Prostate CancerPhase 1/2NCT03042468
Phase I Dose-escalation Study of Fractionated 177Lu-PSMA-617 for Progressive Metastatic CRPC
A Phase 1/2 study testing 177Lu-PSMA-617 and 68Ga-PSMA-HBED-CC in people with Prostate Cancer, run by Weill Medical College of Cornell University at 2 sites in United States.
Trial summary
The purpose of this study is to find the highest dose level of the study drug, 177Lu-PSMA-617 that can be given without severe side effects for advanced prostate cancer. Read more about this study
- Who is it for?
- Ages 18 to 99 years, men only
- Conditions the study is for
- Prostate Cancer
- What is being tested?
- 177Lu-PSMA-617 and 68Ga-PSMA-HBED-CC
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 50 participants
- Where
- 2 sitesUnited States
- Study dates
- Dec 2016to 4 Jun 2026
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 to 99 years
- Men only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Histologically or cytologically confirmed adenocarcinoma of prostate
- Documented progressive metastatic CRPC based on Prostate Cancer Working Group 3 (PCWG3) criteria, which includes at least one of the following criteria:
- PSA progression
- Objective radiographic progression in soft tissue
- New bone lesions
- ECOG performance status of 0-2
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- Have serum testosterone < 50 ng/dL. Subjects must continue primary androgen deprivation with an LHRH/GnRH analogue (agonist/antagonist) if they have not undergone orchiectomy.
- Have previously been treated with at least one of the following:
- Androgen receptor signaling inhibitor (such as enzalutamide)
- CYP 17 inhibitor (such as abiraterone acetate)
- Have previously received taxane chemotherapy, been determined to be ineligible for taxane chemotherapy by their physician, or refused taxane chemotherapy.
- Age > 18 years
- Patients must have normal organ and marrow function as defined below:
- Absolute neutrophil count >2,000 cells/mm3
- Hemoglobin ≥9 g/dL (independent of transfusion and/or growth factors within 1 month prior to registration)
- Platelet count >150,000 x 109/uL (independent of transfusion and/or growth factors within 3 months prior to randomization)
- Serum creatinine <1.5 x upper limit of normal (ULN) or calculated creatinine clearance ≥ 60 mL/min/1.73 m2 by Cockcroft-Gault
- Serum total bilirubin <1.5 x ULN (unless due to Gilbert's syndrome in which case direct bilirubin must be normal
- Serum AST and ALT <1.5 x ULN
- Ability to understand and the willingness to sign a written informed consent document.
Who cannot join
- Use of investigational drugs or implantation of investigational medical device ≤4 weeks of Cycle 1, Day 1 or current enrollment in investigational drug or device study
- Prior systemic beta-emitting bone-seeking radioisotopes
- Brain metastases or leptomeningeal disease
- History of deep vein thrombosis and/or pulmonary embolus within 1 month of study entry
- Other serious illness(es) involving the cardiac, respiratory, CNS, renal, hepatic or hematological organ systems which might preclude completion of this study or interfere with determination of causality of any adverse effects experienced in this study
- Radiation therapy for treatment of PCa ≤4 weeks of Day 1 Cycle 1
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- Patients on stable dose of bisphosphonates or denosumab, which have been started no less than 4 weeks prior to treatment start, may continue on this medication, however patients are not allowed to initiate bisphosphonate/Denosumab therapy during the DLT-assessment period of the study.
- Having partners of childbearing potential and not willing to use a method of birth control deemed acceptable by the principle investigator and chairperson during the study and for 1 month after last study drug administration
- Currently active other malignancy other than non-melanoma skin cancer. Patients are considered not to have "currently active" malignancy if they have completed any necessary therapy and are considered by their physician to be at less than 30% risk of relapse.
- Known history of known myelodysplastic syndrome
Trial locations and contacts
2 sites in 1 country.
United States2 sites
Tulane Cancer Center Clinic
New Orleans, Louisiana, 70112
Weill Cornell Medical College
New York, New York, 10021
About this study
Official title: Phase I/ll Dose-escalation Study of Fractionated Dose 177Lu-PSMA-617 for Progressive Metastatic Castration Resistant Prostate Cancer
The purpose of this study is to find the highest dose level of the study drug, 177Lu-PSMA-617 that can be given without severe side effects for advanced prostate cancer.
Read the detailed description
Phase I dose escalation study with 177Lu-PSMA-617 using dose fractionation regimen will be performed in patients with documented progressive metastatic CRPC. The cumulative 177Lu dose [100 mCi (3.7 GBq) - 600 mCi (22.2 GBq)] will be escalated in up to 6 different dose levels (3 + 3 study design). Additional 10 subjects will be enrolled at the MTD dose level to further assess safety and tolerability and to obtain a preliminary assessment of efficacy. The study will enroll adult males 18 years of age or older with documented progressive metastatic CRPC. The primary objectives are: - To determine the dose limiting toxicity (DLT) of fractionated dose of 177Lu-PSMA-617 - To determine the maximal tolerated and recommended phase II dose of 177Lu-PSMA-617 in a 2-week dose-fractionation regimen Subjects will receive the following study interventions:
- 177Lu-PSMA-617 [50mCi (1.85GBq) - 300mCi (11.1GBq)] intravenous X2 doses, 2 weeks apart (Visit 1 and 2)
- 68Ga-PSMA-HBED-CC [5 ±2mCi or 185 ±74MBq] intravenous during screening and at 12 weeks with standard imaging Subjects will be on this study from screening to end of study (day 85).
The treatment phase comprises of 8 visits over 12 weeks. Patients will be followed until death for survival assessment. Patients removed from study for unacceptable adverse events will be followed until resolution or stabilization of the adverse event. All tests and procedures performed on this study are routine and standard of care except: 68Ga-PSMA-HBED-CC PET/CT scan, administration of investigational agent 177Lu-PSMA-617, research blood samples (CTCs for research, cell-free DNA sample), and PSMA testing on archive tissue.
- Conditions
- Prostate Cancer
- Being tested
- 177Lu-PSMA-617, 68Ga-PSMA-HBED-CC
- Medical subject headings
- Prostatic Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
177Lu-PSMA-617Drug
177Lu-PSMA-617 [50mCi (1.85GBq) - 300mCi (11.1GBq)] intravenous X2 doses, 2 weeks apart (Visit 1 and 2)
68Ga-PSMA-HBED-CCDrug
68Ga-PSMA-HBED-CC [5 ±2mCi or 185 ±74MBq] intravenous during screening and at 12 weeks with standard imaging
| Study group | Role | What they receive |
|---|---|---|
| All subjects | Experimental | 1. 177Lu-PSMA-617 [50mCi (1.85GBq) - 300mCi (11.1GBq)] intravenous X2 doses, 2 weeks apart (Visit 1 and 2)
2. 68Ga-PSMA-HBED-CC [5 ±2mCi or 185 ±74MBq] intravenous during screening and at 12 weeks with standard imaging Receives: Drug: 177Lu-PSMA-617; Drug: 68Ga-PSMA-HBED-CC |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Subjects With Dose Limiting Toxicity (DLT) of Fractionated Dose of 177Lu-PSMA-617
Proportion of subjects experiencing a dose limiting toxicity (DLT) of fractionated dose of 177Lu-PSMA-617 by using 3+3 dose escalation was assessed.
Measured: Assessed throughout the DLT period, up to 92 days after starting study drug.
Number of Subjects That Achieved Cumulative Maximum Tolerated Dose (MTD) Phase II Dose of 177Lu-PSMA-617
This outcome is measuring the number of subjects that achieved MTD. MTD is defined as the highest dose level with an observed incidence of DLT in no more than one out of six patients treated at a particular dose level. If no DLTs were experienced, then a recommended phase II dose was determined in 2-wk dose-fractionation regimen by using a 3+3 dose escalation design, as no MTD was observed.
Measured: from first dose of study drug to at least 12 weeks of subsequent follow-up evaluations, up to 92 days
Recommended Phase II Dose of 177Lu-PSMA-617 in a 2-week Dose-fractionation Regimen
Recommended Phase II dose was determined based on the results of the Phase I portion of the study. Since no Maximum Tolerated Dose was achieved given that no Dose Limiting Toxicities occurred, the Recommended Phase II dose was determined based on the Cohort 5 dose.
Measured: Duration of Phase I, up to 47 months
Secondary outcomes (6)
The Rate of PSA Decline Following Fractionated 177Lu-PSMA-617
Proportion of patients with PSA decline following treatment (fractionated 177Lu-PSMA-617) with the RP2D of fractionated dose 177Lu-PSMA-617 (Phase II). PSA response will be determined by comparing the PSA levels after therapy to the baseline, pre-treatment PSA.
Measured: from baseline visit to short term follow up visit, approximately 6 months
Count of Patients That Had a Radiographic Response Rate Measured by RECIST 1.1 With PCWG3 Modifications
Measured: From start of study to progression of disease with at least 12 weeks of subsequent follow-up evaluations, up to 54 months
Progression-free Survival Measured by PCWG3 (Prostate Cancer Working Group3) Criteria
Progression Free Survival, with progression determined based by Radiographic and Biochemical response. Biochemical response was assessed by comparing the PSA levels after therapy to the baseline, pre-treatment PSA. Declines of ≥ 30% confirmed by a second PSA value ≥2 weeks later, are reported.
Measured: Duration of time on study, from baseline to last follow up visit, up to 54 months
Number of CTC Count Responders
Changes in CTC count as measured by CellSearch and the rate of favorable CTC count and LDH at 12 weeks following fractionated 177Lu-PSMA-617.
All subjects in this study will get blood samples drawn (at screening and EOS visit) for CTC enumeration by CellSearch methodology. Participants whose CTC counts drop to less than 5 or stay below 5 (responders) vs. those who remain at least 5 or above (non-responders) at EOS visit are analyzed.
Measured: Duration of study, from screening to EOS visit, up to 12 weeks
Overall Survival Following Fractionated 177Lu-PSMA-617
Overall survival was defined as the time from start of 177Lu-PSMA-617 to the date of death from any cause, or last date of follow up.
Measured: Up to 5 years
Count of Participants That Experience an Adverse Event
Measured: From screening to end of study visit, up to 54 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Feb 2017 (estimated)
- Study startDec 2016
- Primary completion30 Sep 2021
- Study completion4 Jun 2026
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Prostate CancerStudies of the same condition, open and under way.
- More trials run by Weill Medical College of Cornell UniversityThe sponsor's other registered studies.
- 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 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 50 participants (actual)
Sponsor and investigators
- Lead sponsor
- Weill Medical College of Cornell University
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Scott Tagawa, MD, Principal investigator, Weill Medical College of Cornell University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03042468
- Sponsor's protocol ID
- 1609017542
- Other IDs
- PSMA-617
- Status last verified
- Aug 2026
- First submitted
- 19 Jan 2017
- Last updated
- 14 Sep 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Vlachostergios PJ, Niaz MJ, Skafida M, Mosallaie SA, Thomas C, Christos PJ, Osborne JR, Molina AM, Nanus DM, Bander NH, Tagawa ST. Imaging expression of prostate-specific membrane antigen and response to PSMA-targeted beta-emitting radionuclide therapies in metastatic castration-resistant prostate cancer. Prostate. 2021 Apr;81(5):279-285. doi: 10.1002/pros.24104. Epub 2021 Jan 19.
PubMed 33465252
Study at a glance
From the registry record, last updated by the sponsor on 14 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I/ll Dose-escalation Study of Fractionated Dose 177Lu-PSMA-617 for Progressive Metastatic Castration Resistant Prostate Cancer
- ClinicalTrials.gov ID
- NCT03042468
- Acronym / sponsor ID
- 1609017542
- Conditions
- Prostate Cancer
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 50 participants (actual)
- Lead sponsor
- Weill Medical College of Cornell UniversityUniversity, hospital or other
- Study start
- Dec 2016
- Primary completion
- 30 Sep 2021 (actual)
- Study completion
- 4 Jun 2026 (actual)
- First posted
- 3 Feb 2017 (estimated)
- Results
- Posted 13 Dec 2022
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to find the highest dose level of the study drug, 177Lu-PSMA-617 that can be given without severe side effects for advanced prostate cancer.
Detailed description
Phase I dose escalation study with 177Lu-PSMA-617 using dose fractionation regimen will be performed in patients with documented progressive metastatic CRPC. The cumulative 177Lu dose [100 mCi (3.7 GBq) - 600 mCi (22.2 GBq)] will be escalated in up to 6 different dose levels (3 + 3 study design). Additional 10 subjects will be enrolled at the MTD dose level to further assess safety and tolerability and to obtain a preliminary assessment of efficacy. The study will enroll adult males 18 years of age or older with documented progressive metastatic CRPC. The primary objectives are: - To determine the dose limiting toxicity (DLT) of fractionated dose of 177Lu-PSMA-617 - To determine the maximal tolerated and recommended phase II dose of 177Lu-PSMA-617 in a 2-week dose-fractionation regimen Subjects will receive the following study interventions:
- 177Lu-PSMA-617 [50mCi (1.85GBq) - 300mCi (11.1GBq)] intravenous X2 doses, 2 weeks apart (Visit 1 and 2)
- 68Ga-PSMA-HBED-CC [5 ±2mCi or 185 ±74MBq] intravenous during screening and at 12 weeks with standard imaging Subjects will be on this study from screening to end of study (day 85).
The treatment phase comprises of 8 visits over 12 weeks. Patients will be followed until death for survival assessment. Patients removed from study for unacceptable adverse events will be followed until resolution or stabilization of the adverse event. All tests and procedures performed on this study are routine and standard of care except: 68Ga-PSMA-HBED-CC PET/CT scan, administration of investigational agent 177Lu-PSMA-617, research blood samples (CTCs for research, cell-free DNA sample), and PSMA testing on archive tissue.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| All subjects | Experimental | Drug: 177Lu-PSMA-617, Drug: 68Ga-PSMA-HBED-CC1. 177Lu-PSMA-617 [50mCi (1.85GBq) - 300mCi (11.1GBq)] intravenous X2 doses, 2 weeks apart (Visit 1 and 2) 2. 68Ga-PSMA-HBED-CC [5 ±2mCi or 185 ±74MBq] intravenous during screening and at 12 weeks with standard imaging |
Who may qualify
- Ages
- 18 to 99 years
- Sex
- Male only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (20 listed)
- Histologically or cytologically confirmed adenocarcinoma of prostate
- Documented progressive metastatic CRPC based on Prostate Cancer Working Group 3 (PCWG3) criteria, which includes at least one of the following criteria:
- ECOG performance status of 0-2
- Have serum testosterone < 50 ng/dL. Subjects must continue primary androgen deprivation with an LHRH/GnRH analogue (agonist/antagonist) if they have not undergone orchiectomy.
- Have previously been treated with at least one of the following:
Key exclusion criteria (10 listed)
- Use of investigational drugs or implantation of investigational medical device ≤4 weeks of Cycle 1, Day 1 or current enrollment in investigational drug or device study
- Prior systemic beta-emitting bone-seeking radioisotopes
- Brain metastases or leptomeningeal disease
- History of deep vein thrombosis and/or pulmonary embolus within 1 month of study entry
- Other serious illness(es) involving the cardiac, respiratory, CNS, renal, hepatic or hematological organ systems which might preclude completion of this study or interfere with determination of causality of any adverse effects experienced in this study
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-617177Lu-PSMA-617 [50mCi (1.85GBq) - 300mCi (11.1GBq)] intravenous X2 doses, 2 weeks apart (Visit 1 and 2) | Drug | All subjects |
| 68Ga-PSMA-HBED-CC68Ga-PSMA-HBED-CC [5 ±2mCi or 185 ±74MBq] intravenous during screening and at 12 weeks with standard imaging | Drug | All subjects |
Primary outcome
Number of Subjects With Dose Limiting Toxicity (DLT) of Fractionated Dose of 177Lu-PSMA-617
Time frame: Assessed throughout the DLT period, up to 92 days after starting study drug.
Proportion of subjects experiencing a dose limiting toxicity (DLT) of fractionated dose of 177Lu-PSMA-617 by using 3+3 dose escalation was assessed.
Number of Subjects That Achieved Cumulative Maximum Tolerated Dose (MTD) Phase II Dose of 177Lu-PSMA-617
Time frame: from first dose of study drug to at least 12 weeks of subsequent follow-up evaluations, up to 92 days
This outcome is measuring the number of subjects that achieved MTD. MTD is defined as the highest dose level with an observed incidence of DLT in no more than one out of six patients treated at a particular dose level. If no DLTs were experienced, then a recommended phase II dose was determined in 2-wk dose-fractionation regimen by using a 3+3 dose escalation design, as no MTD was observed.
Recommended Phase II Dose of 177Lu-PSMA-617 in a 2-week Dose-fractionation Regimen
Time frame: Duration of Phase I, up to 47 months
Recommended Phase II dose was determined based on the results of the Phase I portion of the study. Since no Maximum Tolerated Dose was achieved given that no Dose Limiting Toxicities occurred, the Recommended Phase II dose was determined based on the Cohort 5 dose.
6 secondary outcomes
The Rate of PSA Decline Following Fractionated 177Lu-PSMA-617
Time frame: from baseline visit to short term follow up visit, approximately 6 months
Count of Patients That Had a Radiographic Response Rate Measured by RECIST 1.1 With PCWG3 Modifications
Time frame: From start of study to progression of disease with at least 12 weeks of subsequent follow-up evaluations, up to 54 months
Progression-free Survival Measured by PCWG3 (Prostate Cancer Working Group3) Criteria
Time frame: Duration of time on study, from baseline to last follow up visit, up to 54 months
Number of CTC Count Responders
Time frame: Duration of study, from screening to EOS visit, up to 12 weeks
Overall Survival Following Fractionated 177Lu-PSMA-617
Time frame: Up to 5 years
Count of Participants That Experience an Adverse Event
Time frame: From screening to end of study visit, up to 54 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Sep 2026.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 33465252Vlachostergios PJ, Niaz MJ, Skafida M, Mosallaie SA, Thomas C, Christos PJ, Osborne JR, Molina AM, Nanus DM, Bander NH, Tagawa ST. Imaging expression of prostate-specific membrane antigen and response to PSMA-targeted beta-emitting radionuclide therapies in metastatic castration-resistant prostate cancer. Prostate. 2021 Apr;81(5):279-285. doi: 10.1002/pros.24104. Epub 2021 Jan 19.
- Individual participant dataSharing planned: No
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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.
Scott Tagawa, MD principal investigator
Weill Medical College of Cornell University
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing 177Lu-PSMA-617 and 68Ga-PSMA-HBED-CC in people with Prostate Cancer, run by Weill Medical College of Cornell University at 2 sites in United States.
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 10 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: finished, as of the sponsor's last update on 14 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. 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 combined 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.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 13 Dec 2022). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Number of Subjects With Dose Limiting Toxicity (DLT) of Fractionated Dose of 177Lu-PSMA-617 (time frame: Assessed throughout the DLT period, up to 92 days after starting study drug.). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03042468, which also lists 1 linked publication.
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 14 Sep 2026.