Trial Title:
Randomized Phase II Trial of Targeted Radiation With no Castration for Mcrpc
NCT ID:
NCT06084338
Condition:
Prostate Cancer
Conditions: Official terms:
Prostatic Neoplasms
Testosterone
Conditions: Keywords:
metastatic castration resistant prostate cancer
mCRPC
SBRT
Metastasis Directed Therapy
Lu177 PSMA
stereotactic body radiotherapy
stereotactic ablative radiotherapy
Pluvicto
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Recruiting
Study design:
Allocation:
Randomized
Intervention model:
Parallel Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Radiation
Intervention name:
stereotactic ablative radiotherapy
Description:
Metastasis directed
Arm group label:
Arm 1
Arm group label:
Arm 2
Other name:
SBRT
Intervention type:
Drug
Intervention name:
Pluvicto
Description:
PSMA targeted radiopharmaceutical therapy
Arm group label:
Arm 1
Arm group label:
Arm 2
Other name:
Lu177-PSMA
Intervention type:
Drug
Intervention name:
topical testosterone
Description:
Topical testosterone 1.62% gel
Arm group label:
Arm 2
Other name:
androgel
Summary:
This trial tests if the combination of comprehensive metastasis directed therapy
delivered by a precision form of external beam radiotherapy (stereotactic ablative
radiotherapy), combined with PSMA targeted radiopharmaceutical therapy and cessation of
castration, and then followed by testosterone replacement, is an effective treatment for
metastatic castration resistant prostate cancer.
All patients will be treated with stereotactic ablative radiotherapy and PSMA targeted
radiopharmaceutical therapy with cessation of castration. Half of patients are randomized
to either receive, or not receive, subsequent testosterone replacement.
Detailed description:
This is a randomized, parallel-arm, two-stage open-label phase 2 study of comprehensive
metastasis directed therapy in the form of stereotactic body radiation therapy (SBRT) to
all detectable sites of disease plus PSMA targeted radiopharmaceutical therapy
(pluvicto), discontinuation of castration, with and without testosterone replacement
therapy (TRT) in metastatic castration resistant prostate cancer (mCRPC).
Criteria for eligibility:
Criteria:
Inclusion Criteria:
- Subject must be 18 years of age or older at the time the Informed Consent is signed
- The subject (or legally acceptable representative if applicable) must provide
written informed consent for the trial
- Pathologic diagnosis of prostate cancer of adenocarcinoma histology; presence small
cell/neuroendocrine carcinoma is exclusionary
- Metastatic disease as documented by:
- Osseous metastases detected by technetium-99m (99mTc) planar bone scan or NaF
PET scan, or CT scan at some point in patient's history
- Soft tissue metastases documented on CT or MRI
- PSMA avid metastatic disease as determined by 18F-DCFPyL: at least one lesion with
PSMA avidity greater than that of liver (see Prescribing Information for Pluvicto)
- Progressive castration resistant prostate cancer as defined by serum testosterone <
50 ng/mL and one of the following:
- PSA progression confirmed per Prostate Cancer Clinical Trials Working Group
(PCWG3)
- Radiographic progression of soft tissues according to Response Evaluation
Criteria in Solid Tumors, version 1.1 (RECIST 1.1) modified based on PCWG3, or
radiographic progression of bone according to PCWG3
- Prior use of a novel AR signaling inhibitor for 4 weeks, including abiraterone
acetate plus prednisone/prednisolone, enzalutamide, apalutamide, and/or darolutamide
NOTE: These AR signaling inhibitors may have been used for mCSPC, M0CRPC, and/or mCRPC.
- ECOG PS grade of 0-2
- 10 metastases detectable on molecular imaging (PSMA and FDG PET) and amenable to
SBRT
- 20% of metastases that are FDG avid but PSMA negative
- Metastases that are not detectable on PSMA and FDG PET do not count toward the
total number of metastases, as they are presumed to represent adequately
treated sites of disease
- Life expectancy 6 months
- Adequate organ function:
- Hemoglobin (hgb) > 8.0 g/dL
- Absolute neutrophil count (ANC) > 1500/ µL
- Platelets > 75,000/ µL
- Total bilirubin 1.5 x ULN OR direct bilirubin ULN for participants with total
bilirubin levels >1.5 x ULN
- ALT and AST 3.0 x ULN ( 5 x ULN for participants with liver metastases)
(Child-Pugh class A and B allowed; Child-Pugh class C is excluded)
- Creatinine < (2.0 mg/dL) during screening evaluation (>2.0 is allowed if EGFR
>30 mL/min/1.73 m2)
- Subject must agree to use contraception during the treatment period plus an
additional 120 days after the last dose of study treatment and must refrain from
donating sperm during this period
Exclusion Criteria:
- Visceral metastases including liver and brain (lung metastases are allowed)
- Small cell/neuroendocrine carcinoma by hematoxylin and eosin light histology
(immunohistochemical detection of rare/occasional cells that stain for
neuroendocrine markers such as synaptophysin, neuron specific enolase, or
chromogranin A is not sufficient to make a diagnosis of small cell/neuroendocrine
carcinoma)
- Anti-neoplastic therapies for prostate cancer must be completed > 2 weeks prior to
Day 1 (initiation of first dose of PSMA RLT)
- Investigational agents must have been completed > 4 weeks of Day 1
Note: Participants must have recovered from all AEs due to previous therapies to Grade 1
or baseline
- Participants with Grade 2 neuropathy may be eligible
- Herbal and non-herbal products that may decrease PSA levels other than medical
castration and megestrol (up to 40 mg/day is allowed) for hot flashes
- Has received prior radiotherapy within 2 weeks of start of study treatment.
Participants must have recovered from all radiation-related toxicities, not
require corticosteroids, and not have had radiation pneumonitis
Note: Participants who have entered the follow-up phase of an investigational study may
participate as long as it has been 4 weeks after the last dose of the previous
investigational agent.
- If a subject has undergone major surgery, they must have recovered adequately from
the toxicities or complications from the intervention within 4 weeks prior to
starting therapy
- History of non-prostate active malignancy requiring treatment in the 24 months prior
to Day 1 except for non-muscle invasive urothelial cancer, non-melanoma skin cancer,
or any cancer that in the opinion of the investigator has been adequately treated
and will not interfere with study procedures or interpretation of results
- Active infection or conditions requiring treatment with antibiotics
- Symptomatic local recurrence in the setting of prior curative intent therapy
(surgery and/or radiation to the prostate)
- Has a history or current evidence of any condition, therapy, or laboratory
abnormality that might confound the results of the study, interfere with the
subject's participation for the full duration of the study, or is not in the best
interest of the subject to participate, in the opinion of the treating investigator
- Has known psychiatric or substance abuse disorders that would interfere with
cooperation with the requirements of the trial
- Subject is planning to conceive or father children within the projected duration of
the study, starting with the screening visit through 120 days after the last dose of
trial treatment
- Current or impending cord compression or another indication for urgent palliative
radiation therapy
Gender:
Male
Gender based:
Yes
Gender description:
Patient must have or have had a prostate
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
Accepts Healthy Volunteers
Locations:
Facility:
Name:
VA Long Beach Healthcare System, Long Beach, CA
Address:
City:
Long Beach
Zip:
90822
Country:
United States
Status:
Not yet recruiting
Contact:
Last name:
Nicholas Nickols, MD
Email:
nicholas.nickols@va.gov
Facility:
Name:
VA Greater Los Angeles Healthcare System, West Los Angeles, CA
Address:
City:
West Los Angeles
Zip:
90073-1003
Country:
United States
Status:
Recruiting
Contact:
Last name:
Nicholas G Nickols, MD PhD
Phone:
(310) 478-3711
Email:
nicholas.nickols@va.gov
Contact backup:
Last name:
Matthew B Rettig, MD
Phone:
(310) 478-3711
Email:
matthew.rettig@va.gov
Investigator:
Last name:
Nicholas George Nickols, MD PhD
Email:
Principal Investigator
Facility:
Name:
Edward Hines Jr. VA Hospital, Hines, IL
Address:
City:
Hines
Zip:
60141-3030
Country:
United States
Status:
Not yet recruiting
Contact:
Last name:
Nicholas Nickols, MD
Email:
nicholas.nickols@va.gov
Start date:
December 14, 2023
Completion date:
December 31, 2028
Lead sponsor:
Agency:
VA Office of Research and Development
Agency class:
U.S. Fed
Source:
VA Office of Research and Development
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06084338
