Description:
This is an open-label, single-center Phase I dose escalation study designed to determine the
dose-limiting toxicity (DLT) and the maximum tolerated dose (MTD) of 225Ac-J591 in a single
dose regimen.
Title
- Brief Title: Phase I Trial of 225Ac-J591 in Patients With mCRPC
- Official Title: Phase I Dose-Escalation Trial of 225Ac-J591 in Patients With Metastatic Castration-Resistant Prostate Cancer
Clinical Trial IDs
- ORG STUDY ID:
1706018281
- SECONDARY ID:
7R01CA207645-03
- NCT ID:
NCT03276572
Conditions
Interventions
Drug | Synonyms | Arms |
---|
225Ac-J591 | 68Ga-PSMA-HBED-CC injection for PET/CT Scan on day 1 and at end of study | All Subjects |
Purpose
This is an open-label, single-center Phase I dose escalation study designed to determine the
dose-limiting toxicity (DLT) and the maximum tolerated dose (MTD) of 225Ac-J591 in a single
dose regimen.
Detailed Description
This clinical trial is for men with advanced 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 visits over
approximately 12 weeks. The study medication is called 225Ac-J591, and participants will
receive an infusion of the study drug on the Treatment visit of the study. Upon completion of
investigational treatment with single dose of 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. 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 |
---|
All Subjects | Experimental | A single dose of 225Ac-J591 will be given to subjects with documented progressive metastatic CRPC. | |
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:
1. PSA progression
2. Objective radiographic progression in soft tissue
3. New bone lesions
3. ECOG performance status of 0-2
4. Have serum testosterone < 50 ng/dL. Subjects must continue primary androgen
deprivation with an LHRH analogue (agonist/antagonist) if they have not undergone
bilateral orchiectomy.
5. Have previously been treated with at least one of the following:
1. Androgen receptor signaling inhibitor (such as enzalutamide)
2. CYP 17 inhibitor (such as abiraterone acetate)
6. Have previously received taxane chemotherapy, been determined to be ineligible for
taxane chemotherapy by their physician, or refused taxane chemotherapy.
7. Age > 18 years
8. Patients must have normal organ and marrow function as defined below:
1. Absolute neutrophil count >2,000 cells/mm3
2. Hemoglobin ≥9 g/dL
3. Platelet count >150,000 x 109/microliter
4. Serum creatinine <1.5 x upper limit of normal (ULN) or calculated creatinine
clearance ≥ 60 mL/min/1.73 m2 by Cockcroft-Gault
5. Serum total bilirubin <1.5 x ULN (unless due to Gilbert's syndrome in which case
direct bilirubin must be normal
6. 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)
9. Ability to understand and the willingness to sign a written informed consent document.
Exclusion Criteria:
1. Implantation of investigational medical device ≤4 weeks of Cycle 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: | N/A |
Minimum Eligible Age: | 18 Years |
Eligible Gender: | Male |
Healthy Volunteers: | No |
Primary Outcome Measures
Measure: | Change in the number of subjects with dose limiting toxicities (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 II dose in utilizing the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. |
Secondary Outcome Measures
Measure: | Change in prostate specific antigen (PSA) response |
Time Frame: | Samples will be collected at Screening, Day 1, Day 8, Day 15, Day 29, Day 57, Day 85 then then every 4 weeks for 3 visits |
Safety Issue: | |
Description: | PSA will be analyzed through blood specimen collection |
Measure: | Change in circulating tumor cells (CTC) response |
Time Frame: | Samples will be collected at Screening, Day 1 and Day 85 visit then every 4 weeks for 3 visits |
Safety Issue: | |
Description: | CTCs will be analyzed through blood specimen collection via CellSearch methodology lab testing |
Measure: | Change in the number of subjects with radiographic (imaging) response |
Time Frame: | Scans will be performed at Screening and Day 85 |
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 the number of subjects in patient reported outcomes (PRO) through Functional Assessment of Cancer Therapy-Prostate (FACT-P) questionnaire |
Time Frame: | Samples will be collected at Screening, Day 1, Day 8, Day 15, Day 29, Day 57, Day 85 then then every 4 weeks for 3 visits |
Safety Issue: | |
Description: | Functional Assessment of Cancer Therapy-Prostate or FACT-P questionnaire is a commonly used patient reported outcome that looks at health-related quality of life in men with prostate cancer. The FACT-p scale is measured from a minimum of 0 (little to no difficulty) to a maximum of 4(very difficult). |
Measure: | Change in the number of subjects in patient reported outcomes(PRO) through Brief Pain Inventory (BPI) short form |
Time Frame: | Samples will be collected at Screening, Day 1, Day 8, Day 15, Day 29, Day 57, Day 85 then then every 4 weeks for 3 visits |
Safety Issue: | |
Description: | BPI is a questionnaire is utilized to assess the severity of pain and the impact it has on daily functioning. The scale is based on a rating of 0-10 |
Measure: | Change in Biochemical and radiographic progression-free survival (PFS) |
Time Frame: | Scans will be captured at Screening and Day 85 then every 4 weeks for 3 visits then every 6 months for 3 years |
Safety Issue: | |
Description: | Radiographic evaluation will include bone scan, CT/MRI of abdomen/pelvis, and Chest x-ray (waived if CT/MRI includes chest). Prostate Cancer Working Group 3(PCWG3) modification will be utilized |
Measure: | Overall survival (OS) following single dose of 225Ac-J591 |
Time Frame: | Survival will be collected from Day1 through study completion up to 100 months |
Safety Issue: | |
Description: | Overall survival will be captured through in-clinic or telephone contact with subjects |
Details
Phase: | Phase 1 |
Primary Purpose: | Interventional |
Overall Status: | Active, not recruiting |
Lead Sponsor: | Weill Medical College of Cornell University |
Last Updated
March 4, 2021