Description:
The purpose of the initial (phase I) portion of this study is to find a dose level and
administration schedule of the study drug, 225Ac-J591 that can be given without severe side
effects.
Title
- Brief Title: Fractionated and Multiple Dose 225Ac-J591 for Progressive mCRPC
- Official Title: Phase I/II Dose-escalation Study of Fractionated and Multiple Dose 225Ac-J591 for Progressive Metastatic Castration Resistant Prostate Cancer
Clinical Trial IDs
- ORG STUDY ID:
20-01021288
- NCT ID:
NCT04506567
Conditions
Interventions
Drug | Synonyms | Arms |
---|
225Ac-J591 | | Dose- Fractionated Cohort |
225Ac-J591 | | Multiple Dose Cohort |
Purpose
The purpose of the initial (phase I) portion of this study is to find a dose level and
administration schedule of the study drug, 225Ac-J591 that can be given without severe side
effects.
Detailed Description
This clinical trial is for men with progressive metastatic castration resistant prostate
cancer. The purpose of this study is to find the highest dose level of the study drug,
225Ac-J591 that can be given without severe side effects. The research study is being done
because the standard treatments for prostate cancer that has spread beyond the prostate gland
are intended to minimize the adverse effects of the disease. These treatments, however, are
not curative. Patients who choose to participate in this study will have a screening visit to
determine whether or not they are eligible to participate in the study. The treatment phase
is comprised of 8 weeks for the fractionated dose cohort and 8 weeks past last dose of
225Ac-J591 for the multiple dose regimen (for subjects receiving 4 cycles, 26 weeks is
expected). Following treatment, short-term follow up is planned until radiographic
progression, expected to be 6 months.The study medication is called 225Ac-J591, and will be
administered as a single fractionated cycle day 1 and day 15 in the fractionated dose regimen
and as a single dose per cycle repeated every 6 weeks in the multiple dose regimen. Upon
completion of investigational treatment with 225Ac-J591, subjects will undergo
68Ga-PSMA-HBED-CC injection and same day PET/CT/ at the end of study visit to document
treatment response. 68Ga-PSMA-HBED-CC is comprised of gallium-68, which is a PET emitting
radionuclide linked to PSMA-HBED-CC (aka PSMA11), which is a small molecule targeting PSMA.
68Ga-PSMA-HBED-CC will be administered intravenously prior to PET/CT at screening and at
follow up imaging x2. Subsequently survival data and additional treatment(s) information will
be captured from their routine Standard of care (SOC) visits.During the other study visits,
participants will undergo routine tests and procedures, such as physical examinations, and
routine blood tests. Some blood tests will be done for research purposes only. After
completion of therapy, participants may be contacted on a periodic basis to see how they are
doing.
Key eligibility:
- Open to men age 18 and older.
- Diagnosis of progressive metastatic prostate cancer
- Have been previously treated for their disease with particular types of therapy
Trial Arms
Name | Type | Description | Interventions |
---|
Dose- Fractionated Cohort | Experimental | | |
Multiple Dose Cohort | Experimental | | |
Eligibility Criteria
Inclusion Criteria:
1. Histologically or cytologically confirmed adenocarcinoma of prostate
2. 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
3. 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
4. Have previously been treated with at least one of the following in any disease state:
- Androgen receptor signaling inhibitor (such as enzalutamide)
- CYP 17 inhibitor (such as abiraterone acetate)
5. Have previously received taxane chemotherapy (in any disease state), been determined
to be ineligible for taxane chemotherapy by their physician, or refused taxane
chemotherapy.
6. Age > 18 years
7. 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 <3 x ULN in absence of liver metastases; < 5x ULN if due to
liver metastases(in both circumstances bilirubin must meet entry criteria)
8. Ability to understand and the willingness to sign a written informed consent document
Exclusion Criteria
1. Implantation of investigational medical device ≤4 weeks of Treatment Visit 1 (Day 1)
or current enrollment in oncologic investigational drug or device study
2. Use of investigational drugs ≤4 weeks or <5 half-lives of Cycle 1, Day 1 or current
enrollment in investigational oncology drug or device study
3. Prior systemic beta-emitting bone-seeking radioisotopes
4. Known active brain metastases or leptomeningeal disease
5. History of deep vein thrombosis and/or pulmonary embolus within 1 month of C1D1
6. 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
7. Radiation therapy for treatment of PC ≤4 weeks of Day 1 Cycle 1
8. 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
9. 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
10. 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
11. Known history of known myelodysplastic syndrome
Maximum Eligible Age: | 99 Years |
Minimum Eligible Age: | 18 Years |
Eligible Gender: | Male |
Healthy Volunteers: | No |
Primary Outcome Measures
Measure: | Change in the number of subjects with dose limiting toxicity (DLT) |
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 the recommended phase I fractionated dose and multiple dose regimens of 225Ac-J591 dose by utilizing the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. |
Secondary Outcome Measures
Measure: | Change in the number of subjects with radiographic response rate |
Time Frame: | Scans will be performed at screening, day 85 then again at end of study or 100 months |
Safety Issue: | |
Description: | Radiographic response rate by Response evaluation criteria in solid tumors (RECIST) criteria with Prostate Cancer Working Group 3 (PCWG3) modifications |
Measure: | Change in overall survival following fractionated dose and multiple doses of 225Ac-J591 |
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-HBED-CC PET/CT prior to and following investigational treatment |
Time Frame: | Scans will be performed at screening, day 85 and day 168 |
Safety Issue: | |
Description: | |
Measure: | Change in circulating tumor cells (CTC) response |
Time Frame: | Samples will be collected at screening, day 1, day 85 and at disease progression |
Safety Issue: | |
Description: | CTCs will be analyzed through blood specimen collection via CellSearch methodology lab testing |
Measure: | Change in adverse event rate response |
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 |
Details
Phase: | Phase 1/Phase 2 |
Primary Purpose: | Interventional |
Overall Status: | Recruiting |
Lead Sponsor: | Weill Medical College of Cornell University |
Last Updated
November 24, 2020