Prostate CancerPhase 2NCT01620593
Castration Compared to Castration Plus Metformin as First Line Treatment for Patients With Advanced Prostate Cancer
A Phase 2 study testing Metformin in people with Prostate Cancer, run by The University of Texas Health Science Center at San Antonio at 1 site in United States.
Trial summary
Prostate cancer is the most common non-cutaneous cancer in men. Patients with recurrent or metastatic prostate cancer are treated with androgen-deprivation therapy, often termed castration therapy. 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?
- Metformin
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 41 participants
- Where
- 1 siteUnited States
- Study dates
- Apr 2011to Sep 2016
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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
- (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).
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- 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.
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country.
United States1 site
Cancer Therapy and Research Center University of Texas Health Science Center San Antonio
San Antonio, Texas, 78229
About this study
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.
Prostate cancer is the most common non-cutaneous cancer in men. Patients with recurrent or metastatic prostate cancer are treated with androgen-deprivation therapy, often termed castration therapy. While the short and medium term benefits of castration are clear in relation to therapeutic efficacy in patients with prostate cancer, it is now appreciated that the resulting hypogonadism associated with castration is responsible for adverse consequences or metabolic syndrome that include increase in body mass index (BMI) and fat mass, hyperinsulinemia and insulin resistance, hyperlipidemia, reduced lean body mass (LBM) and muscle strength, osteoporosis, sexual dysfunction, poor quality of life and higher cardiovascular mortality. Lower testosterone levels in men independently predict the development of metabolic syndrome. Low testosterone levels in men are associated with insulin resistance and diabetes. Metformin is commonly prescribed for the treatment of type II diabetes because it lowers both glucose and insulin levels. Studies show preliminary evidence that metformin might have both antineoplastic and chemopreventative activity. Castration therapy decreases insulin sensitivity, adversely alters lipid profiles and results in weight gain, and it may be associated with a greater incidence of diabetes and cardiovascular disease. Little is known about the optimal strategy to mitigate the adverse metabolic effects of castration in men with prostate cancer. The rationale for using metformin in castrated men with advanced prostate cancer stems from the observation that castration therapy is associated with the metabolic syndrome, hyperinsulinemia and insulin resistance. Furthermore, reports that hyperinsulinemia stimulates insulin receptor expression on prostate cancer leading to tumor growth and development of castrate resistant prostate cancer suggest metformin through its activation of the AMPK-LKBI pathway reduces liver gluconeogenesis secondarily decreasing insulin levels may circumvent tumor growth and resistance to castration therapy. More importantly, evidence that metformin inhibits the mTOR pathway implicates an added therapeutic benefit as an anti-cancer agent.
- Conditions
- Prostate Cancer
- Being tested
- Placebo, Metformin
- Keywords
- Prostate Cancer, Metformin, Castration therapy
- Medical subject headings
- Prostatic Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PlaceboDrug
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.
MetforminDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| Placebo | Placebo comparator | Metabolic consequences including development of hyperinsulinemia and insulin resistance using metformin compared to placebo in men on castration therapy. Receives: Drug: Placebo |
| Metformin | Active comparator | 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. Receives: Drug: Metformin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Metabolic Syndrome
Compare both cohorts of castrated men (metformin vs. placebo) with regard to metabolic consequences of castration therapy:change in weight.
Measured: Change from 0 weeks to 28 weeks
Metabolic Syndrome Waist Circumference
Compare both cohorts of castrated men (metformin vs. placebo) with regard to metabolic consequences of castration therapy:change in waist circumference.
Measured: Change from 12 to 28 weeks
Secondary outcomes (3)
PSA Response
Complete Response for PSA measure was defined as a PSA less than or equal to 4 ng/ml or undetectable value at 7 months.
Measured: 28 weeks
Treatment Failure
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.
Measured: 1 year
Number of Participants With Adverse Events
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
Measured: 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Jun 2012 (estimated)
- Study startApr 2011
- Primary completionJul 2016
- Study completionSep 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Prostate CancerStudies of the same condition, open and under way.
- More trials run by The University of Texas Health Science Center at San AntonioThe 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 41 participants (actual)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Devalingam Mahalingam, MD, PhD, Principal investigator, The University of Texas Health Science Center at San Antonio
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01620593
- Sponsor's protocol ID
- CTRC 10-21
- Other IDs
- HSC20110273H
- Status last verified
- Sep 2016
- First submitted
- 31 May 2012
- Last updated
- 23 May 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Roy S, Malone S, Grimes S, Morgan SC. Impact of Concomitant Medications on Biochemical Outcome in Localised Prostate Cancer Treated with Radiotherapy and Androgen Deprivation Therapy. Clin Oncol (R Coll Radiol). 2021 Mar;33(3):181-190. doi: 10.1016/j.clon.2020.09.005. Epub 2020 Sep 29.
PubMed 32994091
Study at a glance
From the registry record, last updated by the sponsor on 23 May 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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.
- ClinicalTrials.gov ID
- NCT01620593
- Acronym / sponsor ID
- CTRC 10-21
- Conditions
- Prostate Cancer
- Keywords
- Prostate Cancer, Metformin, Castration therapy
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 41 participants (actual)
- Lead sponsor
- The University of Texas Health Science Center at San AntonioUniversity, hospital or other
- Study start
- Apr 2011
- Primary completion
- Jul 2016 (actual)
- Study completion
- Sep 2016 (actual)
- First posted
- 15 Jun 2012 (estimated)
- Results
- Posted 22 May 2018
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Prostate cancer is the most common non-cutaneous cancer in men. Patients with recurrent or metastatic prostate cancer are treated with androgen-deprivation therapy, often termed castration therapy. While the short and medium term benefits of castration are clear in relation to therapeutic efficacy in patients with prostate cancer, it is now appreciated that the resulting hypogonadism associated with castration is responsible for adverse consequences or metabolic syndrome that include increase in body mass index (BMI) and fat mass, hyperinsulinemia and insulin resistance, hyperlipidemia, reduced lean body mass (LBM) and muscle strength, osteoporosis, sexual dysfunction, poor quality of life and higher cardiovascular mortality. Lower testosterone levels in men independently predict the development of metabolic syndrome. Low testosterone levels in men are associated with insulin resistance and diabetes. Metformin is commonly prescribed for the treatment of type II diabetes because it lowers both glucose and insulin levels. Studies show preliminary evidence that metformin might have both antineoplastic and chemopreventative activity. Castration therapy decreases insulin sensitivity, adversely alters lipid profiles and results in weight gain, and it may be associated with a greater incidence of diabetes and cardiovascular disease. Little is known about the optimal strategy to mitigate the adverse metabolic effects of castration in men with prostate cancer. The rationale for using metformin in castrated men with advanced prostate cancer stems from the observation that castration therapy is associated with the metabolic syndrome, hyperinsulinemia and insulin resistance. Furthermore, reports that hyperinsulinemia stimulates insulin receptor expression on prostate cancer leading to tumor growth and development of castrate resistant prostate cancer suggest metformin through its activation of the AMPK-LKBI pathway reduces liver gluconeogenesis secondarily decreasing insulin levels may circumvent tumor growth and resistance to castration therapy. More importantly, evidence that metformin inhibits the mTOR pathway implicates an added therapeutic benefit as an anti-cancer agent.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Placebo | Placebo comparator | Drug: PlaceboMetabolic consequences including development of hyperinsulinemia and insulin resistance using metformin compared to placebo in men on castration therapy. |
| Metformin | Active comparator | Drug: MetforminMetabolic 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- Male only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- (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
Key exclusion criteria (7 listed)
- 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.
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 |
|---|---|---|
| PlaceboAll 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. | Drug | Placebo |
| MetforminAll 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. | Drug | Metformin |
Primary outcome
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.
3 secondary outcomes
PSA Response
Time frame: 28 weeks
Treatment Failure
Time frame: 1 year
Number of Participants With Adverse Events
Time frame: 1 year
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 May 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 32994091Roy S, Malone S, Grimes S, Morgan SC. Impact of Concomitant Medications on Biochemical Outcome in Localised Prostate Cancer Treated with Radiotherapy and Androgen Deprivation Therapy. Clin Oncol (R Coll Radiol). 2021 Mar;33(3):181-190. doi: 10.1016/j.clon.2020.09.005. Epub 2020 Sep 29.
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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.
Devalingam Mahalingam, MD, PhD principal investigator
The University of Texas Health Science Center at San Antonio
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Metformin in people with Prostate Cancer, run by The University of Texas Health Science Center at San Antonio 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 9 inclusion and 7 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 23 May 2018. 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. Some participants in this study may receive a placebo. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 22 May 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Metabolic Syndrome (time frame: Change from 0 weeks to 28 weeks). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01620593, which also lists 1 linked publication.
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 23 May 2018; AzTrials last refreshed its copy on 6 Nov 2026.