Phase I/II trial of repeated dosing of therapeutic investigational product 177Lu-PSMA-R2 and imaging agent 68Ga-PSMA-R2 in patients with prostate cancer that has spread. The study will assess the safety of the therapeutic drug and how it is tolerated by the body, the movement of the therapeutic study drug and imaging agent in the body and the quantity of radioactivity taken by the organs and tumors.
- Conditions
- Patients with PSMA positive Metastatic Castration-resistant Prostate Cancer (mCRPC), and disease progression following previous systemic treatment for mCRPC.MedDRA version: 20.0Level: HLTClassification code 10036908Term: Prostatic neoplasms malignantSystem Organ Class: 100000004864Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2017-004034-29-GB
- Lead Sponsor
- Advanced Accelerator Applications International SA
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- Male
- Target Recruitment
- 110
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
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.
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method