Phase I/II 225Ac-J591 Plus 177Lu-PSMA-I&T for Progressive Metastatic Castration Resistant Prostate Cancer
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. |
ClinicalTrials.gov Identifier: NCT04886986 |
Recruitment Status :
Suspended
(Need to wait until a new collaborator is available and confirmed)
First Posted : May 14, 2021
Last Update Posted : August 21, 2023
|
Tracking Information | |||||||
---|---|---|---|---|---|---|---|
First Submitted Date ICMJE | May 11, 2021 | ||||||
First Posted Date ICMJE | May 14, 2021 | ||||||
Last Update Posted Date | August 21, 2023 | ||||||
Actual Study Start Date ICMJE | June 30, 2021 | ||||||
Estimated Primary Completion Date | December 24, 2024 (Final data collection date for primary outcome measure) | ||||||
Current Primary Outcome Measures ICMJE |
|
||||||
Original Primary Outcome Measures ICMJE | Same as current | ||||||
Change History | |||||||
Current Secondary Outcome Measures ICMJE |
|
||||||
Original Secondary Outcome Measures ICMJE | Same as current | ||||||
Current Other Pre-specified Outcome Measures | Not Provided | ||||||
Original Other Pre-specified Outcome Measures | Not Provided | ||||||
Descriptive Information | |||||||
Brief Title ICMJE | Phase I/II 225Ac-J591 Plus 177Lu-PSMA-I&T for Progressive Metastatic Castration Resistant Prostate Cancer | ||||||
Official Title ICMJE | Phase I/II Study of 225Ac-J591 Plus 177Lu-PSMA-I&T for Progressive Metastatic Castration Resistant Prostate Cancer | ||||||
Brief Summary | This is a phase I/II dose-escalation study of 225Ac-J591 administered together with 177Lu-PSMA-I&T (also known as PNT2002). The two study drugs are 225Ac-J591 and 177Lu-PSMA-I&T. Both drugs are designed to deliver radiation to prostate cancer cells; they are known as radionuclide conjugates (radiation linked to antibodies/molecules that recognize prostate cancer cells). The first phase of the study (phase I) will determine the highest dose of the study drug that can be safely given. The second phase of the study (phase II) will determine the effectiveness of the drug combination in patients with prostate cancer. | ||||||
Detailed Description | This clinical trial is for men with progressive metastatic castration-resistant prostate cancer (mCRPC). The two primary objectives of this trial are to determine the highest dose of 225Ac-J591 and 177Lu-PSMA-I&T that can be administered together (also known as maximum tolerated dose) with the recommended phase II dose and to determine the effectiveness of the drug combination. Patients who choose to participate in this study will have a screening visit to determine whether or not they are eligible for the study. Subject(s) enrollment will be done as 3+3 study design at each dose level. Initially at least 2 subject(s) will be enrolled in Cohort 1 and will receive 225Ac-J591 30 KBq (0.81 µCi) / kg plus 177Lu-PSMA-I&T 6.8 GBq (184 mCi) with dose escalation. The enrollment ceiling of the dose escalation portion of the study is up to 18 treated study participants (up to three groups, up to 6 at each dose level).177Lu-PSMA-I&T will be given at a fixed dose of 6.8 GBq. 225Ac-J591 will be given starting at 30 KBq/kg, with a subsequent dose-escalation by an increment of 5-10 KBq/kg to 40 KBq/kg. The two drugs will be co-administered every 8 weeks, for 2 cycles. Once the recommended phase II dose has been established, the phase II component will enroll up to 24 patients to further test efficacy. Preliminary results of our trials of single-agent 225Ac-J591 (single dose, fractionated dose, multiple dose regimens point towards a dose-response relationship as well as dose-toxicity relationship. In our published trials of 177Lu-J591, a very small difference in administered radioactivity has been associated with large differences in efficacy (PSA response and overall survival) [Tagawa et al. 2013; Tagawa et al. 2019]. In addition, guidance by the FDA recommends more precise testing of radioactivity doses. Therefore, we plan to enroll an additional cohort "1.5" to be treated with 35 KBq/Kg to determine RP2D for this population of patients. The primary efficacy measure will be proportion of patients with PSA decline and proportion of patients with 50%+ PSA decline. Other objectives include to determine the radiographic response rate, biochemical progression-free survival, and overall survival. During the study, patients will be closely monitored for adverse events (side effects); weekly x4 weeks, then every 2 weeks until completion of therapy, then every 4 weeks until patients start another therapy. Long-term follow-up will be every 6 months, for 3 years. During the phase I component, the adverse event assessment phase will be a minimum of 8 weeks after the last dose of 225Ac-J591 and 177Lu-PSMA-I&T. At screening, week 12, and week 24, patients will undergo imaging. Imaging will include 68Ga-PSMA-11 PET/CT. 68Ga-PSMA-11 is comprised of gallium-68, a radiotracer, linked to PSMA-11, a molecule that binds to PSMA. Patients with PSMA-positive tumors are eligible for the study. Additional imaging includes SPECT imaging on day 8 of each cycle, to evaluate radiation uptake into the tumors. |
||||||
Study Type ICMJE | Interventional | ||||||
Study Phase ICMJE | Phase 1 Phase 2 |
||||||
Study Design ICMJE | Allocation: N/A Intervention Model: Single Group Assignment Masking: None (Open Label) Primary Purpose: Treatment |
||||||
Condition ICMJE | Prostate Cancer | ||||||
Intervention ICMJE |
|
||||||
Study Arms ICMJE | Experimental: All Subjects
Patients enrolled in the study will receive the study drugs 225Ac-J591 and 177Lu-PSMA-I&T, along with 68Ga-PSMA-11.
Interventions:
|
||||||
Publications * | Not Provided | ||||||
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline. |
|||||||
Recruitment Information | |||||||
Recruitment Status ICMJE | Suspended | ||||||
Estimated Enrollment ICMJE |
48 | ||||||
Original Estimated Enrollment ICMJE |
33 | ||||||
Estimated Study Completion Date ICMJE | December 27, 2027 | ||||||
Estimated Primary Completion Date | December 24, 2024 (Final data collection date for primary outcome measure) | ||||||
Eligibility Criteria ICMJE | Inclusion Criteria:
Exclusion Criteria:
|
||||||
Sex/Gender ICMJE |
|
||||||
Ages ICMJE | 18 Years to 99 Years (Adult, Older Adult) | ||||||
Accepts Healthy Volunteers ICMJE | No | ||||||
Contacts ICMJE | Contact information is only displayed when the study is recruiting subjects | ||||||
Listed Location Countries ICMJE | United States | ||||||
Removed Location Countries | |||||||
Administrative Information | |||||||
NCT Number ICMJE | NCT04886986 | ||||||
Other Study ID Numbers ICMJE | 20-08022486 | ||||||
Has Data Monitoring Committee | Yes | ||||||
U.S. FDA-regulated Product |
|
||||||
IPD Sharing Statement ICMJE |
|
||||||
Current Responsible Party | Weill Medical College of Cornell University | ||||||
Original Responsible Party | Same as current | ||||||
Current Study Sponsor ICMJE | Weill Medical College of Cornell University | ||||||
Original Study Sponsor ICMJE | Same as current | ||||||
Collaborators ICMJE | Not Provided | ||||||
Investigators ICMJE |
|
||||||
PRS Account | Weill Medical College of Cornell University | ||||||
Verification Date | August 2023 | ||||||
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP |