Metastatic Hormone-sensitive Prostate Cancer (mHSPC)
Conditions
Brief summary
This is a prospective, interventional, non-randomized, phase 2 study to assess oncologic outcomes of metastatic hormone-sensitive prostate cancer (mCSPC) patients who receive a risk-adapted treatment approach followed by treatment de-escalation at the Medstar Health network. A pragmatic design will be implemented in order to make the study available to patients at greatest needs from minority populations in the community. Additional assessments include quality-of-life (QoL) and sexual function changes as well as correlative studies. A maximum of 108 patients will be enrolled in this study. The investigators hypothesize that with a risk-adapted treatment approach followed by treatment de-escalation, more than 50% of patients will have radiographic progression-free survival (rPFS) at 36 months. Additionally, the investigators hypothesize that the risk-stratified de-escalation approach will result in fewer treatment-related adverse events and better QoL, compared to historical controls.
Interventions
DRUGAndrogen Deprivation Therapy (ADT)
ADT, Gonadotropin-releasing hormone (GnRH) agonist or antagonists, as prescribed by the treating physician.
DRUGAndrogen Receptor Pathway Inhibitor (ARPI)
Darolutamide is the preferred ARPI for this study; however, patients may receive abiraterone, apalutamide, or enzalutamide at the discretion of their oncologist and based on patient preference.
RADIATIONProstate Radiation
prostate radiation, with or without radiation to metastatic sites
DRUGDocetaxel
Docetaxel will be administered as prescribed by the treating physician.
Sponsors
Georgetown University
Lantheus Medical Imaging
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Adult patients with metastatic castrate sensitive prostate cancer that are eligible for standard of care (SOC) per treating physician. a. Low risk SOC: ADT + ARPI + radiation to the prostate i. For patients with low-risk disease (defined in Section 8.1), prior treatment with ADT or ARPI for up to 8 weeks for mCSPC is permitted; however, prior treatment with docetaxel is not allowed. b. High risk SOC: ADT + ARPI +/- docetaxel i. For patients with high-risk disease (defined in Section 8.1), prior treatment with ADT, ARPI, or docetaxel for up to 8 weeks for mCSPC is permitted. 2. Patients who can give informed consent and are willing to comply with follow-up visits and treatment plans.
Exclusion criteria
1. Patients for whom, in the opinion of the investigator, participation in the study, use of the drugs outlined in the study, or use of the risk-adapted treatment de-escalation strategy is not appropriate or safe. 2. Patients who have received prior treatment with any of the following: 1. Chemotherapy other than docetaxel for prostate cancer any time prior to enrollment; 2. Radiopharmaceuticals for prostate cancer any time prior to enrollment. 3. Patients who have received treatment with radiotherapy (EBRT, brachytherapy, or radiopharmaceuticals) within 2 weeks before prior to the start of study treatment. 4. Patients with prior treatment with an ARPI for non-metastatic disease within 6 months of diagnosis of metastatic disease are not eligible. a. Note: Patients who were diagnosed with metastatic disease or more than 6 months after treatment with an ARPI non-metastatic disease are eligible. 5. Patients who had previous (within 28 days before the start of study drug or 4 half-lives of the investigational treatment of the previous study, whichever is longer) or concomitant participation in another clinical study with investigational medicinal product(s). 6. Patients with an inability to swallow oral medications in the opinion of the clinical investigator. 7. Patients with leptomeningeal disease.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Radiological progression-free survival (rPFS) | 36 months | rPFS is defined as the time from the first dose of systemic therapy for mCSPC to the first documented radiological progression in soft tissue or bone, based on CT, MRI, or NM bone scan, using Response Evaluation Criteria in Solid Tumors v1.1 (RECIST v1.1) for soft-tissue metastases and Prostate Cancer Working Group 3 (PCWG3) criteria for bone metastases, or death from any cause. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall survival (OS) | 5 years | OS is defined as the time from the date of treatment to death from any cause. OS at 5 years is defined as being alive at 5 years after starting of ADT. |
| rPFS using PSMA PET/CT scan combined with PSA response | 5 years | This is defined at the time from the first dose of systemic therapy for mCSPC to the time to progressive disease as measured by PSMA PET/CT scan (RECIP 1.0) combined with PSA response |
| Time to initiation of subsequent antineoplastic therapy | 5 years | Time to initiation of subsequent antineoplastic therapy is defined as the time from initiation of ADT to subsequent antineoplastic therapy for prostate cancer. |
| Disease progression within 5 years of starting ADT for mCSPC | 5 years | The number of patients with disease progression at 5 years |
| Symptomatic skeletal event free (SSE) survival | 5 years | SSE survival is defined as the time from first dose of systemic therapy for mCSPC to the first occurrence of SSE or death from any cause, whichever comes first. An SSE is defined as external beam radiation therapy (EBRT) to relieve skeletal symptoms, or new symptomatic pathologic bone fracture, or occurrence of spinal cord compression or tumor-related orthopedic surgical intervention, whichever comes first. |
| Time to pain progression | 5 years | Time from start date of ADT to the first date a subject experiences a pain progression. Pain will be assessed using the PEG Scale (Pain, Enjoyment, General Activity) Questionnaire |
| Adverse Events | 5 years | Number of patients with an AE that resulted in treatment discontinuation. |
| Quality-of-life changes per Functional Assessment of Cancer Therapy (FACT) Prostate Cancer Symptom Index - 17 (FACT-FPSI-17) | 3 months, 6 months, 9 month, 1 year | Patients with changes to quality of life ans sexual function as measured by National Comprehensive Cancer Network- Functional Assessment of Cancer Therapy (FACT) Prostate Cancer Symptom Index - 17 Item Version (NCCN/FACT-FPSI-17). Score rage 0 to 68, a score of "0" is a severely symptomatic patient and the highest possible score is an asymptomatic patient. |
| Quality-of-life changes per Brief Pain Inventory-Short Form (BPI-SF) | 3 months, 6 months, 9 month, 1 year | Patients with changes to quality of life as measured by Brief Pain Inventory-Short Form (BPI-SF). Score range 0 to 10; a low score equals less pain severity and less pain interference, a higher score equals higher pain severity and interference. |
| Development of osteoporosis | 5 years | The number of patients that develope osteoporosis within 5 years on study |
| Development of osteopenia | 5 years | The number of patients that develope osteopenia within 5 years on study |
| Prevalence of gynecomastia | 5 years | The number of patients who develop Grade 1 to 3 Gynecomastia; |
Countries
United States
Contacts
CONTACTPaul D Leger, MD
PRINCIPAL_INVESTIGATORPaul D Leger, MD
Georgetown University
Outcome results
None listed