Recruiting
Phase 2

Estrogen & Androgen Inhibitor

Sponsor:

Fred Hutchinson Cancer Center

Code:

NCT07466498

Conditions

Castration-Sensitive Prostate Adenocarcinoma

Metastatic Castration-Sensitive Prostate Adenocarcinoma

Stage IVB Prostate Cancer AJCC v8

Eligibility Criteria

Sex: Male

Age: 18+

Healthy Volunteers: Not accepted

Interventions

Androgen Receptor Pathway Inhibitor

Transdermal Estrogen

Bone Scan

Computed Tomography

Dual X-ray Absorptiometry

Study Details

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.

Conditions

Castration-Sensitive Prostate Adenocarcinoma

Metastatic Castration-Sensitive Prostate Adenocarcinoma

Stage IVB Prostate Cancer AJCC v8

Study ID

NCT07466498

Start date

Nov 1, 2026

Status verified date

Mar, 2026

Completion date

Jun 1, 2029

Anticipated

Primary completion date

Jun 1, 2029

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: Male

Age: 18+

Healthy Volunteers: Not accepted

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

Study Design

Enrollment

60 participants

Anticipated

Allocation

Randomized

Intervention Model

Parallel Assignment

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

active comparator: Cohort 1 (LHRH agonist/antagonist and ARSI)

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 CT scan or MRI, bone scan, DEXA scan and blood sample collection throughout the study.

experimental: Cohort 2 (Estrogen and ARSI)

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.

Interventions

Androgen Receptor Pathway Inhibitor

Given per standard of care

Transdermal Estrogen

Given via transdermal patch

Bone Scan

Undergo bone scan

Computed Tomography

Undergo CT scan

Dual X-ray Absorptiometry

Undergo DEXA scan

Gonadotropin-releasing Hormone Analog

Given per standard of care

Magnetic Resonance Imaging

Undergo MRI

Survey Administration

Ancillary studies

Biospecimen Collection

Undergo blood sample collection

Primary outcome measure

  • Change in median daily hot flash score [ Time Frame: From baseline to a minimum of 12 weeks combination therapy ]

Central Contacts and Locations

Central contacts

Michael Schweizer, MD

206-606-6252schweize@uw.edu

Locations

Fred Hutch/University of Washington Cancer Consortium

Recruiting

Seattle, Washington, United States, 98109

Contacts

Michael Schweizer, MD

206-606-6252schweize@uw.edu

Principal Investigator:

Michael Schweizer, MD

More Information

Sponsor

Fred Hutchinson Cancer Center

Last update posted

Oct 16, 2026

Last verified

Mar, 2026

Trial information was received from ClinicalTrials.gov and was last updated on 2026-10-17. This information was provided to ClinicalTrials.gov by Fred Hutchinson Cancer Center on 2026-10-16. Recruitment status is synced daily from ClinicalTrials.gov and may not reflect the sponsor's current status. Confirm during your call.