Enzalutamide and Metformin Hydrochloride in Treating Patients With Hormone-Resistant Prostate Cancer

NCT02339168 | Completed Phase 1 DMC

• 4 other identifiers: 680462UCDCC#243P30CA093373NCI-2014-02668
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 1

Brief Summary

This phase I trial studies the side effects and best dose of metformin hydrochloride when given together with enzalutamide in treating patients with prostate cancer that has not responded to previous treatment with hormones. Hormone therapy using enzalutamide may fight prostate cancer by lowering the amount of androgens the body makes and blocking the use of androgens by the tumor cells. Metformin hydrochloride, used for diabetes, may also help kill tumor cells. Giving enzalutamide together with metformin hydrochloride may kill more tumor cells.

Conditions

Prostate Cancer

Outcome Measures

Primary Outcomes (1)

• DLT graded accorded to the National Cancer institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0

  28 days

Secondary Outcomes (6)

• Incidence of adverse events graded according to NCI CTCAE version 4.0

  Up to 12 weeks after last dose of study treatment

• PSA response rate as determined by percent of patients achieving >= 50% PSA decline following initiation of treatment

  Up to 12 weeks after last dose of study treatment

• PSA progression by Prostate Cancer Working Group (PCWG) 2, defined as the date that a 25% or greater increase and an absolute increase of 2 ng/mL or more from the nadir is documented, which is confirmed by a second value obtained 3 or more weeks later

  Up to 12 weeks after last dose of study treatment

• Radiographic disease progression, determined by Response Evaluation Criteria in Solid Tumors version 1.1

  Up to 12 weeks after last dose of study treatment

• Progression-free survival

  Time from study entry to disease progression in PSA, bone or soft-tissue, symptoms, or death, assessed up to 12 weeks after last dose of study treatment

Study Arms (1)

enzalutamide and metformin hydrochloride

EXPERIMENTAL

Patients receive enzalutamide PO QD and metformin hydrochloride PO BID. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Drug: Enzalutamide; Drug: Metformin Hydrochloride

Interventions

Enzalutamide DRUG

Given PO

Also known as: MDV3100, Xtandi

enzalutamide and metformin hydrochloride

Metformin Hydrochloride DRUG

Given PO

Also known as: Glucophage, Metformin HCl

enzalutamide and metformin hydrochloride

Eligibility Criteria

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

You may qualify if:

• Patients must have histologically or cytologically confirmed prostate cancer with a Gleason score available or interpretable; patients must have prostate cancer deemed to be castration-resistant by one or more of the following criteria (despite androgen deprivation and anti-androgen withdrawal when applicable):
• Progression of unidimensionally measurable disease assessed within 28 days prior to initial administration of drug
• Progression of evaluable but not measurable disease assessed within 28 days prior to initial administration of drug for PSA evaluation and within 42 days for imaging studies (e.g, bone scans)
• NOTE: rising PSA, defined as at least two consecutive rises in PSA to be documented over a reference value (measure 1); the first rising PSA (measure 2) should be taken at least 7 days after the reference value; a third confirmatory PSA measure (2nd beyond the reference level) should be greater than the second measure, and it must be obtained at least 7 days after the 2nd measure; if this is not the case, a fourth PSA is required to be taken and be greater than the second measure; measurable disease is not required
• Patients who have measurable disease must have had X-rays, scans or physical examinations used for tumor measurement completed within 28 days prior to initial administration of drug
• Patients must have non-measurable disease (such as nuclear medicine bone scans) and non-target lesions (such as PSA level) assessed within 28 days prior to initial administration of drug
• Soft tissue disease that has been radiated within the two months prior to registration is not assessable as measurable disease; soft tissue disease that has been radiated two or more months prior to registration is assessable as measurable disease provided that the lesion has progressed following radiation; patients must have at least one measurable lesion outside the previously irradiated region in order to be considered to have measurable disease
• Patients must have been surgically or medically castrated; if the method of castration was luteinizing hormone-releasing hormone (LHRH) agonists (leuprolide or goserelin), then the patient must be willing to continue the use of LHRH agonists; serum testosterone must be at castrate levels (\< 50 ng/dL) at least 14 days prior to registration
• If the patient has been treated with non-steroidal anti-androgens (flutamide, bicalutamide or nilutamide) or other hormonal treatment (such as ketoconazole), these agents must have been stopped at least 28 days prior to enrollment for flutamide or ketoconazole, and at least 42 days prior to enrollment for bicalutamide or nilutamide; and the patients must have demonstrated progression of disease since the agents were suspended
• Eastern Cooperative Oncology Group (ECOG) performance status 0-2
• Absolute neutrophil count \>= 1,500/mcL
• Platelets \>= 100,000/mcL
• Total bilirubin within normal institutional limits
• Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase \[SGOT\])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) =\< 2.5 x institutional upper limit of normal
• Creatinine within normal institutional limits OR creatinine clearance \>= 60 mL/min/1.73 m\^2 for patients with creatinine levels above institutional normal

You may not qualify if:

• Patients who have had radiotherapy within 2 weeks prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier
• Patients with prior history of seizure, underlying brain injury with loss of consciousness, transient ischemic attack within the past 12 months, cerebral vascular accident, brain arteriovenous malformation or the use of concomitant medications that may lower the seizure threshold or other conditions predisposing to seizure
• Patients who are receiving any other investigational agents
• Patients who are currently taking metformin; prior metformin use is allowed if last dose was 3 months previous to this trial
• Patients with diabetes on a different agent or patients with rheumatoid arthritis taking hydroxychloroquine (Plaquenil)
• Greater than 2 prior therapies in metastatic CRPC (including single-agent docetaxel, abiraterone); abiraterone can only be taken pre-chemotherapy
• Prior cabazitaxel or radium 233 for prostate cancer
• Patients with known brain metastases should be excluded from this clinical trial
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to enzalutamide or metformin
• Participation in a previous clinical trial of enzalutamide or an investigational agent that inhibits the androgen receptor (ARN-509) or androgen synthesis
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
• Patients on antipsychotic medication
• Human immunodeficiency virus (HIV)-positive patients on combination antiretroviral therapy are ineligible

Sponsors & Collaborators

• University of California, Davis: lead
• National Cancer Institute (NCI): collaborator
• Medivation, Inc.: collaborator
• Astellas Pharma Inc: collaborator

Study Sites (1)

University of California Davis Comprehensive Cancer Center

Sacramento, California, 95817, United States

Location

MeSH Terms

Conditions

Prostatic Neoplasms

Interventions

enzalutamide; Metformin

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)

Biguanides; Guanidines; Amidines; Organic Chemicals

Study Officials

• Marc Dall'Era, MD

  University of California, Davis

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 12, 2015
• First Posted: January 15, 2015
• Study Start: June 22, 2016
• Primary Completion: October 15, 2024
• Study Completion: February 24, 2025
• Last Updated: May 1, 2025

Record last verified: 2025-04

Locations

US (1)