Castration Compared to Castration Plus Metformin as First Line Treatment for Patients With Advanced Prostate Cancer
![]() |
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. |
ClinicalTrials.gov Identifier: NCT01620593 |
Recruitment Status :
Completed
First Posted : June 15, 2012
Results First Posted : May 22, 2018
Last Update Posted : May 23, 2018
|
- Study Details
- Tabular View
- Study Results
- Disclaimer
- How to Read a Study Record
Condition or disease | Intervention/treatment | Phase |
---|---|---|
Prostate Cancer | Drug: Placebo Drug: Metformin | Phase 2 |
Study Type : | Interventional (Clinical Trial) |
Actual Enrollment : | 41 participants |
Allocation: | Randomized |
Intervention Model: | Parallel Assignment |
Masking: | Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor) |
Primary Purpose: | Treatment |
Official Title: | Phase II, Randomized, Placebo Controlled, Double Blind, Prospective Study of Castration Compared to Castration Plus Metformin as First Line Treatment for Patients With Advanced Prostate Cancer. |
Study Start Date : | April 2011 |
Actual Primary Completion Date : | July 2016 |
Actual Study Completion Date : | September 2016 |

Arm | Intervention/treatment |
---|---|
Placebo Comparator: Placebo
Metabolic consequences including development of hyperinsulinemia and insulin resistance using metformin compared to placebo in men on castration therapy.
|
Drug: Placebo
All eligible subjects will be randomized in a 1:l manner to receive a bottle containing sufficient 500mg tablets of placebo after castration, blinded to the patient and the study team. |
Active Comparator: Metformin
Metabolic consequences including development of hyperinsulinemia and insulin resistance using metformin compared to placebo in men on castration therapy. In the rare case where a patient may not tolerate 500 mg three times a day, he may remain on the study taking only 500 mg twice a day.
|
Drug: Metformin
All eligible subjects will be randomized in a 1:l manner to receive a bottle containing sufficient 500mg tablets of metformin after castration, blinded to the patient and the study team. |
- Metabolic Syndrome [ Time Frame: Change from 0 weeks to 28 weeks ]Compare both cohorts of castrated men (metformin vs. placebo) with regard to metabolic consequences of castration therapy:change in weight.
- Metabolic Syndrome Waist Circumference [ Time Frame: Change from 12 to 28 weeks ]Compare both cohorts of castrated men (metformin vs. placebo) with regard to metabolic consequences of castration therapy:change in waist circumference.
- PSA Response [ Time Frame: 28 weeks ]Complete Response for PSA measure was defined as a PSA less than or equal to 4 ng/ml or undetectable value at 7 months.
- Treatment Failure [ Time Frame: 1 year ]Progression time from randomization to the earliest disease progression defined as an increase of 20% or more as per RECIST criteria. Patients will not be removed from protocol treatment for PSA progression alone in the first 12 weeks on this study. Further rise in PSA even in the absence of deterioration of pre-existing lesions will constitute treatment failure. Adverse event leading to withdrawal related to metformin or placebo or castration treatment. Death from any cause. Patients unwillingness to continue. Patient's non-compliance with taking the study intervention - 50% or higher.
- Number of Participants With Adverse Events [ Time Frame: 1 year ]
The safety and tolerability of metformin with castration therapy as compared to castration therapy alone as measured by the number of subjects experiencing adverse events using CTCAE (common terminology criteria for adverse events) version 4 criteria. Grades are assigned to each adverse event where:
Grade 1 is mild symptoms Grade 2 is moderate symptoms Grade 3 is severe or medically significant but not immediately life-threatening symptoms Grade 4 is life-threatening consequences, where urgent intervention is indicated Grade 5 is death related to the adverse event

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
Sexes Eligible for Study: | Male |
Accepts Healthy Volunteers: | No |
Inclusion Criteria:
(Eligible subjects must meet one of the inclusion criteria 1-3 and all of items 4-6)
-
Men with metastatic prostate cancer that require castration therapy with either using an LHRH analogue or surgical castration are eligible. Complete androgen blockade using anti-androgen therapy prior to castration or up to 4 weeks following castration therapy is permitted to prevent disease flare. Thereafter anti-androgen therapy may continue or be discontinued based on treating physicians preference.
OR
-
Any men with prostate cancer who are candidates for castration therapy despite no evidence of definite metastatic disease including patient with biochemical failure or 'rising PSA' are also permitted to enter study provided castration therapy is planned for a minimum of a year. Patients with biochemical failure prior to enrolment should have also have already received appropriate salvage therapy. Men with prostate cancer who have already started castration therapy are also permitted to enter study provided castration therapy was initiated within one month of study entry.
OR
- Men with prostate cancer previously treated with castration therapy for management of localized prostate cancer in the adjuvant setting or in combination with radiation therapy are permitted to enter study provided they currently have known metastatic disease and have non-castrate testosterone levels (Testosterone > 50 ng/dL).
- An ECOG performance status of 0-2.
- Patients will need to have documentation of metastatic disease in bone and/or soft tissue, and a baseline PSA of ≥ 5 ng/ml. If patients have already had castration therapy, their baseline PSA value will be reflective of the value prior to castration. Patients with biochemical failures, with rising PSA (baseline PSA does not need to be ≥ 5 nglml to be eligible), without metastatic disease are also eligible if castration therapy is indicated for minimum of 7 months and for these patients any PSA value is permitted.
- Patients must have provided informed consent, be willing to have blood specimens taken, and exhibit no severe other medical or psychiatric problems.
Exclusion Criteria:
- Patients with severe medical or psychiatric diseases are INELIGIBLE. (Patients with stable chronic diseases such as high cholesterol or hypertension ARE eligible.) Examples of problems that would make patients INELIGIBLE include severe heart failure, or hypoxia due to severe lung disease.
- Patients with clinical or biochemical evidence of renal failure or liver failure are INELIGIBLE. Creatinine and bilirubin needs to be less than or equal to 1.3~up per limit of normal (ULN), and ASTIALT less than or equal to 2.5 x ULN unless liver metastasis is present then up to 5 X ULN permitted).
- Patients already receiving metformin or anti-diabetic medications are INELIGIBLE.
- If any patient develops symptomatic diabetes requiring drug therapy, he must receive such a therapy, which may include metformin. This must be documented, and the patient will not continue on the study.
- Patients with important infections requiring antibiotics are INELIGIBLE, but patients who acquire minor infections while on the study may remain on the study.
- Alcohol abuse problems make patients INELIGIBLE. Patients need to be consuming less than or equal to 14 units of alcohol weekly.
- Patients with history or evidence of lactic acidosis or metabolic acidosis will be excluded.

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01620593
United States, Texas | |
Cancer Therapy and Research Center University of Texas Health Science Center San Antonio | |
San Antonio, Texas, United States, 78229 |
Principal Investigator: | Devalingam Mahalingam, MD, PhD | University of Texas Health Science Center San Antonio |
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: | The University of Texas Health Science Center at San Antonio |
ClinicalTrials.gov Identifier: | NCT01620593 |
Other Study ID Numbers: |
CTRC 10-21 HSC20110273H ( Other Identifier: UTHSCSA IRB ) |
First Posted: | June 15, 2012 Key Record Dates |
Results First Posted: | May 22, 2018 |
Last Update Posted: | May 23, 2018 |
Last Verified: | September 2016 |
Prostate Cancer Metformin Castration therapy |
Prostatic Neoplasms Genital Neoplasms, Male Urogenital Neoplasms Neoplasms by Site Neoplasms |
Prostatic Diseases Metformin Hypoglycemic Agents Physiological Effects of Drugs |