STereotActic Body Radiotherapy and 177Lutetium PSMA in Locally Advanced Prostate Cancer
- Conditions
- Malignant Neoplasm of ProstateLocally Advanced Prostate Cancer
- Interventions
- Drug: Lu-PSMA-617Radiation: 5-fraction Stereotactic Body Radiation Therapy (SBRT)
- Registration Number
- NCT06574880
- Lead Sponsor
- Angela Y. Jia, MD PhD
- Brief Summary
The goal of this clinical trial is to is to investigate if it is possible to lower the chance of cancer reoccurrence and also preserve quality of life by using the drug Pluvicto instead of androgen-deprivation therapy to the usual radiation therapy for advanced local prostate cancer.
Participants will receive one dose of Pluvicto, followed by radiation about 6 weeks later. Radiation therapy will be completed in 5 treatments over the period of 2 weeks. A second dose of Pluvicto will be given 6 weeks after radiation is complete. Some participants may also receive a third dose of Pluvicto, and this would be given 6 weeks after the second dose of Pluvicto.
- Detailed Description
Prostate cancer is the most common cancer in men worldwide and second leading cause of cancer death in men. The most common treatment for prostate cancer is radiation therapy (RT) plus long-term androgen deprivation therapy (ADT) for 18-36 months with a consideration for the addition of abiraterone acetate.
With the introduction of abiraterone and other second generation androgen signaling inhibitors (ARSIs) there is great interest in shortening the duration of systemic therapy. This interest stems from the high toxicity rates of ADT and substantial impact on patient-reported quality of life (QoL). The use of ADT is associated with some adverse events. Therefore, the combination of adverse event risks and decrease in quality of life associated with castration have resulted in decreased compliance to long term ADT and even ARSIs, where approximately 50% of patients with locally advanced disease either decline any ADT or stop treatment early. The goal of this clinical trial is to is to investigate if it is possible to lower the chance of cancer reoccurrence and also preserve quality of life by using the drug Pluvicto instead of androgen-deprivation therapy to the usual radiation therapy for advanced local prostate cancer.
This clinical trial will evaluate the safety of using Lu-PSMA-617 with SBRT to the prostate and pelvic lymph nodes, and to determine whether Lu-PSMA-617 can replace androgen deprivation therapy (ADT) to improve oncologic outcomes by use of cytotoxic agents, avoid ADT related side effects, and improve compliance for participants to receive systemic therapy.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- Male
- Target Recruitment
- 45
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Participant must be ≥ 18 years of age.
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ECOG performance status ≤ 1
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Histologic confirmation of prostate adenocarcinoma of the prostate
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PSMA avid disease on PSMA PET/CT, where the tumor in the prostate has SUVmax ≥ 10.
- PSMA PET/CT must be obtained within 4 months.
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Need ≥ 1 criteria:
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Node positive disease on PSMA PET/CT or conventional imaging, as defined by having any of the following:
- Pelvic nodal disease (cN1) as defined by LN stations that commence at the bifurcation of the common iliac vessels
- Regional nodal disease (M1a) as defined by LN stations that commence at the bifurcation of the aorta and bifurcation of the proximal inferior vena cava to the common iliac veins.
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In the absence of nodal metastasis, must have ≥ 2 of the following
- i. cT3a or cT3b by conventional imaging (MRI) or PSMA PET/CT
- ii. Grade group ≥ 4
- iii. PSA ≥ 40 ng/mL
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Adequate organ and marrow function to receive treatment:
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Hemoglobin > 10 g/dL
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White blood cell (WBC) > 3000 / mL
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Absolute neutrophil count ≥ 1,500 / mcL
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Platelets ≥ 100,000 / mcL
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Creatinine ≤ 1.5x ULN
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Estimated glomerular filtration rate (eGFR)* > 50 mL/min
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Total bilirubin** < 2× ULN
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Albumin > 3 g/dL
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Aspartate aminotransferase (AST) < 3× ULN
- *based upon Chronic Kidney Disease- Epidemiology Collaboration (CKD-EPI) equation. Participants with estimated GFR between 50 - 60 mL/min will require a 99mTc-TPA GFR test and only participants with non-obstructive pathology will be included in the study.
- ** Total bilirubin ≤ 2x ULN (except for participants with known Gilbert's Syndrome ≤ 3x ULN is permitted)
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International Prostate Symptoms Score (IPSS) ≤ 15.
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Medically fit for treatment and agreeable to follow-up.
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Ability to understand and the willingness to sign a written informed consent.
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Participants with partners of childbearing potential, agreement to use barrier contraceptive method (condom) and to continue its use for 14 weeks from receiving the last dose of Lu-PSMA-617. Participants must also not donate sperm for 14 weeks from receiving the last dose of Lu-PSMA-617.
- Clinical or radiographic evidence of distant metastatic disease (M1a above aortic bifurcation, M1b, or M1c) by any imaging. Participants are allowed to M1a nodal disease that is below the aortic bifurcation. Negative PSMA PET/CT is an acceptable substitute to conventional staging.
- Prostate gland size >90 cc measured by ultrasound or MRI
- Prior head and neck radiation therapy.
- Prior treatment for prostate cancer (incudes chemotherapy, radiation therapy, or anti-androgen therapy).
- Prohibited within 30 days prior to administration to study treatment: spironolactone and other investigational drug therapies.
- Prohibited 3 months before participant registration and during administration of study treatment: oral ketoconazole, chemotherapy, immunotherapy, estrogens, and radiopharmaceuticals.
- History of prior pelvic radiation therapy.
- Enrollment concurrently in another investigational drug study within 6 months of registration.
- History of another active malignancy within the previous 3 years except for adequately treated skin cancer or superficial bladder cancer.
- History of prior hematologic malignancies, including myelodysplastic syndrome or leukemia.
- History of or active Crohn's disease or ulcerative colitis.
- Contraindication to or inability to tolerate PSMA/PET.
- Any condition that in the opinion of the investigator would preclude participation in this study.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Lu-PSMA-617 + SBRT Lu-PSMA-617 * Lu-PSMA-617: 7.4GBq intravenous infusion once with cycle 1, followed by 7.4GBq cycle 2 that is delivered 6 weeks after SBRT , and potentially 7.4GBq cycle #3 delivered 6 weeks after cycle #2 pending dose escalation * Radiation therapy: 5 fractions to prostate and elective nodal irradiation, SBRT, delivered 6 weeks after cycle 1 of 177Lu-PSMA-617 Lu-PSMA-617 + SBRT 5-fraction Stereotactic Body Radiation Therapy (SBRT) * Lu-PSMA-617: 7.4GBq intravenous infusion once with cycle 1, followed by 7.4GBq cycle 2 that is delivered 6 weeks after SBRT , and potentially 7.4GBq cycle #3 delivered 6 weeks after cycle #2 pending dose escalation * Radiation therapy: 5 fractions to prostate and elective nodal irradiation, SBRT, delivered 6 weeks after cycle 1 of 177Lu-PSMA-617
- Primary Outcome Measures
Name Time Method Phase II: Androgen deprivation therapy (ADT)-free survival 3 years post treatment The Phase II goal is to determine the 3-year rate of ADT-free survival.
Phase I: Maximum tolerated dose (MTD) of Lu-PSMA-617 4 weeks after final dose of treatment (treatment expected to last up to six months) The Phase I goal is to determine the maximally tolerated dose (MTD) of Lu-PSMA-617 when administered with prostate SBRT treatment. The MTD will be captured by analyzing the incidence of dose limiting toxicities occurring within the four weeks after the last dose of treatment.
- Secondary Outcome Measures
Name Time Method Prostate Cancer-specific Survival (PCSM) 5 years post treatment Prostate cancer specific mortality (PCSM) is defined the time from Day 1 to death directly attributable to prostate cancer, death from treatment complications, or death from unknown causes in participants with active prostate cancer or previously documented clinical or biochemical relapse.
PSA Progression Free Survival 2 years post treatment PSA progression-free survival will be analyzed at 24 months post last dose of treatment.
Overall Survival (OS) 5 years post treatment Overall Survival (OS) is defined as the time from Day 1 until death due to any cause. For subjects who do not die, time to death will be censored at the time of last contact.
Cumulative incidence of distant metastases 5 years post treatment Distant metastases (DM) is defined as the time from Day 1 until development of distant metastases on CT, MRI, bone scan or PSMA PET, or death from prostate cancer.
Change in Quality of life score as measured by EPIC-26 Baseline to 5 years post treatment EPIC-26 is a short form version of the full Expanded Prostate Cancer Index Composite (EPIC). This version contains 26 items and the same 5 domains as the full version of EPIC: urinary incontinence, urinary irritative/obstructive, bowel, sexual, and hormonal. Response options for each EPIC item for a Likert scale, and multi-item scare scores are transported linearly to a 0-100 scale with higher scores representing better QoL. The time frame asked in the question relates to symptoms experienced within the prior 4 weeks.
Change in Quality of life score as measured by XeQoLS Baseline to 5 years post treatment Xerostomia-related Quality of Life Questionnaire (XeQoLS) is a questionnaire used to measure how dry mouth and salivary dysfunction affect participants' quality of life (QoL). This questionnaire consists of 15 questions across four major domains: physical functioning, personal/psychological functioning, social functioning, and pain/discomfort issues. The XeQoLS is a self-administered tool, and participants are asked to rate each symptom on a 5-point Likert scale from 0 to 4, with higher scores indicating increased xerostomia burden. An average of scores in each domain is calculated, and the average score ranges from 0 to 4. A total score is calculated as an average of the scores from each of the domain.
Change in Quality of life score as measured by FACT-RNT Baseline to 5 years post treatment FACT-RNT is a patient-reported outcomes (PRO) measure for PCa participants receiving radionuclide therapy. It has not yet been validated in a prospective manner. It consists of 15 questions on a 5-point Likert scale, in a recall period of the past 7 days. Each item score is added, and the sum is linearly transformed to produce the final summary score ranging from 0 to 100, with higher scores representing better QoL.
Time-to-castration-resistant prostate cancer 5 years post treatment To determine the average time-to-castration-resistant prostate cancer.
Rate of participants with post treatment PSA in goal range 12 weeks post treatment Rate of obtaining a post-treatment PSA of ≤ 0.5 ng/mL following treatment with 177Lu-PSMA-617 and prostate and nodal SBRT.
Biochemical recurrence (BCR) 5 years post treatment To determine the rate of biochemical recurrence (BCR), defined as PSA nadir + 2 ng/mL.
Time to any salvage therapy 5 years post treatment The time to any salvage therapy, or Time-to-next-intervention (TTNI), is defined as is defined as the time from Day 1 to the time of initiation of any additional (i.e., outside of planned protocol treatment) cancer-directed therapy, including but not limited to androgen deprivation, other systemic prostate cancer therapeutics, palliative radiotherapy, or surgical intervention specifically addressing complications of metastases. In the absence of a defining event, TTNI will be censored at the date of last visit documenting absence of interventions.
Incidence of acute toxicity 5 years post treatment The goal is to describe acute toxicity following treatment with Lu-PSMA-617 and prostate and nodal SBRT.
Incidence of late toxicity 5 years post treatment The goal is to describe late treatment toxicity following treatment with Lu-PSMA-617 and prostate and nodal SBRT.
Proportion of participants with PSA50-RR 12 weeks post treatment The proportion of participants with PSA50-RR at 12 weeks post all treatment will be summarized with 95% confidence interval (CI), where PSA50-RR is defined as the proportion of men with a PSA reduction of at least 50% at 6 weeks after the last 177Lu-PSMA-617 treatment, compared with baseline PSA prior to 177Lu-PSMA-617 treatment.
Trial Locations
- Locations (1)
University Hospitals Cleveland Medical Center Seidman Cancer Center, Case Comprehensive Cancer Center
🇺🇸Cleveland, Ohio, United States