Prostate CancerPhase 1NCT02339168
Enzalutamide and Metformin Hydrochloride in Treating Patients With Hormone-Resistant Prostate Cancer
A Phase 1 study testing Enzalutamide and Metformin Hydrochloride in people with Prostate Cancer, run by University of California, Davis at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older, men only
- Conditions the study is for
- Prostate Cancer
- What is being tested?
- Enzalutamide and Metformin Hydrochloride
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 25 participants
- Where
- 1 siteUnited States
- Study dates
- 22 Jun 2016to 24 Feb 2025
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- Men only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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
- Concurrent bisphosphonate or receptor activator of nuclear factor kappa-B (RANK)-ligand directed therapy for prevention of skeletal related events or treatment of osteoporosis is allowed
- Male patient and his female partner who is of childbearing potential must use 2 acceptable methods of birth control (one of which must include a condom as a barrier method of contraception) starting at screening and continuing throughout the study period and for 3 months after final study drug administration; two acceptable methods of birth control thus include the following: condom (barrier method of contraception) AND one of the following is required:
- Established use of oral, or injected or implanted hormonal method of contraception by the female partner
- Placement of an intrauterine device (IUD) or intrauterine system (IUS) by the female partner
- Additional barrier method: occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel film/cream/suppository by the female partner
- Tubal ligation in the female partner
- Vasectomy or other procedure resulting in infertility (e.g., bilateral orchiectomy), for more than 6 months
- Able to swallow the study drug and comply with study requirements
- Estimated life expectancy >= 6 months
- Ability to understand and the willingness to sign a written informed consent document
Who cannot join
- 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
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- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
University of California Davis Comprehensive Cancer Center
Sacramento, California, 95817
About this study
Official title: Enzalutamide and Metformin Combination Therapy to Overcome Autophagy Resistance in Castration Resistant Prostate Cancer
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.
Read the detailed description
PRIMARY OBJECTIVES:
- To determine the maximum tolerated dose (MTD) of enzalutamide when given in combination with metformin (metformin hydrochloride) to patients with castration resistant prostate cancer (CRPC), where fewer than 33% of patients experienced dose limiting toxicity (DLT) attributable to the study regimen and to recommend a phase II dose for the combination.
SECONDARY OBJECTIVES:
- To determine prostate-specific antigen (PSA) response in patients with CRPC with given enzalutamide in combination with metformin.
II. To determine PSA progression in patients with CRPC with given enzalutamide in combination with metformin.
III. To investigate the feasibility and safety of enzalutamide when given in combination with metformin hydrochloride to patients with CRPC.
IV. To obtain preliminary evidence of efficacy for this combination.
TERTIARY OBJECTIVES:
- To collect computed tomography (CT)-guided biopsies of metastatic soft tissue or bone tumor tissue for analysis of androgen receptor (AR) gene signature as an integrated biomarker (University of California San Francisco [UCSF] to conduct analysis).
II. To collect serum samples for the measurement of PSA levels and bone re-absorption markers.
OUTLINE: This is a dose-escalation study of metformin hydrochloride.
Patients receive enzalutamide orally (PO) once daily (QD) and metformin hydrochloride PO twice daily (BID). Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up at 4, 8, and 12 weeks.
- Conditions
- Prostate Cancer
- Being tested
- Enzalutamide, Metformin Hydrochloride
- Medical subject headings
- Prostatic Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
EnzalutamideDrug
Also called MDV3100, Xtandi
Given PO
Metformin HydrochlorideDrug
Also called Glucophage, Metformin HCl
Given PO
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Drug: Enzalutamide; Drug: Metformin Hydrochloride |
What is being measured
The primary outcome is the main question the study is designed to answer.
DLT graded accorded to the National Cancer institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0
Measured: 28 days
Secondary outcomes (6)
Incidence of adverse events graded according to NCI CTCAE version 4.0
The safety analysis population will consist of patients who received any amount of study drug. Clinical and laboratory adverse events will be summarized by coded term and severity. Laboratory values will be plotted over time.
Measured: 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
Confidence intervals for the PSA response rate will be calculated using the Clopper-Pearson method, and the PSA response rate will be tested against a null response rate of 50% using an exact binomial test.
Measured: 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
PSA progression by PCWG2 will be assessed and described.
Measured: Up to 12 weeks after last dose of study treatment
Radiographic disease progression, determined by Response Evaluation Criteria in Solid Tumors version 1.1
Measured: Up to 12 weeks after last dose of study treatment
Progression-free survival
Measured: 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
Time to treatment failure which includes discontinuing therapy because of disease progression, toxicity, or patient withdrawal
Measured: Up to 12 weeks after last dose of study treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Jan 2015 (estimated)
- Study start22 Jun 2016
- Primary completion15 Oct 2024
- Study completion24 Feb 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Prostate CancerStudies of the same condition, open and under way.
- More trials run by University of California, DavisThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 25 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of California, Davis
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI), Medivation, Inc., Astellas Pharma Inc
- Responsible party
- Sponsor
- Investigators
- Marc Dall'Era, MD, Principal investigator, University of California, Davis
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02339168
- Sponsor's protocol ID
- 680462
- Other IDs
- UCDCC#243, UCDCC#243, P30CA093373, NCI-2014-02668
- Status last verified
- Apr 2025
- First submitted
- 12 Jan 2015
- Last updated
- 1 May 2025
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 1 May 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Enzalutamide and Metformin Combination Therapy to Overcome Autophagy Resistance in Castration Resistant Prostate Cancer
- ClinicalTrials.gov ID
- NCT02339168
- Acronym / sponsor ID
- 680462
- Conditions
- Prostate Cancer
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 25 participants (actual)
- Lead sponsor
- University of California, DavisUniversity, hospital or other
- Collaborators
- National Cancer Institute (NCI), Medivation, Inc., Astellas Pharma Inc
- Study start
- 22 Jun 2016 (actual)
- Primary completion
- 15 Oct 2024 (actual)
- Study completion
- 24 Feb 2025 (actual)
- First posted
- 15 Jan 2015 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
PRIMARY OBJECTIVES:
- To determine the maximum tolerated dose (MTD) of enzalutamide when given in combination with metformin (metformin hydrochloride) to patients with castration resistant prostate cancer (CRPC), where fewer than 33% of patients experienced dose limiting toxicity (DLT) attributable to the study regimen and to recommend a phase II dose for the combination.
SECONDARY OBJECTIVES:
- To determine prostate-specific antigen (PSA) response in patients with CRPC with given enzalutamide in combination with metformin.
II. To determine PSA progression in patients with CRPC with given enzalutamide in combination with metformin.
III. To investigate the feasibility and safety of enzalutamide when given in combination with metformin hydrochloride to patients with CRPC.
IV. To obtain preliminary evidence of efficacy for this combination.
TERTIARY OBJECTIVES:
- To collect computed tomography (CT)-guided biopsies of metastatic soft tissue or bone tumor tissue for analysis of androgen receptor (AR) gene signature as an integrated biomarker (University of California San Francisco [UCSF] to conduct analysis).
II. To collect serum samples for the measurement of PSA levels and bone re-absorption markers.
OUTLINE: This is a dose-escalation study of metformin hydrochloride.
Patients receive enzalutamide orally (PO) once daily (QD) and metformin hydrochloride PO twice daily (BID). Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up at 4, 8, and 12 weeks.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| enzalutamide and metformin hydrochloride | Experimental | Drug: Enzalutamide, Drug: Metformin HydrochloridePatients receive enzalutamide PO QD and metformin hydrochloride PO BID. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. |
Who may qualify
- Ages
- 18 years and older
- Sex
- Male only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (25 listed)
- 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):
- 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
Key exclusion criteria (13 listed)
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| EnzalutamideAlso: MDV3100, XtandiGiven PO | Drug | enzalutamide and metformin hydrochloride |
| Metformin HydrochlorideAlso: Glucophage, Metformin HClGiven PO | Drug | enzalutamide and metformin hydrochloride |
Primary outcome
DLT graded accorded to the National Cancer institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0
Time frame: 28 days
6 secondary outcomes
Incidence of adverse events graded according to NCI CTCAE version 4.0
Time frame: 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
Time frame: 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
Time frame: Up to 12 weeks after last dose of study treatment
Radiographic disease progression, determined by Response Evaluation Criteria in Solid Tumors version 1.1
Time frame: Up to 12 weeks after last dose of study treatment
Progression-free survival
Time frame: 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
Time to treatment failure which includes discontinuing therapy because of disease progression, toxicity, or patient withdrawal
Time frame: Up to 12 weeks after last dose of study treatment
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 May 2025.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Marc Dall'Era, MD principal investigator
University of California, Davis
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Enzalutamide and Metformin Hydrochloride in people with Prostate Cancer, run by University of California, Davis at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 25 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 1 May 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
DLT graded accorded to the National Cancer institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 (time frame: 28 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 May 2025.