Prostate Cancer
Conditions
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.
Interventions
DRUG225Ac-J591
225Ac-J591 (13.3 KBq/Kg - 93.3 KBq/Kg or 0.36 uCi/Kg - 2.52 uCi/Kg) on day 1
Sponsors
Prostate Cancer Foundation
United States Department of Defense
National Institutes of Health (NIH)
National Cancer Institute (NCI)
Weill Medical College of Cornell University
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Subjects With Dose Limiting Toxicities (DLT) | Assessed from start of treatment to up to 8 weeks after first study drug administration. | Count of participants will be measured by the recommended phase II dose in utilizing the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 for DLTs. |
| Number of Subjects Who Reached Maximum Tolerated Dose (MTD) | Assessed from start of treatment to up to 8 weeks after first study drug administration. | The MTD is the highest dose amongst the different dose-level cohorts in this study at which no more than 2 (33%) of the subjects in a cohort experience DLT. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Subjects With Prostate Specific Antigen (PSA) Response | PSA was assessed at screening, and up to 6 months after first treatment with study drug. | PSA will be analyzed through blood specimen collection |
| Number of Subjects With Circulating Tumor Cells (CTC) Response | CTC was assessed at screening and 12 weeks after starting study drug. | CTCs will be analyzed through blood specimen collection via CellSearch methodology lab testing |
| Number of Subjects With Radiographic (Imaging) Response | Response were assessed for patients throughout their duration on the study, up to 3 years. | Radiographic response rate by Response evaluation criteria in solid tumors (RECIST) criteria with Prostate Cancer Working Group 3 (PCWG3) modifications |
| Progression Free Survival (PFS) | From the start of treatment to progression, up to 3 years | Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions. |
Countries
United States
Participant flow
Recruitment details
Recruitment took place at at Weill Cornell Medicine New York Presbyterian and Tulane Medical Center.
Participants by arm
| Arm | Count |
|---|---|
| 225Ac-J591 Cohort 1 Cohort 1: Participants were administered of 225Ac-J591 once at the dose level of 13.3 KBq/Kg - 0.36 Ci/Kg via intravenous infusion (IV). Participants were then followed until death for survival assessment | 1 |
| 225Ac-J591 Cohort 2 Cohort 2: Participants were administered of 225Ac-J591 once at the dose level of 26.7 KBq/Kg - 0.72 Ci/Kg via intravenous infusion (IV). Participants were then followed until death for survival assessment. | 1 |
| 225Ac-J591 Cohort 3 Cohort 3: Participants were administered of 225Ac-J591 once at the dose level of 40.0 KBq/Kg - 1.08 Ci/Kg via intravenous infusion (IV). Participants were then followed until death for survival assessment. | 1 |
| 225Ac-J591 Cohort 4 Cohort 4: Participants were administered of 225Ac-J591 once at the dose level of 53.3 KBq/Kg - 1.44 Ci/Kg via intravenous infusion (IV). Participants were then followed until death for survival assessment. | 1 |
| 225Ac-J591 Cohort 5 Cohort 5: Participants were administered of 225Ac-J591 once at the dose level of 66.7 KBq/Kg - 1.80 Ci/Kg via intravenous infusion (IV). Participants were then followed until death for survival assessment. | 6 |
| 225Ac-J591 Cohort 6 Cohort 6: Participants were administered of 225Ac-J591 once at the dose level of 80.0 KBq/Kg - 2.16 Ci/Kg via intravenous infusion (IV). Participants were then followed until death for survival assessment. | 6 |
| 225Ac-J591 Cohort 7 Cohort 7 with Expansion: Participants were administered of 225Ac-J591 once at the dose level of 93.3 KBq/Kg - 2.52 Ci/Kg via intravenous infusion (IV). Participants were then followed until death for survival assessment | 16 |
| Total | 32 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 |
|---|---|---|---|---|---|---|---|---|
| Overall Study | In follow-up | 0 | 0 | 0 | 0 | 0 | 1 | 1 |
| Overall Study | Lost to Follow-up | 0 | 0 | 0 | 0 | 0 | 0 | 1 |
Baseline characteristics
| Characteristic | 225Ac-J591 Cohort 1 | 225Ac-J591 Cohort 2 | 225Ac-J591 Cohort 3 | 225Ac-J591 Cohort 4 | 225Ac-J591 Cohort 5 | 225Ac-J591 Cohort 6 | 225Ac-J591 Cohort 7 | Total |
|---|---|---|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 1 Participants | 1 Participants | 1 Participants | 1 Participants | 5 Participants | 4 Participants | 11 Participants | 24 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 2 Participants | 5 Participants | 8 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 1 Participants | 1 Participants | 1 Participants | 1 Participants | 6 Participants | 6 Participants | 16 Participants | 32 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 1 Participants | 1 Participants | 1 Participants | 1 Participants | 5 Participants | 6 Participants | 15 Participants | 30 Participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 1 Participants | 1 Participants | 1 Participants | 1 Participants | 6 Participants | 6 Participants | 16 Participants | 32 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk |
|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 1 / 1 | 1 / 1 | 1 / 1 | 1 / 1 | 6 / 6 | 6 / 6 | 15 / 16 |
| other Total, other adverse events | 1 / 1 | 1 / 1 | 1 / 1 | 1 / 1 | 6 / 6 | 6 / 6 | 16 / 16 |
| serious Total, serious adverse events | 0 / 1 | 0 / 1 | 0 / 1 | 0 / 1 | 3 / 6 | 2 / 6 | 8 / 16 |
Outcome results
Primary
Number of Subjects Who Reached Maximum Tolerated Dose (MTD)
The MTD is the highest dose amongst the different dose-level cohorts in this study at which no more than 2 (33%) of the subjects in a cohort experience DLT.
Time frame: Assessed from start of treatment to up to 8 weeks after first study drug administration.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| 225Ac-J591 Cohort 1 | Number of Subjects Who Reached Maximum Tolerated Dose (MTD) | 0 Participants |
| 225Ac-J591 Cohort 2 | Number of Subjects Who Reached Maximum Tolerated Dose (MTD) | 0 Participants |
| 225Ac-J591 Cohort 3 | Number of Subjects Who Reached Maximum Tolerated Dose (MTD) | 0 Participants |
| 225Ac-J591 Cohort 4 | Number of Subjects Who Reached Maximum Tolerated Dose (MTD) | 0 Participants |
| 225Ac-J591 Cohort 5 | Number of Subjects Who Reached Maximum Tolerated Dose (MTD) | 0 Participants |
| 225Ac-J591 Cohort 6 | Number of Subjects Who Reached Maximum Tolerated Dose (MTD) | 0 Participants |
| 225Ac-J591 Cohort 7 | Number of Subjects Who Reached Maximum Tolerated Dose (MTD) | 0 Participants |
Primary
Number of Subjects With Dose Limiting Toxicities (DLT)
Count of participants will be measured by the recommended phase II dose in utilizing the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 for DLTs.
Time frame: Assessed from start of treatment to up to 8 weeks after first study drug administration.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| 225Ac-J591 Cohort 1 | Number of Subjects With Dose Limiting Toxicities (DLT) | 0 Participants |
| 225Ac-J591 Cohort 2 | Number of Subjects With Dose Limiting Toxicities (DLT) | 0 Participants |
| 225Ac-J591 Cohort 3 | Number of Subjects With Dose Limiting Toxicities (DLT) | 0 Participants |
| 225Ac-J591 Cohort 4 | Number of Subjects With Dose Limiting Toxicities (DLT) | 0 Participants |
| 225Ac-J591 Cohort 5 | Number of Subjects With Dose Limiting Toxicities (DLT) | 0 Participants |
| 225Ac-J591 Cohort 6 | Number of Subjects With Dose Limiting Toxicities (DLT) | 1 Participants |
| 225Ac-J591 Cohort 7 | Number of Subjects With Dose Limiting Toxicities (DLT) | 0 Participants |
Secondary
Number of Subjects With Circulating Tumor Cells (CTC) Response
CTCs will be analyzed through blood specimen collection via CellSearch methodology lab testing
Time frame: CTC was assessed at screening and 12 weeks after starting study drug.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| 225Ac-J591 Cohort 1 | Number of Subjects With Circulating Tumor Cells (CTC) Response | 1 Participants |
| 225Ac-J591 Cohort 2 | Number of Subjects With Circulating Tumor Cells (CTC) Response | 1 Participants |
| 225Ac-J591 Cohort 3 | Number of Subjects With Circulating Tumor Cells (CTC) Response | 1 Participants |
| 225Ac-J591 Cohort 4 | Number of Subjects With Circulating Tumor Cells (CTC) Response | 1 Participants |
| 225Ac-J591 Cohort 5 | Number of Subjects With Circulating Tumor Cells (CTC) Response | 5 Participants |
| 225Ac-J591 Cohort 6 | Number of Subjects With Circulating Tumor Cells (CTC) Response | 5 Participants |
| 225Ac-J591 Cohort 7 | Number of Subjects With Circulating Tumor Cells (CTC) Response | 8 Participants |
Secondary
Number of Subjects With Prostate Specific Antigen (PSA) Response
PSA will be analyzed through blood specimen collection
Time frame: PSA was assessed at screening, and up to 6 months after first treatment with study drug.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| 225Ac-J591 Cohort 1 | Number of Subjects With Prostate Specific Antigen (PSA) Response | 0 Participants |
| 225Ac-J591 Cohort 2 | Number of Subjects With Prostate Specific Antigen (PSA) Response | 1 Participants |
| 225Ac-J591 Cohort 3 | Number of Subjects With Prostate Specific Antigen (PSA) Response | 1 Participants |
| 225Ac-J591 Cohort 4 | Number of Subjects With Prostate Specific Antigen (PSA) Response | 0 Participants |
| 225Ac-J591 Cohort 5 | Number of Subjects With Prostate Specific Antigen (PSA) Response | 3 Participants |
| 225Ac-J591 Cohort 6 | Number of Subjects With Prostate Specific Antigen (PSA) Response | 3 Participants |
| 225Ac-J591 Cohort 7 | Number of Subjects With Prostate Specific Antigen (PSA) Response | 10 Participants |
Secondary
Number of Subjects With Radiographic (Imaging) Response
Radiographic response rate by Response evaluation criteria in solid tumors (RECIST) criteria with Prostate Cancer Working Group 3 (PCWG3) modifications
Time frame: Response were assessed for patients throughout their duration on the study, up to 3 years.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| 225Ac-J591 Cohort 1 | Number of Subjects With Radiographic (Imaging) Response | 0 Participants |
| 225Ac-J591 Cohort 2 | Number of Subjects With Radiographic (Imaging) Response | 0 Participants |
| 225Ac-J591 Cohort 3 | Number of Subjects With Radiographic (Imaging) Response | 0 Participants |
| 225Ac-J591 Cohort 4 | Number of Subjects With Radiographic (Imaging) Response | 0 Participants |
| 225Ac-J591 Cohort 5 | Number of Subjects With Radiographic (Imaging) Response | 1 Participants |
| 225Ac-J591 Cohort 6 | Number of Subjects With Radiographic (Imaging) Response | 0 Participants |
| 225Ac-J591 Cohort 7 | Number of Subjects With Radiographic (Imaging) Response | 0 Participants |
Secondary
Progression Free Survival (PFS)
Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.
Time frame: From the start of treatment to progression, up to 3 years
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| 225Ac-J591 Cohort 1 | Progression Free Survival (PFS) | 381 Days |
| 225Ac-J591 Cohort 2 | Progression Free Survival (PFS) | 56 Days |
| 225Ac-J591 Cohort 3 | Progression Free Survival (PFS) | 141 Days |
| 225Ac-J591 Cohort 4 | Progression Free Survival (PFS) | 60 Days |
| 225Ac-J591 Cohort 5 | Progression Free Survival (PFS) | 366 Days |
| 225Ac-J591 Cohort 6 | Progression Free Survival (PFS) | 242 Days |
| 225Ac-J591 Cohort 7 | Progression Free Survival (PFS) | 130 Days |