Enzalutamide and Metformin Hydrochloride in Treating Patients With Hormone-Resistant Prostate Cancer
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|ClinicalTrials.gov Identifier: NCT02339168|
Recruitment Status : Active, not recruiting
First Posted : January 15, 2015
Last Update Posted : June 11, 2018
|Condition or disease||Intervention/treatment||Phase|
|Prostate Cancer||Drug: Enzalutamide Drug: Metformin Hydrochloride||Phase 1|
I. 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.
I. 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.
I. 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 Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||24 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Enzalutamide and Metformin Combination Therapy to Overcome Autophagy Resistance in Castration Resistant Prostate Cancer|
|Study Start Date :||June 2016|
|Estimated Primary Completion Date :||December 2018|
|Estimated Study Completion Date :||December 2019|
Experimental: enzalutamide and metformin hydrochloride
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: Metformin Hydrochloride
- DLT graded accorded to the National Cancer institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 [ Time Frame: 28 days ]
- Incidence of adverse events graded according to NCI CTCAE version 4.0 [ Time Frame: Up to 12 weeks after last dose of study treatment ]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.
- 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 ]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.
- 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 ]PSA progression by PCWG2 will be assessed and described.
- 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 ]
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02339168
|United States, California|
|University of California Davis Comprehensive Cancer Center|
|Sacramento, California, United States, 95817|
|Principal Investigator:||Christopher Evans||University of California, Davis|