Castration-Sensitive Prostate Adenocarcinoma, Metastatic Castration-Sensitive Prostate Adenocarcinoma, Stage IVB Prostate Cancer AJCC v8
Conditions
Brief summary
This phase II trial compares giving estrogen with an androgen receptor signaling inhibitor to standard of care luteinizing hormone-releasing hormone (LHRH) analogues with an androgen receptor signaling inhibitor for improving quality of life for patients with hormone sensitive prostate cancer that is newly diagnosed or that has come back after a period of improvement (recurrent) and has spread from where it first started (primary site) to other places in the body (metastatic). Standard prostate cancer treatment decreases hormone levels, specifically estrogen, in the body which can lead to hot flashes, fatigue, decreased bone health, and cardiovascular and metabolic dysfunction. Transdermal estrogen may help to alleviate these symptoms. Androgen receptor signaling inhibitors work by blocking the effects of androgen (a male reproductive hormone) to stop the growth and spread of tumor cells. LHRH analogues are a type of androgen deprivation therapy that blocks the use of androgen by the tumor cells. Giving estrogen with androgen receptor signaling inhibitor may improve quality of life in men with newly diagnosed or recurrent metastatic hormone sensitive prostate cancer.
Detailed description
OUTLINE: Patients are randomized to 1 of 2 cohorts. COHORT 1: Patients receive standard of care LHRH agonist or LHRH antagonist according to the Food and Drug Administration approved dose and schedule in the absence of disease progression or unacceptable toxicity. Starting 4 weeks after initiation of LHRH agonist/antagonist, patients also receive ARSI per physician's choice for a minimum of 12 weeks in the absence of disease progression or unacceptable toxicity. Patients with a median daily hot flash score ≥ 6 after 12 weeks of therapy may crossover to cohort 2. Patients undergo computed tomography (CT) scan or magnetic resonance imaging (MRI), bone scan, dual x-ray absorptiometry (DEXA) scan and blood sample collection throughout the study. COHORT 2: Patients receive estrogen via transdermal patch on days 1, 4, 8, 12, 16, 20, 24 and 28 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Starting 4 weeks after initiation of transdermal estrogen, patients also receive ARSI per physician's choice for a minimum of 12 weeks in the absence of disease progression or unacceptable toxicity. Patients undergo CT scan or MRI, bone scan, DEXA scan and blood sample collection throughout the study. After completion of study treatment, patients are followed up at 30 days and every 6 months for 2 years.
Interventions
DRUGAndrogen Receptor Pathway Inhibitor
Given per standard of care
Given via transdermal patch
PROCEDUREBone Scan
Undergo bone scan
PROCEDUREComputed Tomography
Undergo CT scan
PROCEDUREDual X-ray Absorptiometry
Undergo DEXA scan
BIOLOGICALGonadotropin-releasing Hormone Analog
Given per standard of care
PROCEDUREMagnetic Resonance Imaging
Undergo MRI
OTHERSurvey Administration
Ancillary studies
PROCEDUREBiospecimen Collection
Undergo blood sample collection
Sponsors
University of Washington
Institute for Prostate Cancer Research (IPCR)
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Patients in cohort 1 with a median daily hot flash score ≥ 6 after 12 weeks of therapy may cross-over to cohort 2.
Eligibility
Sex/Gender
MALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Must be willing to provide informed consent prior to any study specific procedures * Age ≥ 18 years * Documented histologically confirmed adenocarcinoma of the prostate * Patients must have evidence of newly diagnosed or relapsed metastatic hormone sensitive prostate cancer on CT, positron emission tomography (PET), MRI or bone scan * No prior chemotherapy for the treatment of hormone sensitive prostate cancer * No prior therapy with an LHRH analogue or next-generation androgen receptor-signaling inhibitor (e.g. abiraterone, enzalutamide, etc.). Participants may have initiated on a first-generation androgen receptor (AR) antagonist (e.g. bicalutamide) prior to enrollment * Hemoglobin ≥ 9 g/dL with no blood transfusion in the past 28 days (measured within 30 days prior to administration of study treatment) * Platelet count ≥ 100 x 10\^9/L (measured within 30 days prior to administration of study treatment) * Absolute neutrophil count (ANC) ≥ 1.5 x 10\^9/L (measured within 30 days prior to administration of study treatment) * Aspartate aminotransferase (AST) or serum glutamic oxaloacetic transaminase (SGOT)/alanine aminotransferase (ALT) or serum glutamic pyruvate transaminase (SGPT) ≤ 2.5 x institutional upper limit of normal (measured within 30 days prior to administration of study treatment) * Patient must have creatinine clearance estimated using the Cockcroft-Gault equation (measured within 30 days prior to administration of study treatment) * Total bilirubin ≤ 1.5 x institutional upper limit of normal (ULN) with exception for Gilbert's syndrome (measured within 30 days prior to administration of study treatment) * Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2 * Patients must have a life expectancy ≥ 16 weeks * Patients must be willing and able to comply with protocol for the duration of the study including undergoing treatment and scheduled visits and examinations * At least one lesion (measurable and/or non-measurable) that can be accurately assessed at baseline by CT, MRI and/or bone scan and is suitable for repeated assessment. Subjects without bone metastases must have measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) version (v) 1.1 * Male patients and their partners, who are sexually active and of childbearing potential, must agree to the use of two highly effective forms of contraception in combination, throughout the period of taking study treatment and for 6 months after last dose of study drug(s) to prevent pregnancy in a partner
Exclusion criteria
* Involvement in the planning and/or conduct of the study * Other malignancy unless curatively treated with no evidence of disease for ≥ 2 years. Exceptions include adequately treated non-melanoma skin cancer or non-muscle invasive bladder cancer * Patients with symptomatic uncontrolled brain metastases. A scan to confirm the absence of brain metastases is not required. Patient with spinal cord compression unless considered to have received definitive therapy for this and evidence of clinically stable disease for 28 days * Patients considered inappropriate to receive docetaxel chemotherapy by their treating provider * Use of corticosteroids at a dose equivalent to \> 10 mg of prednisone daily * Planning to receive concurrent treatment with another systemic cancer therapy, aside from an LHRH analogue * Major surgery within 2 weeks of starting study treatment and patients must have recovered from any effects of any major surgery * Patients considered a poor medical risk due to a serious, uncontrolled medical disorder, non-malignant systemic disease or active, uncontrolled infection. Examples include, but are not limited to, uncontrolled ventricular arrhythmia, uncontrolled major seizure disorder, uncontrolled hypertension (blood pressure \[BP\] ≥ 165/100), unstable spinal cord compression, superior vena cava syndrome or extensive interstitial lung disease * Patients with a known hypersensitivity to transdermal estradiol, LHRH analogue, ARSIs or any of the excipients of these products * Patients with known active hepatitis (i.e., hepatitis B or C) due to risk of transmitting the infection through body or other body fluids * Evidence of serious and/or unstable pre-existing medical, psychiatric or other condition (including laboratory abnormalities) that could interfere with patient safety or provision of informed consent to participate in this study * Any psychological, familial, sociological or geographical condition that could potentially interfere with compliance with the study protocol and follow-up schedule * Evidence of a pre-existing condition that, in the opinion of the investigator, would put the patient at risk from estradiol therapy. * Some examples include: history of blood clotting disorder, migraines with aura or other focal neurological symptom, angina (New York Heart Association grade III or higher) * Prior history of deep venous thrombosis or pulmonary embolism within 5 years prior to enrollment in the study and not currently on systemic anticoagulation * Excluded due to risk of venous thromboembolism from hormone supplementation * Patients with New York Heart Association (NYHA) class III or IV heart failure or history of a prior myocardial infarction (MI) or cerebrovascular accident (stroke or transient ischemic attack) within 5 years of enrollment to the study * Excluded due to increased risk of cardiovascular events with estradiol supplementation
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in median daily hot flash score | From baseline to a minimum of 12 weeks combination therapy | As measured by Mayo Clinic Hot Flash Daily score. Will calculate the difference between the first hot flash score after 12 weeks and the baseline hot flash score for each patient, and then use difference-in-difference analysis to compare the mean changes between cohorts 1 and 2 using a two-sample t-test. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in quality of life (QOL) domains | From baseline to end of study visit, up to 2 years | Assessed via patient-reported outcome measure questionnaires. Average change in QOL scores (total and for each domain) for each questionnaire will be calculated at each timepoint. A paired t-test will be used to assess for statistically significant changes in QOL from baseline to subsequent timepoints and linear mixed effects models will be used to evaluate trends over all timepoints. |
| Bone mineral density | From baseline to end of study visit, up to 2 years | Assessed from change in T-score (or Z-score) via dual energy x-ray absorptiometry. |
| Changes in metabolic parameters: Mean change in hemoglobin A1c | From baseline to end of study visit, up to 2 years | Assessed via results of hemoglobin A1c. |
| Changes in metabolic parameters: Mean change in lipid panel values | From baseline to end of study visit, up to 2 years | Assessed via results of lipid panel \[total cholesterol, low-density lipoprotein (LDL), high-density lipoprotein (HDL), and triglycerides\]. |
| Changes in sleep patterns and sleep quality | From cycle 1 to end of study visit, up to 2 years | Assessed via results of sleep questionnaire in combination with results of wearable sleep device to measure total sleep time, sleep onset latency and sleep efficiency. |
| Incidence of adverse events | Up to 2 years | Assessed according to Common Terminology Criteria for Adverse Events version 5.0. |
| Time to radiographic progression | From randomization to radiographic progression, up to 2 years | Assessed per Response Evaluation Criteria in Solid Tumors version 1.1 (soft tissue metastases) and Prostate Cancer Working Group 3 criteria (bone metastases). |
| Time to prostate specific antigen (PSA) progression | From randomization to PSA progression, up to 2 years | Based on Prostate Cancer Working Group 3 criteria. |
| Changes in immune cell composition | Up to 2 years | Change in neutrophil to lymphocyte ratio. |
Countries
United States
Contacts
CONTACTMichael Schweizer, MD
PRINCIPAL_INVESTIGATORMichael Schweizer, MD
Fred Hutch/University of Washington Cancer Consortium
Outcome results
None listed