Clinical Trial · NCT03490838

177Lu-PSMA-R2 in Patients With PSMA Positive Progressive, Metastatic, Castration Resistant Prostate Cancer

Overview

This Phase 1/2 study is intended to investigate the safety, tolerability, and radiation dosimetry of 177Lu-PSMA-R2 and further assess preliminary efficacy data in patients with metastatic castration-resistant prostate cancer (mCRPC). The Phase 1 portion of the study will determine the recommended dose of 177Lu-PSMA-R2 for radio-ligand therapy (RLT) of mCRPC, and the Phase 2 portion will expand into approximately 60 patients documenting the preliminary activity (anti-tumor response) of repeated treatments administered, continuing safety assessments and collecting QoL data.

Sponsor

Advanced Accelerator Applications

Phase

Phase 1

Contacts

Novartis Pharmaceuticals (STUDY_DIRECTOR)

ClinicalTrials.gov

NCT03490838

Drug / Compound

PSMA-R2

Isotope(s):

Target(s):

PSMA

Ligand Class: Small Molecules

Chelator: DOTA

PSMA-R2

Isotope(s):

Target(s):

PSMA

Ligand Class: Small Molecules

Chelator: DOTA

Eligibility

Inclusion

Baseline serum albumin \> 30 g/L
Hemoglobin ≥ 10 g/dL
Serum testosterone levels \< 50 ng/dL after surgical or continued chemical castration
Metastatic disease documented by CT/MRI or bone scan (not older than 28 days at enrollment) revealing at least one metastatic lymph-node, visceral metastasis and/or bone metastasis
Adequate bone marrow reserve and organ function as demonstrated by complete blood count, and biochemistry in blood and urine at baseline
Serum creatinine \< 1.5 x upper limit normal (ULN) or estimated glomerular filtration rate (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.
Must have received prior systemic treatment for mCRPC including CYP17 inhibitors and/or androgen-pathway inhibitors (i.e. abiraterone and/or enzalutamide when available) and one and no more than one line of chemotherapy for the advanced disease (unless ineligible (unfit) to receive chemotherapy).
Histologically confirmed adenocarcinoma of the prostate
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 IP
Documented progressive mCRPC on or after the last systemic treatment administered for the advanced disease including metastatic disease. Disease progression defined as increasing serum PSA (per PCWG3), radiological progression or ≥ 2 new bone lesions.
White blood cell (WBC) count \> 3,000/mL
Platelet count of \>100 x10e9/L
Eastern cooperative oncology group (ECOG) performance status of 0-2 with a life expectancy ≥ 6 months
Aspartate aminotransferase (AST) \< 3 times the ULN
Positive 68Ga-PSMA-R2 PET/CT scan for central eligibility assessment. Patients who receive 68Ga-PSMA-R2 as part of separate clinical protocol are eligible (must meet all study eligibility criteria)
Total bilirubin \< 3 x ULN (except if confirmed history of Gilbert's disease)
Neutrophil count \> 1,500/mL
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.

Exclusion

Known allergies, hypersensitivity, or intolerance to the IP or its excipients
Pathological finding consistent with small cell, neuroendocrine carcinoma of the prostate or any other histology different than adenocarcinoma.
Prior exposure to radioligand therapy radioisotope therapy (e.g. 89Sr), systemic radiotherapy or 223Ra-therapy.
Congestive heart failure (New York Heart Association \[NYHA\] II, III, IV)
Active infection including human immunodeficiency virus (HIV) and untreated hepatitis B, and hepatitis C. Screening for chronic conditions is not required.
Uncontrolled cardiovascular history, defined as:
Current severe urinary incontinence, hydronephrosis, severe voiding dysfunction, any level of urinary obstruction requiring indwelling/condom catheters
History of deep vein thrombosis and/or pulmonary embolism within 4 weeks of enrollment.
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 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
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.
Uncontrolled pain that results in patient's lack of compliance with the imaging procedures
Patients who have received any investigational treatment agent within the last 28 days.
Mean resting corrected QT interval (QTc) \>450 millisecond (msec), obtained from 3 ECGs recordings, using the screening clinic ECG machine-derived QTc value.
Spinal cord compression or brain metastases
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)
Known incompatibility to CT or PET scans.