Estrogen to Improve Quality of Life for Men With Newly Diagnosed or Recurrent Metastatic Hormone Sensitive Prostate Cancer, EQUIP Trial

NCT07466498 | Not Yet Recruiting Phase 2 DMC FDA Drug

• 3 other identifiers: RG1126186NCI-2026-00800FHIRB0021151
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

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

Outcome Measures

Primary Outcomes (1)

• Change in median daily hot flash score

  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.

  From baseline to a minimum of 12 weeks combination therapy

Secondary Outcomes (9)

• Change in quality of life (QOL) domains

  From baseline to end of study visit, up to 2 years

• Bone mineral density

  From baseline to end of study visit, up to 2 years

• Changes in metabolic parameters: Mean change in hemoglobin A1c

  From baseline to end of study visit, up to 2 years

• Changes in metabolic parameters: Mean change in lipid panel values

  From baseline to end of study visit, up to 2 years

• Changes in sleep patterns and sleep quality

  From cycle 1 to end of study visit, up to 2 years

Study Arms (2)

Cohort 1 (LHRH agonist/antagonist and ARSI)

ACTIVE COMPARATOR

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.

Drug: Androgen Receptor Pathway Inhibitor; Procedure: Bone Scan; Procedure: Computed Tomography; Procedure: Dual X-ray Absorptiometry; Biological: Gonadotropin-releasing Hormone Analog; Procedure: Magnetic Resonance Imaging; Other: Survey Administration; Procedure: Biospecimen Collection

Cohort 2 (Estrogen and ARSI)

EXPERIMENTAL

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.

Drug: Androgen Receptor Pathway Inhibitor; Drug: Transdermal Estrogen; Procedure: Bone Scan; Procedure: Computed Tomography; Procedure: Dual X-ray Absorptiometry; Procedure: Magnetic Resonance Imaging; Other: Survey Administration; Procedure: Biospecimen Collection

Interventions

Androgen Receptor Pathway Inhibitor DRUG

Given per standard of care

Also known as: Androgen Receptor Signaling Inhibitor, AR Pathway Inhibitor, AR Signaling Inhibitor, AR Signaling Pathway Inhibitor, ARPI, ARSI

Cohort 1 (LHRH agonist/antagonist and ARSI); Cohort 2 (Estrogen and ARSI)

Transdermal Estrogen DRUG

Given via transdermal patch

Also known as: Divigel, Estrodiol Gel, EstroGel

Cohort 2 (Estrogen and ARSI)

Bone Scan PROCEDURE

Undergo bone scan

Also known as: Bone Scintigraphy

Cohort 1 (LHRH agonist/antagonist and ARSI); Cohort 2 (Estrogen and ARSI)

Computed Tomography PROCEDURE

Undergo CT scan

Also known as: CAT, CAT Scan, Computed Axial Tomography, Computerized Axial Tomography, Computerized axial tomography (procedure), Computerized Tomography, Computerized Tomography (CT) scan, CT, CT Scan, Diagnostic CAT Scan, Diagnostic CAT Scan Service Type, tomography

Cohort 1 (LHRH agonist/antagonist and ARSI); Cohort 2 (Estrogen and ARSI)

Dual X-ray Absorptiometry PROCEDURE

Undergo DEXA scan

Also known as: BMD scan, bone mineral density scan, DEXA, DEXA (Bone Density), DEXA Scan, dual energy x-ray absorptiometric scan, Dual Energy X-ray Absorptiometry, Dual X-Ray Absorptometry, DXA, DXA SCAN

Cohort 1 (LHRH agonist/antagonist and ARSI); Cohort 2 (Estrogen and ARSI)

Gonadotropin-releasing Hormone Analog BIOLOGICAL

Given per standard of care

Also known as: GnRH Agonist, GnRH Analog, Gonadotropin-Releasing Hormone Agonist, Gonadotropin-Releasing Hormone Analogue, LH-RH agonist, LH-RH Analogs, LHRH Agonist, luteinizing hormone-releasing hormone agonist, Luteinizing Hormone-Releasing Hormone Analog

Cohort 1 (LHRH agonist/antagonist and ARSI)

Magnetic Resonance Imaging PROCEDURE

Undergo MRI

Also known as: Magnetic Resonance, Magnetic Resonance Imaging (MRI), Magnetic resonance imaging (procedure), Magnetic Resonance Imaging Scan, Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance, MR, MR Imaging, MRI, MRI Scan, MRIs, NMR Imaging, NMRI, Nuclear Magnetic Resonance Imaging, sMRI, Structural MRI

Cohort 1 (LHRH agonist/antagonist and ARSI); Cohort 2 (Estrogen and ARSI)

Survey Administration OTHER

Ancillary studies

Cohort 1 (LHRH agonist/antagonist and ARSI); Cohort 2 (Estrogen and ARSI)

Biospecimen Collection PROCEDURE

Undergo blood sample collection

Also known as: Biological Sample Collection, Biospecimen Collected, Specimen Collection

Cohort 1 (LHRH agonist/antagonist and ARSI); Cohort 2 (Estrogen and ARSI)

Eligibility Criteria

• Age: 18 Years+
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Washington: lead
• Institute for Prostate Cancer Research (IPCR): collaborator

Study Sites (1)

Fred Hutch/University of Washington Cancer Consortium

Seattle, Washington, 98109, United States

Location

MeSH Terms

Conditions

Prostatic Neoplasms

Interventions

Estradiol; Absorptiometry, Photon; Bone Density; Gonadotropin-Releasing Hormone; Magnetic Resonance Spectroscopy; Specimen Handling

Condition Hierarchy (Ancestors)

Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Estrenes; Estranes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Estradiol Congeners; Gonadal Steroid Hormones; Gonadal Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Radiography; Diagnostic Imaging; Diagnostic Techniques and Procedures; Diagnosis; Densitometry; Photometry; Chemistry Techniques, Analytical; Investigative Techniques; Musculoskeletal Physiological Phenomena; Musculoskeletal and Neural Physiological Phenomena; Pituitary Hormone-Releasing Hormones; Hypothalamic Hormones; Peptide Hormones; Neuropeptides; Peptides; Amino Acids, Peptides, and Proteins; Oligopeptides; Nerve Tissue Proteins; Proteins; Spectrum Analysis; Clinical Laboratory Techniques

Study Officials

• Michael Schweizer, MD

  Fred Hutch/University of Washington Cancer Consortium

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Michael Schweizer, MD

CONTACT

206-606-6252; schweize@uw.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Patients in cohort 1 with a median daily hot flash score ≥ 6 after 12 weeks of therapy may cross-over to cohort 2.

Study Record Dates

• First Submitted: February 23, 2026
• First Posted: March 12, 2026
• Study Start (Estimated): August 1, 2026
• Primary Completion (Estimated): June 1, 2029
• Study Completion (Estimated): June 1, 2029
• Last Updated: March 12, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)