Clinical trial NCT03276572: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Prostate Cancer
Lead sponsor: Weill Medical College of Cornell University
Sponsor class: OTHER
Collaborators: name: Prostate Cancer Foundation
name: United States Department of Defense
name: National Institutes of Health (NIH)
name: National Cancer Institute (NCI)
First posted: 2017-09-08
Enrollment: 32
Sex: MALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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.

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

Primary outcomes:
measure: Number of Subjects With Dose Limiting Toxicities (DLT)
timeFrame: Assessed from start of treatment to up to 8 weeks after first study drug administration.
measure: Number of Subjects Who Reached Maximum Tolerated Dose (MTD)
timeFrame: Assessed from start of treatment to up to 8 weeks after first study drug administration.
Secondary outcomes:
measure: Number of Subjects With Prostate Specific Antigen (PSA) Response
timeFrame: PSA was assessed at screening, and up to 6 months after first treatment with study drug.
measure: Number of Subjects With Circulating Tumor Cells (CTC) Response
timeFrame: CTC was assessed at screening and 12 weeks after starting study drug.
measure: Number of Subjects With Radiographic (Imaging) Response
timeFrame: Response were assessed for patients throughout their duration on the study, up to 3 years.
measure: Progression Free Survival (PFS)
timeFrame: From the start of treatment to progression, up to 3 years
Other outcomes:
Locations:
city: New Orleans
country: United States
facility: Tulane Cancer Center Clinic
state: Louisiana
city: New York
country: United States
facility: Weill Cornell Medical College
state: New York
Study officials:
affiliation: Weill Medical College of Cornell University
name: Scott Tagawa, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Vlachostergios PJ, Niaz MJ, Skafida M, Mosallaie SA, Thomas C, Christos PJ, Osborne JR, Molina AM, Nanus DM, Bander NH, Tagawa ST. Imaging expression of prostate-specific membrane antigen and response to PSMA-targeted beta-emitting radionuclide therapies in metastatic castration-resistant prostate cancer. Prostate. 2021 Apr;81(5):279-285. doi: 10.1002/pros.24104. Epub 2021 Jan 19.