Description:
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.
Title
- Brief Title: 225Ac-J591 Plus 177Lu-PSMA-I&T for mCRPC
- Official Title: Phase I/II 225Ac-J591 Plus 177Lu-PSMA-I&T for Progressive Metastatic Castration Resistant Prostate Cancer
Clinical Trial IDs
- ORG STUDY ID:
20-08022486
- NCT ID:
NCT04886986
Conditions
Interventions
Drug | Synonyms | Arms |
---|
225Ac-J591 | | All Subjects |
177Lu-PSMA-I&T | 177Lu-PNT2002 | All Subjects |
68Ga-PSMA-11 | 68Ga-PSMA-HBED-CC | All Subjects |
Purpose
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) 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. The phase I component is a 3+3 dose-escalation design, with
maximum two cohorts. 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 10
KBq/kg to 40 KBq/kg. The two drugs will be co-administered every 8 weeks, for 2 cycles. Once
the maximum tolerated dose has been established, the phase II component will enroll up to 24
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.
Trial Arms
Name | Type | Description | Interventions |
---|
All Subjects | Experimental | Patients enrolled in the study will receive the study drugs 225Ac-J591 and 177Lu-PSMA-I&T, along with 68Ga-PSMA-11. | - 225Ac-J591
- 177Lu-PSMA-I&T
- 68Ga-PSMA-11
|
Eligibility Criteria
Inclusion Criteria:
- 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
- Have serum testosterone < 50 ng/dL. Subjects must continue primary androgen
deprivation with an LHRH/GnRH analogue (agonist/antagonist) if they have not undergone
bilateral 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, Platelet count: >150,000 x
109/uL, 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 in the absence of liver metastases; <3 x ULN if due to
liver metastases (in both circumstances bilirubin must meet entry criteria)
- Ability to understand, and the willingness to sign, a written informed consent
document
Exclusion Criteria:
- Implantation of investigational medical device ≤4 weeks of Treatment visit #1 (Day 1)
or current enrollment in oncologic investigational drug or device study
- Use of investigational drugs ≤4 weeks or <5 half-lives of Treatment visit # 1(Day 1)
or current enrollment in investigational oncology drug or device study
- Prior systemic beta-emitting bone-seeking radioisotopes. Prior radium-223 is allowed
provided at least 90 days have lapsed since last dose
- Prior PSMA-targeted radionuclide therapy (prior PSMA-targeted isotopes used for
imaging/diagnostic purposes are allowed, as is prior PSMA-targeted therapy that does
not involve therapeutic radionuclides)
- Known active brain or leptomeningeal metastases
- History of deep vein thrombosis and/or pulmonary embolus within 1 month of Treatment
visit #1
- 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 PC ≤4 weeks of Treatment visit #1
- 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 at least 140 days 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 myelodysplastic syndrome
Maximum Eligible Age: | 99 Years |
Minimum Eligible Age: | 18 Years |
Eligible Gender: | Male |
Healthy Volunteers: | No |
Primary Outcome Measures
Measure: | 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 |
Safety Issue: | |
Description: | DLTs will be measured by utilizing the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. |
Secondary Outcome Measures
Measure: | Change in biochemical progression-free survival |
Time Frame: | Will be collected at the time of visit 1 through end of study or 100 months |
Safety Issue: | |
Description: | 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. |
Measure: | Change in circulating tumor cells (CTC) count |
Time Frame: | Samples will be collected at screening, week 12, week 24. |
Safety Issue: | |
Description: | CTCs will be analyzed through blood specimen collection via CellSearch methodology lab testing |
Measure: | Number of subjects with radiographic response rate |
Time Frame: | Patients will undergo imaging at screening, week 12, and week 24. |
Safety Issue: | |
Description: | Response evaluation criteria in solid tumors RECIST (Version 1.1) criteria with prostate cancer working group 3 (PCWG3) modifications will be used. |
Measure: | 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. |
Safety Issue: | |
Description: | National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 is used to grade all adverse events |
Measure: | 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 |
Safety Issue: | |
Description: | Overall survival will be captured through in-clinic or telephone contact with subjects |
Measure: | 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. |
Safety Issue: | |
Description: | 68Ga-PSMA-11 PET/CT will be utilized as part of the radiographic assessment. |
Details
Phase: | Phase 1/Phase 2 |
Primary Purpose: | Interventional |
Overall Status: | Recruiting |
Lead Sponsor: | Weill Medical College of Cornell University |
Last Updated
August 18, 2021