Phase I/II 225Ac-J591 Plus 177Lu-PSMA-I&T for Progressive Metastatic Castration Resistant Prostate Cancer
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|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
|Condition or disease||Intervention/treatment||Phase|
|Prostate Cancer||Drug: 225Ac-J591 Drug: 177Lu-PSMA-I&T Drug: 68Ga-PSMA-11||Phase 1 Phase 2|
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 :||Interventional (Clinical Trial)|
|Estimated Enrollment :||48 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Phase I/II Study of 225Ac-J591 Plus 177Lu-PSMA-I&T for Progressive Metastatic Castration Resistant Prostate Cancer|
|Actual Study Start Date :||June 30, 2021|
|Estimated Primary Completion Date :||December 24, 2024|
|Estimated Study Completion Date :||December 27, 2027|
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.
30 - 40 KBq/kg (dose-escalation) every 8 weeks, for up to 2 cycles. Administered together with 177Lu-PSMA-I&T. Intravenous administration.
6.8 GBq (fixed dose) every 8 weeks, for up to 2 cycles. Administered together with 225Ac-J591. Intravenous administration.
Other Name: 177Lu-PNT2002
[185 ±74 MBq or 5 ±2 mCi] intravenous during screening, 12 weeks, 24 weeks. Imaging agent for PSMA PET/CT.
Other Name: 68Ga-PSMA-HBED-CC
- Proportion of subjects with dose limiting toxicity (DLT) of 225Ac-J591 and 177Lu-PSMA-I&T during dose-escalation phase. [ Time Frame: Will be collected at the time of visit 1 through end of study or 100 months ]DLTs will be measured by utilizing the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.
- Cumulative maximum tolerated dose (MTD) and recommended phase II dose 225Ac-J591 and 177Lu-PSMA I&T [ Time Frame: Will be collected at the time of visit 1 through end of study or 100 months ]The dose that produces an "acceptable" level of toxicity or that, if exceeded, would put subjects at "unacceptable" risk for toxicity. Definition of the MTD usually relies on the sample, as MTD is defined as the dose level at which no more than one patient out of six experienced dose-limiting toxicity (DLT).
- Proportion of PSMA+ subjects (by imaging criteria) with PSA decline following treatment with the combination of 225Ac-J591 and 177Lu-PSMA I&T. [ Time Frame: Will be collected at the time of visit 1 through end of study or 100 months ]Proportion of patients acheiving 50% or greater PSA decline (relative to baseline/pre-treatment PSA). Response may occur at any time following treatment initiation and prior to going off study or initiation of new therapy.
- Change in biochemical progression-free survival [ Time Frame: Will be collected at the time of visit 1 through end of study or 100 months ]PSA progression will be defined as a rise of > 25% above either the pretreatment level or the nadir PSA level (whichever is lowest). PSA must increase by > 2 ng/ml to be considered progression.
- Change in circulating tumor cells (CTC) count [ Time Frame: Samples will be collected at screening, week 12, week 24. ]CTCs will be analyzed through blood specimen collection via CellSearch methodology lab testing
- Number of subjects with radiographic response rate [ Time Frame: Patients will undergo imaging at screening, week 12, and week 24. ]Response evaluation criteria in solid tumors RECIST (Version 1.1) criteria with prostate cancer working group 3 (PCWG3) modifications will be used.
- Safety of treatment and adverse event rate [ Time Frame: Will be collected at the time of visit 1 through end of study or 100 months. ]National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 is used to grade all adverse events
- Overall survival following treatment with 225Ac-J591 and 177Lu-PSMA-I&T [ Time Frame: Survival will be collected from Day 1 through study completion up to 100 months ]Overall survival will be captured through in-clinic or telephone contact with subjects
- Change in disease assessment with 68Ga-PSMA-11 PET/CT prior to and following investigational treatment [ Time Frame: Patients will undergo imaging at screening, week 12, and week 24. ]68Ga-PSMA-11 PET/CT will be utilized as part of the radiographic assessment.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04886986
|United States, New York|
|Brooklyn Methodist Hospital - New York Presbyterian|
|Brooklyn, New York, United States, 11215|
|Weill Cornell Medicine New York Presbyterian|
|New York, New York, United States, 10065|
|Principal Investigator:||Joseph Osborne, MD||Weill Medical College of Cornell University|