A study in men with advanced prostate cancer to determine the safety and effects of a test drug (Lutetium (177Lu) rhPSMA 10.1 injection)
- Conditions
- PSMA-positive metastatic castration-resistant prostate cancer (mCRPC)MedDRA version: 21.1Level: LLTClassification code 10076506Term: Castration-resistant prostate cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2022-002407-37-DE
- Lead Sponsor
- Blue Earth Therapeutics Limited
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- Male
- Target Recruitment
- 156
1. Male subjects, 18 years of age or older.
2. Willing to provide signed and dated written informed consent form (ICF) prior to any study-specific procedures.
3. Willing to comply with required lifestyle restrictions following administration of the IMP per local regulations.
4. Histologically confirmed adenocarcinoma of the prostate.
5. Serum testosterone levels <50 ng/dL (1.73 nmol/L) after surgical or continued chemical castration.
6. Meets respective cohort-specific inclusion criterion for Phase 2 only.
7. Presence of disease target or non-target lesions (per RECIST v1.1) on CT/MRI and/or full body 99mTc bone scan performed within 28 days of screening.
8. Positive disease expression of PSMA as confirmed on rhPSMA-7.3 (18F) PET/CT scan. Note: For Phase 1, LOCAMETZ® or a positive PSMA PET/CT scan which has already been obtained within 4 weeks (28 days) prior to screening may be used for subject selection in Phase 1.
Note: Positive disease is defined as having at least 1 PSMA-positive lesion of any size with higher uptake than normal liver using visual assessment. The lesion can be bone, lymph node or viscera. At least one PSMA-positive lesion should be visible on the CT/MRI and =1.5 cm in the short axis (Phase 1 only). Further details regarding the interpretation of the diagnostic images can be found in the Image Acquisition Guidelines.
9. At least 28 days 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).
10. 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).
11. Prior major surgery must be at least 12 weeks prior to study entry.
12. Eastern Cooperative Oncology Group (ECOG) performance status of 0-2 with a life expectancy =6 months.
13. Adequate bone marrow reserve and organ function as demonstrated by blood count, and serum biochemistry at baseline:
- Platelet count = 150 × 109/L
- WBC count = 3.0 × 109/L
- Neutrophil count of = 1.5 × 109/L
- Haemoglobin = 10 g/dL
- Estimated glomerular filtration rate (using Chronic Kidney Disease Epidemiology Collaboration Creatinine Equation [2009]) (Levey 2009) =60 mL/min
- Total bilirubin <1.5× ULN (except if confirmed history of Gilbert's disease)
- Serum albumin =30 g/L
- AST <2× the ULN
- ALT <2× the ULN
14. Male subjects must not father children or donate sperm during the study and for at least 6 months after the last study treatment. In addition, they must agree to use effective contraception for this same period to protect partners from any exposure to the IMP. For males with partners who are of childbearing potential, effective contraception is a combination of male condom with either cap, diaphragm, or sponge with spermicide (double barrier methods). A man is only considered to be infertile if he has had bilateral orchidectomy or successful vasectomy with laboratory confirmed aspermia.
15. Cohort-specific inclusion criteria:
a) Phase 1 and Phase 2 mCRPC: 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.
b) Phase 2 mCRPC: Subjects who have experienced disease progression on or after at least 1 NAAD (e.g. ab
1. Known hypersensitivity to the therapeutic or diagnostic IMP or any of its constituents.
2. Presence of PSMA-negative disease: PSMA-negative disease defined as any large PSMA-negative lymph node >1 cm in the short axis and/or a PSMA-negative bone metastasis which has a significant soft tissue component suggesting ongoing disease activity and/or a PSMA-negative solid organ metastasis >1 cm in the long axis. In addition, subjects with significant low PSMA-expressing disease should be excluded. Further details are provided in the Image Acquisition Guidelines.
3. Diffuse marrow infiltration of disease (‘superscan’ appearance on full body 99mTc bone scan). A superscan is defined as bone scintigraphy in which there is excessive skeletal radioisotope uptake in relation to soft tissues along with absent or faint activity in the genitourinary tract and soft tissues due to diffuse bone/bone marrow metastases. Further details regarding this appearance are provided in the Image Acquisition Guidelines.
4. Symptomatic spinal cord compression, or clinical or radiological findings that are indicative of impending spinal cord compression.
5. Known history of haematological malignancy.
6. Known history of central nervous system (CNS) metastases.
Exception: Subjects with a history of CNS metastases who have received and completed therapy (e.g. surgery, radiotherapy), and are neurologically stable, asymptomatic and do not require corticosteroids or anti-convulsants to control neurological symptoms will be eligible. Discrete dural metastases are permitted but diffuse leptomeningeal disease is not. For subjects with a history of CNS metastases, baseline imaging and subsequent radiological imaging for assessing treatment response must include MRI or ceCT evaluation of the brain.
7. Histological findings consistent with neuroendocrine phenotype of prostate cancer.
8. Known history of other solid malignancy that may reduce life expectancy and/or may interfere with disease assessment.
Exception: Subjects with histopathologically confirmed prior malignancy that has been treated, and who have been disease-free for >3 years. Subjects with treated non-melanoma skin cancer and non-muscle invasive bladder cancer will be eligible.
9. Unresolved urinary tract obstruction defined as radiographic evidence of hydronephrosis with or without ureteric stent/nephrostomy. Where the clinical team judges that the subject’s hydronephrosis is not obstructing, and renal function meets the inclusion criteria, the subject may undergo 99mTc mercaptoacetyltriglycerine scanning during the screening period and if the result is non-obstructed, the subject can be eligible for the study.
10. Any uncontrolled significant medical, psychiatric, or surgical condition or laboratory finding that would pose a risk to subject safety or interfere with study participation or interpretation of individual subject results. For cardiac conditions, this includes, but is not limited to, New York Heart Association class III or IV congestive heart failure, history of congenital prolonged QT syndrome, and myocardial infarction diagnosed within 6 months prior to enrolment.
11. Ongoing treatment with bisphosphonates for bone-targeted therapy.
Exception: Subjects will be eligible if they have received a stable dose of zoledronic acid for at least 8 weeks prior to enrolment. These subjects must have had renal function monitored since initiation of bisphosphonate therapy, with a stable pattern observed, and must
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