Prostate CancerPhase 2LIGANDNCT02497638
LIpitor and biGuanide to Androgen Delay Trial
A Phase 2 study testing Metformin and Atorvastatin in people with Prostate Cancer, run by University Health Network, Toronto at 1 site in Canada.
Trial summary
This study is a randomized trial examining the administration of a combination of biguanide metformin and atorvastatin ("Lipitor") to men who are experiencing rising prostate-specific antigen (PSA) levels, despite having undergone radical therapy (surgery and/or radiation). Read more about this study
- Who is it for?
- Ages 18 to 80 years, men only
- Conditions the study is for
- Prostate Cancer
- What is being tested?
- Metformin and Atorvastatin
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 0 participants
- Where
- 1 siteCanada
- Study dates
- Dec 2021to Dec 2022
- Phase
- Phase 2
- 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 to 80 years
- Men only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Willing and able to provide informed consent
- Histologically confirmed adenocarcinoma of the prostate
- History of radical therapy (i.e., radical prostatectomy, radiotherapy, brachytherapy or prostatectomy with salvage radiotherapy)
- Serum testosterone levels 8.0 nmol/L (230 ng/dL) or greater
- Not currently undergoing treatment for hyperlipidemia or diabetes mellitus
- LDL-cholesterol levels 5 mmol/L or lower
- HgA1c 6.5% or lower
- PSA levels between 2 and 5 ng/mL
Who cannot join
- Subjects that have been treated for prostate cancer with any of the following:
- Cytotoxic chemotherapy; ii. Hormonal therapy within past 3 years; iii. Oral glucocorticoids; iv. Gonadotropin-releasing hormone (GnRH) analogues (e.g., leuprolide, goserelin, degarelix)
- Past treatment with the 5-α reductase inhibitors finasteride and dutasteride within past 5 years
- Past treatment with drugs with antiandrogenic properties (e.g., flutamide, bicalutamide, ketoconazole, progestational agents) within 6 months prior to screening
- Use of metformin or statins within past 2 years
- Planned or concurrent use of metformin, sulfonylureas, thiazolidinediones or insulin for any reason
Show all 11Show fewer
- Known hypersensitivity or intolerance to metformin or atorvastatin
- Any clinically significant laboratory abnormalities (e.g., severe renal or hepatic impairment) which in the judgment of the investigator would affect the patient's health or the outcome of the trial
- Any condition associated with increased risk of metformin-associated lactic acidosis (e.g., congestive heart failure defined as New York Heart Association (NYHA) class III or IV, history of any type of acidosis, habitual intake of 4 or more alcoholic beverages per day)
- Abnormal liver function test
- Abnormal organ and marrow function
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Randomized, Double Blind, Trial of Metformin and Atorvastatin in Delaying Androgen Deprivation Therapy Among Men With Rising PSA Following Radical Prostatectomy or Radiotherapy: The LIGAND (LIpitor and biGuanide to Androgen Delay) Trial
This study is a randomized trial examining the administration of a combination of biguanide metformin and atorvastatin ("Lipitor") to men who are experiencing rising prostate-specific antigen (PSA) levels, despite having undergone radical therapy (surgery and/or radiation).
- Conditions
- Prostate Cancer
- Being tested
- Metformin, Atorvastatin, Placebo (corresponding to metformin), Placebo (corresponding to atorvastatin)
- Keywords
- metformin, atorvastatin, prostate-specific antigen, biochemical recurrence
- Medical subject headings
- Prostatic Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MetforminDrug
Also called biguanide
One month run-in of 850 mg metformin once daily, followed by 850 mg twice daily of metformin until progression.
AtorvastatinDrug
Also called lipitor
Atorvastatin 20 mg once daily until progression.
Placebo (corresponding to metformin)Drug
One month of one placebo tablet (corresponding to metformin) once daily, followed by one placebo tablet twice daily until progression.
Placebo (corresponding to atorvastatin)Drug
One placebo tablet (corresponding to atorvastatin) once daily until progression.
| Study group | Role | What they receive |
|---|---|---|
| Metformin and Atorvastatin | Experimental | Atorvastatin 20 mg once daily until progression with one month run-in of 850 mg metformin once daily, followed by 850 mg twice daily of metformin until progression. Receives: Drug: Metformin; Drug: Atorvastatin |
| Placebo | Placebo comparator | One placebo tablet (corresponding to atorvastatin) once daily until progression, with one month of one placebo tablet (corresponding to metformin) once daily, followed by one placebo tablet twice daily until progression. Receives: Drug: Placebo (corresponding to metformin); Drug: Placebo (corresponding to atorvastatin) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Time to disease progression (defined as PSA rise to 10 ng/mL or greater, development of clinically overt metastases) or patient/physician desire for androgen deprivation therapy.
Measured: From date of randomization until the date of progression or patient/physician desire for androgen deprivation therapy, whichever comes first, assessed up to 36 months.
Secondary outcomes (10)
Time to androgen deprivation therapy
Measured: From date of randomization until the date of progression or patient/physician desire for androgen deprivation therapy, whichever comes first, assessed up to 36 months.
Time to PSA progression
Measured: From date of randomization until the date of progression or patient/physician desire for androgen deprivation therapy, whichever comes first, assessed up to 36 months.
Time to disease progression
Measured: From date of randomization until the date of progression or patient/physician desire for androgen deprivation therapy, whichever comes first, assessed up to 36 months.
Body mass index
Relationship between body mass index and response to anti-metabolic and anti-cholesterol therapy
Measured: From date of randomization until the date of progression or patient/physician desire for androgen deprivation therapy, whichever comes first, assessed up to 36 months.
Circulating glycated hemoglobin levels
Relationship between circulating glycated hemoglobin levels and response to anti-metabolic and anti-cholesterol therapy
Measured: From date of randomization until the date of progression or patient/physician desire for androgen deprivation therapy, whichever comes first, assessed up to 36 months.
C-peptide levels
Relationship between C-peptide levels and response to anti-metabolic and anti-cholesterol therapy
Measured: From date of randomization until the date of progression or patient/physician desire for androgen deprivation therapy, whichever comes first, assessed up to 36 months.
Adipokine levels
Relationship between adipokine levels and response to anti-metabolic and anti-cholesterol therapy
Measured: From date of randomization until the date of progression or patient/physician desire for androgen deprivation therapy, whichever comes first, assessed up to 36 months.
LDL/HDL cholesterol levels
Relationship between LDL/HDL cholesterol levels and response to anti-metabolic and anti-cholesterol therapy
Measured: From date of randomization until the date of progression or patient/physician desire for androgen deprivation therapy, whichever comes first, assessed up to 36 months.
Triglyceride levels
Relationship between triglyceride levels and response to anti-metabolic and anti-cholesterol therapy
Measured: From date of randomization until the date of progression or patient/physician desire for androgen deprivation therapy, whichever comes first, assessed up to 36 months.
Incidence of adverse events during administration of metformin and atorvastatin to men with prostate cancer.
Assessment of incidence of adverse events from the administration of metformin and atorvastatin to men with prostate cancer.
Measured: From date of randomization until the date of progression or patient/physician desire for androgen deprivation therapy, whichever comes first, assessed up to 36 months.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Jul 2015 (estimated)
- Study startDec 2021 (estimated)
- Primary completionDec 2021 (estimated)
- Study completionDec 2022 (estimated)
Why it stopped: Drug intervention no longer relevant for the proposed population
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 Health Network, TorontoThe 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
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- University Health Network, Toronto
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Robert Hamilton, MD, MPH, FRCSC, Principal investigator, University Health Network, TorontoNeil Fleshner, MD, MPH, FRCSC, Principal investigator, University Health Network, Toronto
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02497638
- Sponsor's protocol ID
- 15-053
- Acronym
- LIGAND
- Status last verified
- Apr 2021
- First submitted
- 19 Jun 2015
- Last updated
- 19 Apr 2021
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 19 Apr 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized, Double Blind, Trial of Metformin and Atorvastatin in Delaying Androgen Deprivation Therapy Among Men With Rising PSA Following Radical Prostatectomy or Radiotherapy: The LIGAND (LIpitor and biGuanide to Androgen Delay) Trial
- ClinicalTrials.gov ID
- NCT02497638
- Acronym / sponsor ID
- LIGAND / 15-053
- Conditions
- Prostate Cancer
- Keywords
- metformin, atorvastatin, prostate-specific antigen, biochemical recurrence
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Drug intervention no longer relevant for the proposed population
- Enrolment
- 0 participants (actual)
- Lead sponsor
- University Health Network, TorontoUniversity, hospital or other
- Study start
- Dec 2021 (estimated)
- Primary completion
- Dec 2021 (estimated)
- Study completion
- Dec 2022 (estimated)
- First posted
- 14 Jul 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 study is a randomized trial examining the administration of a combination of biguanide metformin and atorvastatin ("Lipitor") to men who are experiencing rising prostate-specific antigen (PSA) levels, despite having undergone radical therapy (surgery and/or radiation).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Metformin and Atorvastatin | Experimental | Drug: Metformin, Drug: AtorvastatinAtorvastatin 20 mg once daily until progression with one month run-in of 850 mg metformin once daily, followed by 850 mg twice daily of metformin until progression. |
| Placebo | Placebo comparator | Drug: Placebo (corresponding to metformin), Drug: Placebo (corresponding to atorvastatin)One placebo tablet (corresponding to atorvastatin) once daily until progression, with one month of one placebo tablet (corresponding to metformin) once daily, followed by one placebo tablet twice daily until progression. |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- Male only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Willing and able to provide informed consent
- Histologically confirmed adenocarcinoma of the prostate
- History of radical therapy (i.e., radical prostatectomy, radiotherapy, brachytherapy or prostatectomy with salvage radiotherapy)
- Serum testosterone levels 8.0 nmol/L (230 ng/dL) or greater
- Not currently undergoing treatment for hyperlipidemia or diabetes mellitus
Key exclusion criteria (11 listed)
- Subjects that have been treated for prostate cancer with any of the following:
- Past treatment with the 5-α reductase inhibitors finasteride and dutasteride within past 5 years
- Past treatment with drugs with antiandrogenic properties (e.g., flutamide, bicalutamide, ketoconazole, progestational agents) within 6 months prior to screening
- Use of metformin or statins within past 2 years
- Planned or concurrent use of metformin, sulfonylureas, thiazolidinediones or insulin for any reason
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 |
|---|---|---|
| MetforminAlso: biguanideOne month run-in of 850 mg metformin once daily, followed by 850 mg twice daily of metformin until progression. | Drug | Metformin and Atorvastatin |
| AtorvastatinAlso: lipitorAtorvastatin 20 mg once daily until progression. | Drug | Metformin and Atorvastatin |
| Placebo (corresponding to metformin)One month of one placebo tablet (corresponding to metformin) once daily, followed by one placebo tablet twice daily until progression. | Drug | Placebo |
| Placebo (corresponding to atorvastatin)One placebo tablet (corresponding to atorvastatin) once daily until progression. | Drug | Placebo |
Primary outcome
Time to disease progression (defined as PSA rise to 10 ng/mL or greater, development of clinically overt metastases) or patient/physician desire for androgen deprivation therapy.
Time frame: From date of randomization until the date of progression or patient/physician desire for androgen deprivation therapy, whichever comes first, assessed up to 36 months.
10 secondary outcomes
Time to androgen deprivation therapy
Time frame: From date of randomization until the date of progression or patient/physician desire for androgen deprivation therapy, whichever comes first, assessed up to 36 months.
Time to PSA progression
Time frame: From date of randomization until the date of progression or patient/physician desire for androgen deprivation therapy, whichever comes first, assessed up to 36 months.
Time to disease progression
Time frame: From date of randomization until the date of progression or patient/physician desire for androgen deprivation therapy, whichever comes first, assessed up to 36 months.
Body mass index
Time frame: From date of randomization until the date of progression or patient/physician desire for androgen deprivation therapy, whichever comes first, assessed up to 36 months.
Circulating glycated hemoglobin levels
Time frame: From date of randomization until the date of progression or patient/physician desire for androgen deprivation therapy, whichever comes first, assessed up to 36 months.
C-peptide levels
Time frame: From date of randomization until the date of progression or patient/physician desire for androgen deprivation therapy, whichever comes first, assessed up to 36 months.
Adipokine levels
Time frame: From date of randomization until the date of progression or patient/physician desire for androgen deprivation therapy, whichever comes first, assessed up to 36 months.
LDL/HDL cholesterol levels
Time frame: From date of randomization until the date of progression or patient/physician desire for androgen deprivation therapy, whichever comes first, assessed up to 36 months.
Triglyceride levels
Time frame: From date of randomization until the date of progression or patient/physician desire for androgen deprivation therapy, whichever comes first, assessed up to 36 months.
Incidence of adverse events during administration of metformin and atorvastatin to men with prostate cancer.
Time frame: From date of randomization until the date of progression or patient/physician desire for androgen deprivation therapy, whichever comes first, assessed up to 36 months.
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Apr 2021.
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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.
Robert Hamilton, MD, MPH, FRCSC principal investigator
University Health Network, Toronto
Neil Fleshner, MD, MPH, FRCSC principal investigator
University Health Network, Toronto
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 and Atorvastatin in people with Prostate Cancer, run by University Health Network, Toronto at 1 site in Canada.
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 8 inclusion and 11 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: withdrawn, as of the sponsor's last update on 19 Apr 2021. 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 Canada. 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?
The study was withdrawn before enrolling participants, so there are no results.
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?
Time to disease progression (defined as PSA rise to 10 ng/mL or greater, development of clinically overt metastases) or patient/physician desire for androgen deprivation therapy. (time frame: From date of randomization until the date of progression or patient/physician desire for androgen deprivation therapy, whichever comes first, assessed up to 36 months.). 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 19 Apr 2021.