This research is being done to find out if the study drug, 177Lu-PSMA-617, given before and during standard of care External Beam Radiation Therapy (EBRT) treatment, with a shorter course of Androgen Deprivation Therapy (ADT) (6 months) is (1) safe and effective compared to standard of care alone, and (2) can reduce the side effects caused by long-term (24 months) ADT in men with high risk localized prostate cancer.
Men with high-risk localized prostate cancer include those with stage cT3a or Grade Group 4/5 or Prostate Specific Antigen (PSA) \>20 ng/mL, and the proportional rate of high-risk disease has increased to 20% of newly diagnosed patients in the US. These patients are currently recommended treatment with a combination of definitive radiotherapy and long-term androgen deprivation therapy (NCCN category 1) or radical prostatectomy with pelvic lymph node dissection. Radiotherapy most often consists of external-beam radiotherapy (EBRT) in 28 to 45 daily fractions with 1.5 to 3 years of ADT. Multiple phase III studies have shown a benefit in survival with long-term ADT. However, given the toxicities of long-term ADT, including fatigue, mood changes, sexual dysfunction, osteopenia, weight gain, diabetes and cardiovascular disease, many patients are reluctant to complete long-term ADT. This leads to significant demand for investigation of lower-toxicity alternatives to long-term ADT for patients with high-risk localized prostate cancer. The combination of 177Lu-PSMA-617 with definitive EBRT and 6 months ADT for high-risk prostate cancer has the potential to increase the cumulative absorbed dose to the prostate, involved nodes, and micrometastatic disease, as well as decrease toxicity and improve QoL compared with EBRT and long-term ADT. ADT has been shown to increase radiosensitivity and PSMA expression of prostate cancer; therefore 6 months of ADT was selected to optimize the combination therapy while avoiding toxicities associated with long-term ADT. There are significant unknowns with respect to absorbed dose and toxicities of this potential combination of 177Lu-PSMA-617 and EBRT. In addition, the relative efficacy compared to EBRT plus long-term ADT is unknown. The investigators therefore propose a phase II randomized study of dosimetry, safety, and efficacy of Lu-177-PSMA-617, EBRT, and short-term ADT (6 months) in comparison with EBRT and long-term ADT (24 months).
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
60
In Arm A, 177Lu-PSMA-617 will be given as intravenous infusion every 6 weeks, up to 4 cycles. Cycle 1 Day 1 (C1D1) of 177Lu-PSMA-617 will start at least 2 weeks after ADT, and EBRT will start at least 2 weeks after C1D1.
In Arm B, EBRT will start 3-7 weeks after Day 1 of ADT.
Johns Hopkins University
Baltimore, Maryland, United States
RECRUITINGRate of testosterone recovery (TR)
The rate of testosterone recovery (TR) will be determined by the percentage of patients who recover normal T levels within 3 years after randomization.
Time frame: Post randomization up to 3 years.
Biochemical disease-free survival (BC-DFS)
Measured from randomization to the time of a measured PSA value at least 2 ng/mL above nadir, and at least 25% above nadir, or death, whichever occurs first.
Time frame: From randomization up to 3 years.
Time-to-Next-Intervention (TTNI)
TTNI is defined as the period of time from randomization to the initiation of any additional cancer-directed therapy. In the absence of a defining event, TTNI will be censored at the date of last visit documenting absence of interventions.
Time frame: From randomization up to 3 years.
ADT-free survival (ADT-FS)
ADT-free survival defined as the time from randomization to the time of initiation of palliative ADT or death, whichever occurs first.
Time frame: From randomization up to 3 years.
Metastasis-free survival (MFS)
MFS is defined as the time from randomization to the time of detection of at least one new metastatic lesions on conventional imaging. Patients who do not develop at least one new metastasis will be censored at the time of the last disease assessment.
Time frame: From randomization up to 3 years.
Overall Survival (OS)
For subjects who do not die, time to death will be censored at the time of last contact.
Time frame: From randomization to the date of death, up to 3 years.
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.
Toxicity as assessed by adverse events
Toxicity of combination therapy with EBRT + 6 mo ADT + 177Lu-PSMA-617 by collecting CTCAE v5.0 adverse events.
Time frame: In Arm A, AEs assessed 7-10 days prior to every cycle of 177Lu-PSMA-617. In Arm B, AEs assessed at baseline, Day 1, EOT, and after the completion of EBRT. For both arms, starting at 6 months, AEs assessed every 6 months up to 5 years (no Month 54 f/u).
Quality of Life as assessed by Expanded Prostate Index Composite (EPIC)
Score range, 0-100. Higher score better quality of life.
Time frame: Pre-treatment, end of RT, 6 months, and every 6 months thereafter up to 5 years (no Month 54 f/u).
Quality of Life as assessed by European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ) Core 30
Score range from 0 to 100. A higher score indicates better quality of life.
Time frame: Pre-treatment, end of RT, 6 months, and every 6 months thereafter up to 5 years (no Month 54 f/u).
Quality of Life as assessed by Xerostomia Quality of Life Scale (XeQoLS)
Score range 0 to 60, with higher scores indicating worse quality of life.
Time frame: Pre-treatment, end of RT, 6 months, and every 6 months thereafter up to 5 years (no Month 54 f/u).
Correlation of Toxicities and Absorbed Dose
To correlate rate of CTCAE v5.0 grade 3 toxicities with mean absorbed dose to normal organs at risk. Specifically, pelvic organ toxicities will be correlated with mean EBRT dose, mean Lu-PSMA absorbed dose and mean cumulative absorbed dose for the bladder, rectum, and bowel.
Time frame: In Arm A, AEs assessed 7-10 days prior to every cycle of 177Lu-PSMA-617. In Arm B, AEs assessed at baseline, Day 1, EOT, and after the completion of EBRT. For both arms, starting at 6 months, AEs assessed every 6 months up to 5 years (no Month 54 f/u).