ACTInium-J591 Radionuclide Therapy in PSMA-Detected Metastatic HOrmone-Sensitive Recurrent Prostate CaNcer (ACTION)
Primary Purpose
Prostate Cancer Metastatic
Status
Withdrawn
Phase
Phase 1
Locations
Study Type
Interventional
Intervention
Actinium-J591
Stereotactic Body Radiation Therapy
Androgen Deprivation Therapy
Sponsored by
About this trial
This is an interventional treatment trial for Prostate Cancer Metastatic
Eligibility Criteria
Inclusion Criteria:
- Pathologically (histologically or cytologically) proven diagnosis of prostate adenocarcinoma at any anatomical location (for example, prostate, metastatic site), including intraductal or ductal carcinoma, at any time before registration.
- Age ≥ 18 years
- ECOG Performance Status 0-2.
- Prior curative-intent treatment to the prostate, by either:
- External beam and/or brachytherapy to: Prostate alone, prostate and seminal vesicles, prostate and pelvic nodes, or radiation to all three sites.
- Radical prostatectomy alone, radical prostatectomy plus postoperative radiotherapy to the prostate bed, or radical prostatectomy plus postoperative radiotherapy to the pelvic nodes.
- Must meet study entry criteria based on the following diagnostic workup within 120 days prior to enrollment: • History and physical examination
- 99mTc bone scan (Must be negative or equivocal);
- Either CT or MRI of pelvis +/- abdomen (Must be negative or equivocal);
- PSMA PET scan (Must be positive with exception of local disease); Note: All 3 scans are mandatory (bone scan; CT/MR; PET)
- Serum total testosterone >100 ng/dL within 120 days prior to enrollment.
- Be willing to use effective contraception during the entire study period.
- To have adequate organ and marrow function, as defined below:
- a. Absolute neutrophil count (ANC) of ≥2,000/mm3
- b. Hemoglobin ≥9 g/dL without need for transfusion
- c. Platelet count ≥150,000/mm3 and absent history or primary quantitative or qualitative platelet defect
- d. Serum creatinine of ≤1.5 x ULN or calculated creatinine clearance of ≥60 mL/min/1.73 m2 by Cockcroft-Gault (or determined by 24 hour urine collection)
- e. Serum total bilirubin ≤1.5 x ULN (unless due to Gilbert's syndrome, in which case direct bilirubin must be normal)
- f. Serum AST and ALT ≤1.5 x ULN.
Exclusion Criteria:
- 1. Currently on androgen deprivation or anti-androgen therapy.
- Definitive radiologic evidence of metastatic disease on conventional imaging, defined by one of the following:
- a. osseous metastasis on 99mTc radionuclide bone scan, or
- b. extra pelvic nodal/soft tissue disease (> 1.5cm in short axis) on CT or MRI pelvis +/- abdomen
- Spinal cord compression, or spinal intramedullary, brain, and/or visceral (for example liver, lung, etc.) metastasis. Note: Spinal metastases (PSMA PET- detected) with epidural extension are eligible if there is >0.3cm spatial separation between the gross tumor volume and spinal cord.
- Biopsy-proven prostatic carcinoma with signet-ring, sarcomatoid, or neuroendocrine features (for example, small cell).
- Prior metastatic or non-metastatic, invasive malignancy (except non metastatic, non-melanomatous skin cancer) unless continuously disease free for > 3 years.
- Prior chemotherapy for prostate cancer or bilateral orchiectomy. Note: Prior chemotherapy for a different cancer is allowed if continuously disease-free for > 3 years.
- Intrapelvic lymph nodes as only site of prostate cancer recurrence.
- Received a platelet transfusion within 4 weeks of treatment
- Received growth factors for white blood cells or platelets within 4 weeks of treatment
- Prior treatment with unsealed radiation sources such as 89Strontium or 153Samarium-containing compounds (e.g. Metastron, Quadramet)
- History of prior PSMA-TRT
- Known history of myelodysplastic syndrome
- Other serious illness(es) involving the cardiac, respiratory, central nervous, renal, hepatic, or hematological systems which might preclude completion of this study or interfere with determination of causality of any adverse effects experienced in this study.
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm Type
Active Comparator
Active Comparator
Arm Label
Cohort 1
Cohort 2
Arm Description
Outcomes
Primary Outcome Measures
Dose Limiting Toxicity (DLT) Rate
A DLT will is defined as a grade 3 or higher hematologic adverse event or a grade 2 or higher non-hematologic adverse event deemed to be at least possibly related to study treatment. Adverse events will be assessed using CTCAE version 5. Patients will be observed for a DLT for 3 months from the second dose of actinium-J591.
Change in Maximum Tolerated Dose (MTD)
Secondary Outcome Measures
Progression Free Survival (PFS) on conventional Imaging
Progression Free Survival (PFS) on conventional Imaging
Progression Free Survival (PFS) on conventional Imaging
Progression Free Survival (PFS) on conventional Imaging
Progression Free Survival (PFS) on prostate-specific membrane antigen (PSMA) positron emission tomography (PET) imaging.
Progression Free Survival (PFS) on prostate-specific membrane antigen (PSMA) positron emission tomography (PET) imaging.
Progression Free Survival (PFS) on prostate-specific membrane antigen (PSMA) positron emission tomography (PET) imaging.
Progression Free Survival (PFS) on prostate-specific membrane antigen (PSMA) positron emission tomography (PET) imaging.
Changes in PSMA expression measured by comparison of SUV on PSMA PET scans before and after treatment
Change in Percentage of PSA decline
Full Information
NCT ID
NCT05567770
First Posted
October 3, 2022
Last Updated
August 22, 2023
Sponsor
Weill Medical College of Cornell University
Collaborators
Convergent Therapeutics, Inc.
1. Study Identification
Unique Protocol Identification Number
NCT05567770
Brief Title
ACTInium-J591 Radionuclide Therapy in PSMA-Detected Metastatic HOrmone-Sensitive Recurrent Prostate CaNcer
Acronym
ACTION
Official Title
ACTInium-J591 Radionuclide Therapy in PSMA-Detected Metastatic HOrmone-Sensitive Recurrent Prostate CaNcer
Study Type
Interventional
2. Study Status
Record Verification Date
August 2023
Overall Recruitment Status
Withdrawn
Why Stopped
Stakeholder elected not to proceed with the study
Study Start Date
December 2023 (Anticipated)
Primary Completion Date
January 2025 (Anticipated)
Study Completion Date
January 2030 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Weill Medical College of Cornell University
Collaborators
Convergent Therapeutics, Inc.
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
The purpose of this study is to evaluate the safety of combining Actinium- J591 with radiation therapy or with androgen deprivation therapy.
Detailed Description
This is a two cohort pilot study for patients with hormone-sensitive prostate cancer after primary treatment +/- salvage treatment with metastases detected on PSMA-PET scan but equivocal, indeterminate or absent on conventional imaging.
Cohort 1 will have patients with Oligometastatic (low volume, between 1 and 5 metastases) disease and Cohort 2 will have patients with polymetastatic (high volume, ≥5 metastases) disease detected via PSMA PET.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Prostate Cancer Metastatic
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
0 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Cohort 1
Arm Type
Active Comparator
Arm Title
Cohort 2
Arm Type
Active Comparator
Intervention Type
Drug
Intervention Name(s)
Actinium-J591
Intervention Description
Cohort 1 with oligometastatic disease will receive Actinium-J591 and Stereotactic Body Radiation Therapy
Intervention Type
Radiation
Intervention Name(s)
Stereotactic Body Radiation Therapy
Other Intervention Name(s)
SBRT
Intervention Description
Cohort 1 patients with oligometastatic disease will receive Actinium-J591 and Stereotactic Body Radiation Therapy
Intervention Type
Drug
Intervention Name(s)
Androgen Deprivation Therapy
Other Intervention Name(s)
ADT
Intervention Description
Cohort 2 patient with Polymetastatic disease will receive Actinium-J591 and Androgen Deprivation therapy (ADT)
Primary Outcome Measure Information:
Title
Dose Limiting Toxicity (DLT) Rate
Description
A DLT will is defined as a grade 3 or higher hematologic adverse event or a grade 2 or higher non-hematologic adverse event deemed to be at least possibly related to study treatment. Adverse events will be assessed using CTCAE version 5. Patients will be observed for a DLT for 3 months from the second dose of actinium-J591.
Time Frame
24 months
Title
Change in Maximum Tolerated Dose (MTD)
Time Frame
3,6,12,18 and 24 months.
Secondary Outcome Measure Information:
Title
Progression Free Survival (PFS) on conventional Imaging
Time Frame
3 months
Title
Progression Free Survival (PFS) on conventional Imaging
Time Frame
6 months
Title
Progression Free Survival (PFS) on conventional Imaging
Time Frame
12 months
Title
Progression Free Survival (PFS) on conventional Imaging
Time Frame
24 months
Title
Progression Free Survival (PFS) on prostate-specific membrane antigen (PSMA) positron emission tomography (PET) imaging.
Time Frame
3 months
Title
Progression Free Survival (PFS) on prostate-specific membrane antigen (PSMA) positron emission tomography (PET) imaging.
Time Frame
6 months
Title
Progression Free Survival (PFS) on prostate-specific membrane antigen (PSMA) positron emission tomography (PET) imaging.
Time Frame
12 months
Title
Progression Free Survival (PFS) on prostate-specific membrane antigen (PSMA) positron emission tomography (PET) imaging.
Time Frame
24 months
Title
Changes in PSMA expression measured by comparison of SUV on PSMA PET scans before and after treatment
Time Frame
3, 6, 12, and 24 months
Title
Change in Percentage of PSA decline
Time Frame
3, 6, 12, 15, 18, 21, and 24 months.
10. Eligibility
Sex
Male
Gender Based
Yes
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
90 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Pathologically (histologically or cytologically) proven diagnosis of prostate adenocarcinoma at any anatomical location (for example, prostate, metastatic site), including intraductal or ductal carcinoma, at any time before registration.
Age ≥ 18 years
ECOG Performance Status 0-2.
Prior curative-intent treatment to the prostate, by either:
External beam and/or brachytherapy to: Prostate alone, prostate and seminal vesicles, prostate and pelvic nodes, or radiation to all three sites.
Radical prostatectomy alone, radical prostatectomy plus postoperative radiotherapy to the prostate bed, or radical prostatectomy plus postoperative radiotherapy to the pelvic nodes.
Must meet study entry criteria based on the following diagnostic workup within 120 days prior to enrollment: • History and physical examination
99mTc bone scan (Must be negative or equivocal);
Either CT or MRI of pelvis +/- abdomen (Must be negative or equivocal);
PSMA PET scan (Must be positive with exception of local disease); Note: All 3 scans are mandatory (bone scan; CT/MR; PET)
Serum total testosterone >100 ng/dL within 120 days prior to enrollment.
Be willing to use effective contraception during the entire study period.
To have adequate organ and marrow function, as defined below:
a. Absolute neutrophil count (ANC) of ≥2,000/mm3
b. Hemoglobin ≥9 g/dL without need for transfusion
c. Platelet count ≥150,000/mm3 and absent history or primary quantitative or qualitative platelet defect
d. Serum creatinine of ≤1.5 x ULN or calculated creatinine clearance of ≥60 mL/min/1.73 m2 by Cockcroft-Gault (or determined by 24 hour urine collection)
e. Serum total bilirubin ≤1.5 x ULN (unless due to Gilbert's syndrome, in which case direct bilirubin must be normal)
f. Serum AST and ALT ≤1.5 x ULN.
Exclusion Criteria:
1. Currently on androgen deprivation or anti-androgen therapy.
Definitive radiologic evidence of metastatic disease on conventional imaging, defined by one of the following:
a. osseous metastasis on 99mTc radionuclide bone scan, or
b. extra pelvic nodal/soft tissue disease (> 1.5cm in short axis) on CT or MRI pelvis +/- abdomen
Spinal cord compression, or spinal intramedullary, brain, and/or visceral (for example liver, lung, etc.) metastasis. Note: Spinal metastases (PSMA PET- detected) with epidural extension are eligible if there is >0.3cm spatial separation between the gross tumor volume and spinal cord.
Biopsy-proven prostatic carcinoma with signet-ring, sarcomatoid, or neuroendocrine features (for example, small cell).
Prior metastatic or non-metastatic, invasive malignancy (except non metastatic, non-melanomatous skin cancer) unless continuously disease free for > 3 years.
Prior chemotherapy for prostate cancer or bilateral orchiectomy. Note: Prior chemotherapy for a different cancer is allowed if continuously disease-free for > 3 years.
Intrapelvic lymph nodes as only site of prostate cancer recurrence.
Received a platelet transfusion within 4 weeks of treatment
Received growth factors for white blood cells or platelets within 4 weeks of treatment
Prior treatment with unsealed radiation sources such as 89Strontium or 153Samarium-containing compounds (e.g. Metastron, Quadramet)
History of prior PSMA-TRT
Known history of myelodysplastic syndrome
Other serious illness(es) involving the cardiac, respiratory, central nervous, renal, hepatic, or hematological systems which might preclude completion of this study or interfere with determination of causality of any adverse effects experienced in this study.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Himanshu Nagar, M.D.
Organizational Affiliation
Weill Medical College of Cornell University
Official's Role
Principal Investigator
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
ACTInium-J591 Radionuclide Therapy in PSMA-Detected Metastatic HOrmone-Sensitive Recurrent Prostate CaNcer
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