Prostatic NeoplasmPhase 1PROterNCT03490838
177Lu-PSMA-R2 in Patients With PSMA Positive Progressive, Metastatic, Castration Resistant Prostate Cancer
A Phase 1 study testing 177Lu-PSMA-R2 in people with Prostatic Neoplasm, run by Advanced Accelerator Applications at 11 sites in 2 countries.
Trial summary
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). Read more about this study
- Who is it for?
- Ages 18 years and older, men only
- Conditions the study is for
- Prostatic Neoplasm
- What is being tested?
- 177Lu-PSMA-R2
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 27 participants
- Where
- 11 sitesin 2 countries
- Study dates
- 24 May 2018to 2 Jun 2022
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- Men only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Male patients, 18 years of age or older
- Signed and dated written ICF by the patient or legally acceptable representative prior to any study-specific procedures
- Histologically confirmed adenocarcinoma of the prostate
- 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
- 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)
Show all 20Show fewer
- 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.
- 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).
- 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.
- Eastern cooperative oncology group (ECOG) performance status of 0-2 with a life expectancy ≥ 6 months
- Adequate bone marrow reserve and organ function as demonstrated by complete blood count, and biochemistry in blood and urine at baseline
- Platelet count of >100 x10e9/L
- White blood cell (WBC) count > 3,000/mL
- Neutrophil count > 1,500/mL
- Hemoglobin ≥ 10 g/dL
- 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.
- Total bilirubin < 3 x ULN (except if confirmed history of Gilbert's disease)
- Baseline serum albumin > 30 g/L
- Aspartate aminotransferase (AST) < 3 times the ULN
- 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
Who cannot join
- Pathological finding consistent with small cell, neuroendocrine carcinoma of the prostate or any other histology different than adenocarcinoma.
- 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)
- Prior exposure to radioligand therapy radioisotope therapy (e.g. 89Sr), systemic radiotherapy or 223Ra-therapy.
- Current severe urinary incontinence, hydronephrosis, severe voiding dysfunction, any level of urinary obstruction requiring indwelling/condom catheters
- Spinal cord compression or brain metastases
- Uncontrolled pain that results in patient's lack of compliance with the imaging procedures
Show all 20Show fewer
- 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.
- Other known co-existing malignancies except non-melanoma skin cancer or low grade superficial bladder cancer unless definitively treated and proven no evidence of recurrence for 5 years.
- History of deep vein thrombosis and/or pulmonary embolism within 4 weeks of enrollment.
- Known incompatibility to CT or PET scans.
- 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
- Active infection including human immunodeficiency virus (HIV) and untreated hepatitis B, and hepatitis C. Screening for chronic conditions is not required.
- Patients who have received any investigational treatment agent within the last 28 days.
- Known allergies, hypersensitivity, or intolerance to the IP or its excipients
- Known history of myelodysplastic syndrome/leukemia at any time
- 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.
Trial locations and contacts
11 sites in 2 countries.
11 sites in 2 countries
United States9 sites
John Hopkins University - Kimmel Comp. Cancer Center
Baltimore, Maryland, 21231
National Institute of Health
Bethesda, Maryland, 20892
University of Wisconsin / Paul P. Carbone Comp Cancer Center
Madison, Wisconsin, 53792
Yale New Haven Children Hospital
New Haven, Connecticut, 06520
Tulane Cancer Center Tulance Cancer
New Orleans, Louisiana, 70112
Mount Sinai Hospital School of Medicine
New York, New York, 10029
Pheonix Molecular Imaging Center
Phoenix, Arizona, 85040
University of California San Francisco
San Francisco, California, 94158
Stanford University Medical Center
Stanford, California, 94305
Spain2 sites
Hospital Vall Hebrón
Barcelona
Hospital Universitario 12 de Octubre
Madrid
About this study
Official title: A Phase 1/2 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
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.
Read the detailed description
Recruitment for PROter A206T-G01-001 (NCT03490838) was halted in Phase I by sponsor decision. Phase II expansion portion of the study was never initiated. Importantly, this recruitment halt was not a consequence of any safety concern. Ongoing patients at the time of recruitment halt continued per protocol and completed the 1 year safety follow-up prior to early study termination.
The primary objective of the Phase I portion of the study to assess the safety and tolerability of 177Lu-PSMA-R2 and to assess Dose Limiting Toxicities (DLTs) and determine the maximum tolerated dose (MTD) (if reached) and the recommended Phase II dose was not reached due to early recruitment halt.
- Conditions
- Prostatic Neoplasm
- Being tested
- 177Lu-PSMA-R2
- Keywords
- Genital Neoplasms, Male, Urogenital Neoplasms, Neoplasms by Site, Neoplasms, Prostatic Diseases, Cancer of Prostate, Cancer of the Prostate, Neoplasms, Prostate, Neoplasms, Prostatic, Prostate Cancer, Prostate Neoplasms, Prostatic Cancer, Prostate-Specific Membrane Antigen, PSMA, PSMA radioligand therapy
- Medical subject headings
- Prostatic Neoplasms, Genital Neoplasms, Male, Urogenital Neoplasms, Neoplasms by Site, Neoplasms, Prostatic Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
177Lu-PSMA-R2Drug
radio-ligand therapy
| Study group | Role | What they receive |
|---|---|---|
| Phase I: Dose Escalation Cohort 1 | Experimental | 3.70 GBq (100 mCi) x 3 times Receives: Drug: 177Lu-PSMA-R2 |
| Phase I: Dose Escalation Cohort 2 | Experimental | 7.40 GBq (200 mCi) up to 4 times Receives: Drug: 177Lu-PSMA-R2 |
| Phase I: Dose Escalation Cohort 3 | Experimental | 11.1 GBq (300 mCi) up to 4 times Receives: Drug: 177Lu-PSMA-R2 |
| Phase I: Dose Escalation Cohort 4 | Experimental | 14.8 GBq (400 mCi) up to 4 times Receives: Drug: 177Lu-PSMA-R2 |
| Phase I: Dose Escalation Cohort 5 | Experimental | 18.5 GBq (500 mCi) up to 4 times Receives: Drug: 177Lu-PSMA-R2 |
| Phase I: Dose Escalation Cohort 6 | Experimental | 18.5 GBq (500 mCi) up to 3 times Receives: Drug: 177Lu-PSMA-R2 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Phase I: Incidence of dose limiting toxicities (DLTs) during first cycle of study treatment.
A dose-limiting toxicity (DLT) is defined as any toxicity not attributable to the disease or disease-related processes under investigation, the time window for DLT assessment period is Cycle 1. To be considered a DLT, it must be related to the IP (attributions: possible, probable, and definite) while fulfilling one of the following criteria as per the NCI Common Toxicity Criteria for Adverse Events (CTCAE) version 5.0.
Measured: Up to 8 weeks after the first 177Lu-PSMA-R2 dose
Phase II: Prostate-Specific Antigen (PSA) response rate 50
PSA response rate 50 is defined as the proportion of participants who have a greater or equal 50% in PSA from Baseline that is confirmed by a second PSA measurement 4 weeks later, as per Prostate Cancer Working Group 3 (PCWG3) criteria.
Measured: Week 13 (12 weeks after the first 177Lu-PSMA-R2 injection)
Secondary outcomes (19)
Phase I and II: Treatment Emergent Adverse Event (TEAE) rate
The distribution of adverse events will be done via the analysis of frequencies for treatment emergent Adverse Event (TEAEs), Serious Adverse Event (TESAEs) and Deaths due to AEs, through the monitoring of relevant clinical and laboratory safety parameters.
Measured: From randomization till 30 days safety follow-up, assessed up to 4 years (estimated final OS analysis)
Phase I and II: Objective Response Rate (ORR)
ORR is defined as the proportion of participants with Best Overall Response (BOR) of Complete Response (CR) or Partial Response (PR) per RECIST 1.1.
Measured: From date of randomization assessed up to 4 years (estimated final OS analysis)
Phase I and II: Duration of Response (DoR)
Duration of Response (DoR) according to RECIST v1.1 is defined as the time that measurement criteria are met for objective response (CR/PR) (whichever status is recorded first) until the first date of progression or death is documented.
Measured: From date of randomization until date of progression or date of death from any cause, whichever come first, assessed up to 4 years (estimated final OS analysis)
Phase I and II: Prostate-Specific Antigen (PSA) response rate 30
PSA response rate 30 is defined as the proportion of participants who have a greater or equal 30% in PSA from Baseline that is confirmed by a second PSA measurement 4 weeks later, as per Prostate Cancer Working Group 3 (PCWG3) criteria.
Measured: Week 13 (12 weeks after the first 177Lu-PSMA-R2 injection)
Phase I: Prostate-Specific Antigen (PSA) response rate 50
PSA response rate 50 is defined as the proportion of participants who have a greater or equal 50% in PSA from Baseline that is confirmed by a second PSA measurement 4 weeks later, as per Prostate Cancer Working Group 3 (PCWG3) criteria.
Measured: Week 13 (12 weeks after the first 177Lu-PSMA-R2 injection)
Phase I: 177Lu-PSMA-R2 plasma concentration
Measured: Days 1 through 8 post-treatment
Phase I: Maximum plasma concentration (Cmax) of 177Lu-PSMA-R2
Venous whole blood samples will be collected for activity-based pharmacokinetics characterization. Cmax will be listed and summarized using descriptive statistics.
Measured: Day 1 (before the start of infusion, at the mid-point, and just before the end of infusion, then at post infusion at approximately 5, 15, 30 minutes, 1, 2, 4, 6, 8, 24, 40 (+/- 4 hours), 48 hours), Day 4 (+2 days) and Day 8 post end of infusion
Phase I: Minimum plasma concentration (Cmin) of 177Lu-PSMA-R2
Venous whole blood samples will be collected for activity-based pharmacokinetics characterization. Cmin will be listed and summarized using descriptive statistics.
Measured: Day 1 (before the start of infusion, at the mid-point, and just before the end of infusion, then at post infusion at approximately 5, 15, 30 minutes, 1, 2, 4, 6, 8, 24, 40 (+/- 4 hours), 48 hours), Day 4 (+2 days) and Day 8 post end of infusion
Phase I: Area under the plasma concentration-time curve (AUC) of 177Lu-PSMA-R2
Venous whole blood samples will be collected for activity-based pharmacokinetics characterization. AUC will be listed and summarized using descriptive statistics.
Measured: Day 1 (before the start of infusion, at the mid-point, and just before the end of infusion, then at post infusion at approximately 5, 15, 30 minutes, 1, 2, 4, 6, 8, 24, 40 (+/- 4 hours), 48 hours), Day 4 (+2 days) and Day 8 post end of infusion
Phase I: Dosimetry
Radiation (Gy, Gy/MBq) update by critical organs and metastatic lesions
Measured: Days 1 through 8 post-treatment
Phase I and II: Patient Reported Outcomes (PRO) of Mouth Dryness using Xerostomia Questionnaire
The Xerostomia questionnaire is a questionnaire used to describe mouth dryness and its effects on daily life. It consists of 8 questions with each question score ranging from 0 ("never"/"none") to 10 ("worst"). The sum of the 8 scores produces a total score (score range from 0-80). A low score corresponds to a good quality of life while a high score means a poor quality of life due to the dry mouth.
Measured: Prior to dosing on Day 1 and every 12 weeks until 1 year after disease progression or early study termination whichever comes first
Phase I and II: Patient Reported Outcomes (PRO) of Eye Dryness using Xerophthalmia Questionnaire
The Xerophthalmia questionnaire is a questionnaire used to describe eye dryness and its effects on daily life. It consists of 3 questions. The first 2 questions scores range from 1 ("never") to 4 ("constantly") and the last question is a Yes/No question about previous dry eye diagnosis. The sum of the scores of the first 2 questions produces a total score (score range from 2-8). A low score corresponds to a good quality of life while a high score means a poor quality of life due to the dry eye.
Measured: Prior to dosing on Day 1 and every 12 weeks until 1 year after disease progression or early study termination whichever comes first
Phase I and II: Brief Pain Inventory-short Form (PBI-SF)
The BPI-SF is a publicly available instrument to assess the pain and includes severity and interference scores. BPI-SF is an 11-item self report questionnaire that is designed to assess the severity and impact of pain on daily functions of a participant. Pain severity score is a mean value for BPI-SF questions 3, 4, 5 and 6 (questions inquiring about the extent of pain, where the extent is ranked from 0 [no pain] to 10 [pain as bad as you can imagine]). Pain severity progression is defined as an increase in score of 30% or greater from baseline without decrease in analgesic use.
Measured: Prior to dosing on Day 1 and every 12 weeks until 1 year after disease progression or early study termination whichever comes first
Phase II: Disease Control Rate (DCR)
DCR is defined as the proportion of participants with Best Overall Response (BOR) of Complete Response (CR), Partial Response (PR), or Stable Disease (SD) per RECIST 1.1.
Measured: From date of randomization till 30 days safety fup, assessed up to 4 years (estimated final OS analysis)
Phase II: Radiographic Progression Free Survival (rPFS)
rPFS is defined as the time to radiographic progression by PCWG3-modified RECIST v1.1 or death.
Measured: From date of randomization until date of radiographic progression or date of death from any cause, whichever comes first, assessed up to 4 years (estimated final OS analysis)
Phase II: Overall Survival (OS)
OS is defined as the time to death for any cause.
Measured: From date of randomization until date of death from any cause, assessed up to 4 years (estimated final OS analysis)
Phase II: Time to Prostate Specific Antigen (PSA) progression
PSA progression is defined as the time from the date of first dose of 177Lu-PSMA-R2 injection to the first date that a >= 25% increase in PSA and an absolute increase of 2 ng/mL or more from the nadir was documented and confirmed by a second consecutive value obtained 3 or more weeks later.
Measured: From date of randomization until date of death from any cause, assessed up to 4 years (estimated final OS analysis)
Phase II: Change from Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-C30 (EORTC QLQ-C30) Score
The EORTC QLQ-C30 contains 30 questions assessed by the participant. There are 9 multiple-item scales: 5 scales that assess aspects of functioning (physical, role functioning, cognitive, emotional, and social); 3 symptom scales (Fatigue, Pain, and Nausea and Vomiting); and a global health status/Quality of Life (QOL) scale. There are 5 single-item measures assessing additional symptoms (i.e., dyspnea, loss of appetite, insomnia, constipation, and diarrhea) and a single item concerning perceived financial impact of the disease. All but two questions have 4 point scales ranging from "Not at all" to "Very much." The two questions concerning global health status/ QOL have 7 point scales with ratings ranging from "Very poor" to "Excellent." For each of the 14 domains, final scores are transformed such that they range from 0-100, where higher scores indicate improvement.
Measured: Prior to dosing on Day 1 and every 12 weeks until 1 year after disease progression or early study termination whichever comes first
Phase II: Change from Baseline in European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Prostate Module (EORTC QLQ-PR25) Score
The EORTC QLQ-PR25 is a prostate cancer module for the assessment of health-related quality of life (HRQoL). It consists of 25 questions distributed on 6 domains: urinary symptoms (8 items), incontinence aid (1 item), bowel symptoms (4 items), hormonal treatment-related symptoms (HTRS) (6 items), sexual activity (2 items), and sexual functioning (4 items). Questions use a 4 point scale (1 'Not at all' to 4 'Very much'). All raw domain scores are linearly transformed to a 0-100 scale, with higher scores reflecting either more symptoms (urinary, bowel, hormonal treatment-related symptoms) or higher levels of activity or functioning (sexual).
Measured: Prior to dosing on Day 1 and every 12 weeks until 1 year after disease progression or early study termination whichever comes first
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Apr 2018
- Study start24 May 2018
- Primary completion26 May 2021
- Study completion2 Jun 2022
Why it stopped: Recruitment for PROter A206T-G01-001 (NCT03490838) was halted in Phase I by sponsor decision. Phase II expansion portion of the study was never initiated.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Prostatic NeoplasmStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 27 participants (actual)
Sponsor and investigators
- Lead sponsor
- Advanced Accelerator Applications
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Novartis Pharmaceuticals, Study director, Novartis Pharmaceuticals
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03490838
- Sponsor's protocol ID
- A206T-G01-001
- Other IDs
- 2017-004034-29, CAAA602A12101, 2017
- Acronym
- PROter
- Status last verified
- May 2025
- First submitted
- 26 Mar 2018
- Last updated
- 13 May 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 13 May 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1/2 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
- ClinicalTrials.gov ID
- NCT03490838
- Acronym / sponsor ID
- PROter / A206T-G01-001
- Conditions
- Prostatic Neoplasm
- Keywords
- Genital Neoplasms, Male, Urogenital Neoplasms, Neoplasms by Site, Neoplasms, Prostatic Diseases, Cancer of Prostate, Cancer of the Prostate, Neoplasms, Prostate
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Recruitment for PROter A206T-G01-001 (NCT03490838) was halted in Phase I by sponsor decision. Phase II expansion portion of the study was never initiated.
- Enrolment
- 27 participants (actual)
- Lead sponsor
- Advanced Accelerator ApplicationsIndustry (pharma, biotech, devices)
- Study start
- 24 May 2018 (actual)
- Primary completion
- 26 May 2021 (actual)
- Study completion
- 2 Jun 2022 (actual)
- First posted
- 6 Apr 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
Recruitment for PROter A206T-G01-001 (NCT03490838) was halted in Phase I by sponsor decision. Phase II expansion portion of the study was never initiated. Importantly, this recruitment halt was not a consequence of any safety concern. Ongoing patients at the time of recruitment halt continued per protocol and completed the 1 year safety follow-up prior to early study termination.
The primary objective of the Phase I portion of the study to assess the safety and tolerability of 177Lu-PSMA-R2 and to assess Dose Limiting Toxicities (DLTs) and determine the maximum tolerated dose (MTD) (if reached) and the recommended Phase II dose was not reached due to early recruitment halt.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 6
| Arm | Type | Receives |
|---|---|---|
| Phase I: Dose Escalation Cohort 1 | Experimental | Drug: 177Lu-PSMA-R23.70 GBq (100 mCi) x 3 times |
| Phase I: Dose Escalation Cohort 2 | Experimental | Drug: 177Lu-PSMA-R27.40 GBq (200 mCi) up to 4 times |
| Phase I: Dose Escalation Cohort 3 | Experimental | Drug: 177Lu-PSMA-R211.1 GBq (300 mCi) up to 4 times |
| Phase I: Dose Escalation Cohort 4 | Experimental | Drug: 177Lu-PSMA-R214.8 GBq (400 mCi) up to 4 times |
| Phase I: Dose Escalation Cohort 5 | Experimental | Drug: 177Lu-PSMA-R218.5 GBq (500 mCi) up to 4 times |
| Phase I: Dose Escalation Cohort 6 | Experimental | Drug: 177Lu-PSMA-R218.5 GBq (500 mCi) up to 3 times |
Who may qualify
- Ages
- 18 years and older
- Sex
- Male only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (20 listed)
- Male patients, 18 years of age or older
- Signed and dated written ICF by the patient or legally acceptable representative prior to any study-specific procedures
- Histologically confirmed adenocarcinoma of the prostate
- 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
Key exclusion criteria (20 listed)
- Pathological finding consistent with small cell, neuroendocrine carcinoma of the prostate or any other histology different than adenocarcinoma.
- 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)
- Prior exposure to radioligand therapy radioisotope therapy (e.g. 89Sr), systemic radiotherapy or 223Ra-therapy.
- Current severe urinary incontinence, hydronephrosis, severe voiding dysfunction, any level of urinary obstruction requiring indwelling/condom catheters
- Spinal cord compression or brain metastases
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| 177Lu-PSMA-R2radio-ligand therapy | Drug | Phase I: Dose Escalation Cohort 1, Phase I: Dose Escalation Cohort 2, Phase I: Dose Escalation Cohort 3, Phase I: Dose Escalation Cohort 4, Phase I: Dose Escalation Cohort 5, Phase I: Dose Escalation Cohort 6 |
Primary outcome
Phase I: Incidence of dose limiting toxicities (DLTs) during first cycle of study treatment.
Time frame: Up to 8 weeks after the first 177Lu-PSMA-R2 dose
A dose-limiting toxicity (DLT) is defined as any toxicity not attributable to the disease or disease-related processes under investigation, the time window for DLT assessment period is Cycle 1. To be considered a DLT, it must be related to the IP (attributions: possible, probable, and definite) while fulfilling one of the following criteria as per the NCI Common Toxicity Criteria for Adverse Events (CTCAE) version 5.0.
Phase II: Prostate-Specific Antigen (PSA) response rate 50
Time frame: Week 13 (12 weeks after the first 177Lu-PSMA-R2 injection)
PSA response rate 50 is defined as the proportion of participants who have a greater or equal 50% in PSA from Baseline that is confirmed by a second PSA measurement 4 weeks later, as per Prostate Cancer Working Group 3 (PCWG3) criteria.
19 secondary outcomes
Phase I and II: Treatment Emergent Adverse Event (TEAE) rate
Time frame: From randomization till 30 days safety follow-up, assessed up to 4 years (estimated final OS analysis)
Phase I and II: Objective Response Rate (ORR)
Time frame: From date of randomization assessed up to 4 years (estimated final OS analysis)
Phase I and II: Duration of Response (DoR)
Time frame: From date of randomization until date of progression or date of death from any cause, whichever come first, assessed up to 4 years (estimated final OS analysis)
Phase I and II: Prostate-Specific Antigen (PSA) response rate 30
Time frame: Week 13 (12 weeks after the first 177Lu-PSMA-R2 injection)
Phase I: Prostate-Specific Antigen (PSA) response rate 50
Time frame: Week 13 (12 weeks after the first 177Lu-PSMA-R2 injection)
Phase I: 177Lu-PSMA-R2 plasma concentration
Time frame: Days 1 through 8 post-treatment
Phase I: Maximum plasma concentration (Cmax) of 177Lu-PSMA-R2
Time frame: Day 1 (before the start of infusion, at the mid-point, and just before the end of infusion, then at post infusion at approximately 5, 15, 30 minutes, 1, 2, 4, 6, 8, 24, 40 (+/- 4 hours), 48 hours), Day 4 (+2 days) and Day 8 post end of infusion
Phase I: Minimum plasma concentration (Cmin) of 177Lu-PSMA-R2
Time frame: Day 1 (before the start of infusion, at the mid-point, and just before the end of infusion, then at post infusion at approximately 5, 15, 30 minutes, 1, 2, 4, 6, 8, 24, 40 (+/- 4 hours), 48 hours), Day 4 (+2 days) and Day 8 post end of infusion
Phase I: Area under the plasma concentration-time curve (AUC) of 177Lu-PSMA-R2
Time frame: Day 1 (before the start of infusion, at the mid-point, and just before the end of infusion, then at post infusion at approximately 5, 15, 30 minutes, 1, 2, 4, 6, 8, 24, 40 (+/- 4 hours), 48 hours), Day 4 (+2 days) and Day 8 post end of infusion
Phase I: Dosimetry
Time frame: Days 1 through 8 post-treatment
Phase I and II: Patient Reported Outcomes (PRO) of Mouth Dryness using Xerostomia Questionnaire
Time frame: Prior to dosing on Day 1 and every 12 weeks until 1 year after disease progression or early study termination whichever comes first
Phase I and II: Patient Reported Outcomes (PRO) of Eye Dryness using Xerophthalmia Questionnaire
Time frame: Prior to dosing on Day 1 and every 12 weeks until 1 year after disease progression or early study termination whichever comes first
Phase I and II: Brief Pain Inventory-short Form (PBI-SF)
Time frame: Prior to dosing on Day 1 and every 12 weeks until 1 year after disease progression or early study termination whichever comes first
Phase II: Disease Control Rate (DCR)
Time frame: From date of randomization till 30 days safety fup, assessed up to 4 years (estimated final OS analysis)
Phase II: Radiographic Progression Free Survival (rPFS)
Time frame: From date of randomization until date of radiographic progression or date of death from any cause, whichever comes first, assessed up to 4 years (estimated final OS analysis)
Phase II: Overall Survival (OS)
Time frame: From date of randomization until date of death from any cause, assessed up to 4 years (estimated final OS analysis)
Phase II: Time to Prostate Specific Antigen (PSA) progression
Time frame: From date of randomization until date of death from any cause, assessed up to 4 years (estimated final OS analysis)
Phase II: Change from Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-C30 (EORTC QLQ-C30) Score
Time frame: Prior to dosing on Day 1 and every 12 weeks until 1 year after disease progression or early study termination whichever comes first
Phase II: Change from Baseline in European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Prostate Module (EORTC QLQ-PR25) Score
Time frame: Prior to dosing on Day 1 and every 12 weeks until 1 year after disease progression or early study termination whichever comes first
Results and safety
The study was stopped early (reason given: Recruitment for PROter A206T-G01-001 (NCT03490838) was halted in Phase I by sponsor decision. Phase II expansion portion of the study was never initiated.). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 May 2025.
- Novartis Clinical Trial ResultsLink provided by the sponsor.
- Individual participant dataSharing planned: No
Related trials for Prostatic Neoplasm
Active, not recruiting
Streamlined Geriatric and Oncological Evaluation Based On IC Technology
Breast Cancer, Comorbidities and Coexisting Conditions
Active, not recruitingObservational study
MRI Fusion Biopsy vs. Micro-Ultrasound Guided Biopsy
Prostate Cancer
Enrolling by invitationObservational study
Natural History Study of Early Life Exposures in Agriculture (ELEA)
Prostate Cancer, Leukemia
Not yet recruitingPhase 1/2
STAR0602 With Nivolumab in Non Small Cell Lung Cancer and in Metastatic Castrate-Resistant Prostate Cancer, and STAR0602 Alone in Thymic Carcinoma
NSCLC, Non-Small Cell Lung Cancer
Recruiting
Rehabilitation and Sex Therapy to Optimize Recovery After Prostate Cancer Treatment
Prostate Cancer, Urinary Incontinence
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Novartis Pharmaceuticals study director
Novartis Pharmaceuticals
11 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing 177Lu-PSMA-R2 in people with Prostatic Neoplasm, run by Advanced Accelerator Applications at 11 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 20 inclusion and 20 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 13 May 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 11 sites in United States, Spain. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: Recruitment for PROter A206T-G01-001 (NCT03490838) was halted in Phase I by sponsor decision. Phase II expansion portion of the study was never initiated.). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Phase I: Incidence of dose limiting toxicities (DLTs) during first cycle of study treatment. (time frame: Up to 8 weeks after the first 177Lu-PSMA-R2 dose). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 May 2025.