PSMA-R2 as part of separate clinical protocol are eligible (must meet all study eligibility criteria)
- •7. Documented progressive mCRPC after the last prior systemic treatment administered for metastatic disease. Disease progression is defined as increasing serum PSA (per PCWG3), radiological progression or = 2 new bone lesions.
- •8.Must have received prior systemic therapy for mCRPC with CYP 17 inhibitors and/or androgen-pathway inhibitors (i.e. abiraterone and/or enzalutamide when available).
- •9.Must have received one but no more than one line of chemotherapy for the advanced disease or patients who were ineligible (unfit or unwilling) to receive chemotherapy.
- •10. At least 28 days elapsed between last anti-cancer treatment administration and the initiation of study treatment (except for Luteinizing Hormone-releasing Hormone [LHRH] or Gonadotropin-releasing Hormone [GnRH]), or 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). Prior major surgery must be at least 12 weeks prior to study entry.
- •11. Eastern cooperative oncology group (ECOG) performance status of 0-2 with a life expectancy = 6 months
- •12. Adequate bone marrow reserve and organ function as demonstrated by complete blood count, and biochemistry in blood and urine at baseline
- •a. Platelet count of >100 x10^9/L
- •b. White blood cell (WBC) count > 3,000/mL
- •c. Neutrophil count of > 1,500/mL
- •d. Hemoglobin = 10 g/dL
- •e. Serum creatinine < 1.5 x ULN or estimated GFR > 50 mL/min based upon Chronic Kidney Disease-Epidemiology Collaboration (CKD-EPI) equation. Patients with estimated GFR between 50 - 60 mL/min at baseline will require a 99mTc-DTPA GFR test and only patients with non-obstructive pathology will be included in the study.
- •f. Total bilirubin < 3 x ULN (except if confirmed history of Gilbert’s disease)
- •g. Baseline serum albumin > 30 g/L
- •h. Aspartate aminotransferase (AST) < 3 times the ULN
- •13. For male patients with partners of childbearing potential, agreement to use barrier contraceptive method (condom) and to continue its use for 6 months from receiving the last dose of IMP.
- •Are the trial subjects under 18? no
- •Number of subjects for this age range:
- •F.1.2 Adults (18-64 years) yes
- •F.1.2.1 Number of subjects for this age range 30
- •F.1.3 Elderly (>=65 years) yes
- •F.1.3.1 Number of subjects for this age range 66
Exclusion Criteria
- •1. Pathological finding consistent with small cell, neuroendocrine carcinoma of the prostate, or any other histology different than adenocarcinoma.
- •2. Diffuse bone-marrow involvement (i.e. superscan” defined as bone scintigraphy in which there is excessive skeletal radioisotope uptake [>20 bone lesions] in relation to soft tissues along with absent or faint activity in the genitourinary tract due to diffuse bone/ bone marrow metastases).
- •3. Prior exposure to radioligand therapy, radioisotope therapy (e.g. 89Sr), systemic radiotherapy, or 223Ra-therapy.
- •4. Current severe urinary incontinence, hydronephrosis, severe voiding dysfunction, any level of urinary obstruction requiring indwelling/condom catheters
- •5. Spinal cord compression or brain metastases
- •6. Uncontrolled pain that results in patient lack of compliance with the imaging procedures
- •7. Uncontrolled cardiovascular history, defined as:
- •Congestive heart failure (New York Heart Association [NYHA] II, III, IV)
- •Mean resting corrected QT interval (QTc) >450 millisecond (msec), obtained from 3 ECGs recordings, using the screening clinic ECG machine-derived QTc value.
- •Any clinically important abnormalities in rhythm, conduction, or morphology of resting ECG (e.g., complete left bundle branch block, third-degree heart block, second-degree heart block, PR interval >250 msec).
- •Any factor increasing the risk of QTc prolongation or risk of arrhythmic events such as heart failure, hypokalemia, congenital long QT syndrome, family history of long QT syndrome, or unexplained sudden death under 40 years of age in first-degree relatives, or any concomitant medication known to prolong the QT interval.
- •8. Other known co-existing malignancies except non-melanoma skin or low grade superficial bladder cancer unless definitively treated and proven no evidence of recurrence for 5 years.
- •9. History of deep vein thrombosis and/or pulmonary embolism within 4 weeks of enrollment.
- •10. Known incompatibility to CT or PET scans.
- •11. Any evidence of severe or uncontrolled systemic or psychiatric diseases, including uncontrolled hypertension and active bleeding diatheses, which in the Investigator’s opinion makes it undesirable for the patient to participate in the trial or which would jeopardize compliance with the protocol
- •12. Active infection including human immunodeficiency virus (HIV) and untreated hepatitis B, and hepatitis C. Screening for chronic conditions is not required.
- •13. Patients who have received any investigational agent within the last 28 days.
- •14. Known allergies, hypersensitivity, or intolerance to the IP or its excipients
- •15. Known history of myelodysplastic syndrome/leukemia at any time
- •16. Patient is unlikely to comply with study procedures, restrictions and requirements and judged by the Investigator that the patient is not suitable for participation in the study.
Investigators
Similar Trials
Active, not recruiting
Phase 1
Phase I/Ib study of GWN323 alone and in combination with PDR001 in patients with advanced malignancies and lymphomasSolid tumors and lymphomasEUCTR2015-004206-42-GBovartis Pharma Services AG264
Active, not recruiting
Phase 1
Phase I/Ib study of GWN323 alone and in combination with PDR001 in patients with advanced malignancies and lymphomasSolid tumors and lymphomasEUCTR2015-004206-42-ESovartis Pharma Services AG264
Recruiting
Phase 1
A Phase-I dose escalation study to evaluate Safety of NRC-1111.CTRI/2023/03/051121ATCO Pharma Ltd
Active, not recruiting
Phase 1
A safety and efficacy study in Children with Metachromatic Leukodystrophy recieving enzyme (HGT-1110) replacement by intrathecal injectioEUCTR2011-002044-28-DEShire Human Genetics Therapies Inc24
Active, not recruiting
Phase 1
A safety and efficacy study in Children with Metachromatic Leukodystrophy recieving enzyme (HGT-1110) replacement by intrathecal injectioEUCTR2011-002044-28-DKShire Human Genetics Therapies Inc24