Phase I Trial of 225Ac-J591 in Patients With mCRPC
Study Details
Study Description
Brief Summary
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 1 |
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:
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Open to men age 18 and older.
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Diagnosis of progressive metastatic prostate cancer
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Have been previously treated for their disease with particular types of therapy.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: All Subjects A single dose of 225Ac-J591 will be given to subjects with documented progressive metastatic CRPC. |
Drug: 225Ac-J591
225Ac-J591 (13.3 KBq/Kg - 93.3 KBq/Kg or 0.36 uCi/Kg - 2.52 uCi/Kg) on day 1
Other Names:
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Outcome Measures
Primary Outcome Measures
- Change in the number of subjects with dose limiting toxicities (DLT) [Will be collected at the time of visit 1 through end of study or 100 months]
DLTs will be measured by the recommended phase II dose in utilizing the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.
- Maximum tolerated dose (MTD) [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 two patients out of six experienced dose-limiting toxicity (DLT).
Secondary Outcome Measures
- Change in prostate specific antigen (PSA) response [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]
PSA will be analyzed through blood specimen collection
- Change in circulating tumor cells (CTC) response [Samples will be collected at Screening, Day 1 and Day 85 visit then every 4 weeks for 3 visits]
CTCs will be analyzed through blood specimen collection via CellSearch methodology lab testing
- Change in the number of subjects with radiographic (imaging) response [Scans will be performed at Screening and Day 85]
Radiographic response rate by Response evaluation criteria in solid tumors (RECIST) criteria with Prostate Cancer Working Group 3 (PCWG3) modifications
- Change in the number of subjects in patient reported outcomes (PRO) through Functional Assessment of Cancer Therapy-Prostate (FACT-P) questionnaire [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]
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).
- Change in the number of subjects in patient reported outcomes(PRO) through Brief Pain Inventory (BPI) short form [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]
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
- Change in Biochemical and radiographic progression-free survival (PFS) [Scans will be captured at Screening and Day 85 then every 4 weeks for 3 visits then every 6 months for 3 years]
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
- Overall survival (OS) following single dose of 225Ac-J591 [Survival will be collected from Day1 through study completion up to 100 months]
Overall survival will be captured through in-clinic or telephone contact with subjects
Eligibility Criteria
Criteria
Inclusion Criteria:
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Histologically or cytologically confirmed adenocarcinoma of prostate
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Documented progressive metastatic CRPC based on Prostate Cancer Working Group 3 (PCWG3) criteria, which includes at least one of the following criteria:
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PSA progression
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Objective radiographic progression in soft tissue
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New bone lesions
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ECOG performance status of 0-2
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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.
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Have previously been treated with at least one of the following:
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Androgen receptor signaling inhibitor (such as enzalutamide)
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CYP 17 inhibitor (such as abiraterone acetate)
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Have previously received taxane chemotherapy, been determined to be ineligible for taxane chemotherapy by their physician, or refused taxane chemotherapy.
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Age > 18 years
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Patients must have normal organ and marrow function as defined below:
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Absolute neutrophil count >2,000 cells/mm3
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Hemoglobin ≥9 g/dL
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Platelet count >150,000 x 109/microliter
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Serum creatinine <1.5 x upper limit of normal (ULN) or calculated creatinine clearance ≥ 60 mL/min/1.73 m2 by Cockcroft-Gault
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Serum total bilirubin <1.5 x ULN (unless due to Gilbert's syndrome in which case direct bilirubin must be normal
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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)
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Ability to understand and the willingness to sign a written informed consent document.
Exclusion Criteria:
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Implantation of investigational medical device ≤4 weeks of Cycle 1, Day 1 or current enrollment in oncologic investigational drug or device study
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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
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Prior systemic beta-emitting bone-seeking radioisotopes
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Known active brain metastases or leptomeningeal disease
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History of deep vein thrombosis and/or pulmonary embolus within 1 month of C1D1
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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
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Radiation therapy for treatment of PC ≤4 weeks of Day 1 Cycle 1
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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.
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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
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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.
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Known history of known myelodysplastic syndrome
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Tulane Cancer Center Clinic | New Orleans | Louisiana | United States | 70112 |
| 2 | Weill Cornell Medical College | New York | New York | United States | 10065 |
Sponsors and Collaborators
- Weill Medical College of Cornell University
- Prostate Cancer Foundation
- United States Department of Defense
- National Institutes of Health (NIH)
- National Cancer Institute (NCI)
Investigators
- Principal Investigator: Scott Tagawa, MD, Weill Medical College of Cornell University
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- 1706018281
- 7R01CA207645-03