Recurrent Prostate CarcinomaPhase 2PRIMANCT02420652
Metformin Hydrochloride and Aspirin in Treating Patients With Hormone-Dependent Prostate Cancer That Has Progressed After Surgery or Radiation Therapy
A Phase 2 study testing Aspirin, Laboratory Biomarker Analysis and Metformin Hydrochloride in people with Recurrent Prostate Carcinoma and Stage I Prostate Cancer, run by Rutgers, The State University of New Jersey at 1 site in United States.
Trial summary
This randomized phase II trial studies how well metformin hydrochloride and aspirin work in treating patients with hormone-dependent prostate cancer that has progressed after surgery or radiation therapy. Read more about this study
- Who is it for?
- Ages 18 years and older, men only
- Conditions the study is for
- Recurrent Prostate Carcinoma, Stage I Prostate Cancer, Stage IIA Prostate Cancer
- What is being tested?
- Aspirin, Laboratory Biomarker Analysis and Metformin Hydrochloride
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 27 participants
- Where
- 1 siteUnited States
- Study dates
- 23 Jun 2015to 1 Dec 2019
- 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
- Patients with histologically proven prostate cancer treated with surgery, radiation, or the combination of surgery and radiation for prostate cancer (metastatic to regional lymph nodes) with resection of the nodes, who now has a rising PSA value after definitive local therapy, and no visible metastatic disease on conventional imaging studies
- Patients must have undergone local treatment via prostatectomy or radiation therapy
- Patients must have PSA progression after local treatment:
- PSA values for patients after surgery (or surgery and salvage/adjuvant radiation) must be greater than or equal to 0.2 ng/mL, determined by two measurements, at least 1 month apart and at least 6 months after prostatectomy
- PSA values for patients after radiation must be greater than or equal to 2.0 ng/ml greater than the nadir achieved after radiation, determined by two measurements at 1 month apart and at least 6 months after the radiation treatment is completed; (patients who received adjuvant or salvage radiation after prostatectomy must have PSA of greater than or equal to 0.2)
- The first two PSA values, along with a third (study baseline) value must all be rising (i.e., there must be an overall rising trajectory, such that the third value cannot be lower than the first value)
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- PSA must be less than 50 ng/mL at study entry
- PSA doubling time using the mkscc.org PSA doubling time calculator must be greater than 4 months
- Baseline bone scan, chest x-ray and computed tomography (CT)/magnetic resonance imaging (MRI) of abdomen/pelvis demonstrating no metastatic disease
- Estimated life expectancy of at least 6 months
- Eastern Cooperative Oncology Group (ECOG) performance status =< 2
- White blood cells (WBC) > 3500/ul
- Absolute neutrophil count (ANC) > 1500/ul
- Hemoglobin > 10 g/dl
- Platelet count > 100,000/ul
- Adequate renal function with estimated glomerular filtration rate (GFR) by Cockcroft Gault of greater than 40 ML per minute
- Total bilirubin must be within 1.5 X the normal institutional limits; if total bilirubin is outside the normal institutional limits, assess direct bilirubin
- The direct bilirubin must be within normal parameters
- Transaminases (serum glutamic oxaloacetic transaminase [SGOT] and/or serum glutamate pyruvate transaminase [SGPT]) must be less than 2.5 X the institutional upper limit of normal
- Patients must have a serum total testosterone level >= 150 ng/dL at the time of enrollment within 4 weeks prior to randomization
- Patients must sign informed consent
Who cannot join
- Serious concomitant systemic disorder that would compromise the safety of the patient or compromise the patient's ability to complete the study, at the discretion of the investigator
- Patients may have received prior androgen deprivation therapy (ADT) in the neoadjuvant, adjuvant and/or salvage setting, but must be off therapy for at least 3 months and have a testosterone level > 150 ng/dl
- Second primary malignancy except most situ carcinoma (e.g. adequately treated non-melanomatous carcinoma of the skin) or other malignancy treated at least 2 years previously with no evidence of recurrence
- Patients with type II diabetes currently already on metformin
- Patients taking aspirin for previously diagnosed cardiovascular disease
- Patients who received aspirin or metformin within the past 28 days
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- Patients taking medications with known interactions with metformin or aspirin
- Patients taking warfarin or platelet inhibitors
- Patients requiring chronic use of nonsteroidal anti-inflammatory drugs (NSAIDS)
- Other concurrent experimental or investigational drugs
- Prior history of lactic acidosis or metabolic acidosis
- Patients with history of gastrointestinal (GI) bleeding and peptic ulcer disease
- Any unstable, serious co-existing medical conditions including but not limited to myocardial infarction, coronary bypass surgery, unstable angina, cardiac arrhythmias, clinically evident congestive heart failure, or cerebrovascular accident within 6 months prior to screening
Trial locations and contacts
1 site in 1 country.
United States1 site
Rutgers Cancer Institute of New Jersey
New Brunswick, New Jersey, 08903
About this study
Official title: A Phase 2 Randomized Discontinuation Trial in Patients With Hormone-Dependent Rising Prostate-Specific Antigen Progression After Local Therapy for Prostate Cancer Evaluating the Synergy of Metformin Plus Aspirin (PRIMA Trial)
This randomized phase II trial studies how well metformin hydrochloride and aspirin work in treating patients with hormone-dependent prostate cancer that has progressed after surgery or radiation therapy. Metformin hydrochloride and aspirin may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. It is not yet known whether giving metformin hydrochloride and aspirin together can slow the growth of prostate cancer.
Read the detailed description
PRIMARY OBJECTIVES:
- To determine the effect of metformin (metformin hydrochloride) and aspirin on the change in prostate-specific antigen (PSA) progression in men with rising PSA after definitive therapy for localized prostate cancer and stable disease during a run-in period with the study regimen.
SECONDARY OBJECTIVES:
- To determine the feasibility and safety of administering metformin and aspirin.
II. To determine the effect of metformin and aspirin on PSA levels and the serum obesity-related prostate cancer (PCa) biomarkers (insulin, insulin-like growth factor [IGF]-1, interleukin [IL]-1beta, IL-6, and tumor necrosis factor [TNF]-alpha).
OUTLINE:
RUN-IN STAGE: Patients receive metformin hydrochloride orally (PO) twice daily (BID) and aspirin PO once daily (QD) for 4 months. Patients with disease progression (PSA increase of > 50% and minimum of 2ng/ml rise in PSA) come off study. Patients achieving disease response (>25% decline in PSA) continue to receive study agents in the absence of disease progression or unacceptable disease. Patients with stable disease continue on to the randomized study regimen.
RANDOMIZATION STAGE: Patients are randomized to 1 of 2 treatment arms.
ARM I: Patients receive metformin hydrochloride PO BID and aspirin PO QD for 6 months in the absence of disease progression or unacceptable toxicity.
ARM II: Patients receive metformin hydrochloride placebo PO BID and aspirin placebo PO QD for 6 months in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up every 12-16 weeks for 1 year.
- Conditions
- Recurrent Prostate Carcinoma, Stage I Prostate Cancer, Stage IIA Prostate Cancer, Stage IIB Prostate Cancer, Stage III Prostate Cancer
- Being tested
- Aspirin, Laboratory Biomarker Analysis, Metformin Hydrochloride, Placebo
- Medical subject headings
- Prostatic Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AspirinDrug
Also called Acetylsalicylic Acid, ASA, Aspergum, Ecotrin
Given PO
Laboratory Biomarker AnalysisOther
Correlative studies
Metformin HydrochlorideDrug
Also called Glucophage, Metformin HCl
Given PO
PlaceboOther
Also called placebo therapy, PLCB, sham therapy
Given metformin hydrochloride placebo PO
PlaceboOther
Also called placebo therapy, PLCB, sham therapy
Given aspirin placebo PO
| Study group | Role | What they receive |
|---|---|---|
| Arm I (metformin hydrochloride, aspirin) | Experimental | Patients receive metformin hydrochloride PO BID and aspirin PO QD for 6 months in the absence of disease progression or unacceptable toxicity. Receives: Drug: Aspirin; Other: Laboratory Biomarker Analysis; Drug: Metformin Hydrochloride |
| Arm II (metformin hydrochloride placebo, aspirin placebo) | Placebo comparator | Patients receive metformin hydrochloride placebo PO BID and aspirin placebo PO QD for 6 months in the absence of disease progression or unacceptable toxicity. Receives: Other: Laboratory Biomarker Analysis; Other: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Measure of PSA ng/mL Rates After Six Months of Metformin Hydrochloride and Aspirin or Placebo Therapy in Patients Who Have Received Four Months of Open Label Treatment
Measured: 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Apr 2015 (estimated)
- Study start23 Jun 2015
- Primary completion1 Dec 2019
- Study completion1 Dec 2019
Why it stopped: Slow accrual
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.
- Other trials for Recurrent Prostate CarcinomaStudies of the same condition, open and under way.
- More trials run by Rutgers, The State University of New JerseyThe 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
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 27 participants (actual)
Sponsor and investigators
- Lead sponsor
- Rutgers, The State University of New Jersey
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI), Rutgers Cancer Institute of New Jersey
- Responsible party
- Principal investigator, Biren Saraiya, MD, Rutgers Cancer Institute of New Jersey
- Investigators
- Biren Saraiya, MD, Principal investigator, Rutgers Cancer Institute of New Jersey
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02420652
- Sponsor's protocol ID
- 081501
- Other IDs
- NCI-2015-00397, Pro20150001378, P30CA072720
- Acronym
- PRIMA
- Status last verified
- Feb 2023
- First submitted
- 15 Apr 2015
- Last updated
- 8 Feb 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 8 Feb 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 2 Randomized Discontinuation Trial in Patients With Hormone-Dependent Rising Prostate-Specific Antigen Progression After Local Therapy for Prostate Cancer Evaluating the Synergy of Metformin Plus Aspirin (PRIMA Trial)
- ClinicalTrials.gov ID
- NCT02420652
- Acronym / sponsor ID
- PRIMA / 081501
- Conditions
- Recurrent Prostate Carcinoma, Stage I Prostate Cancer, Stage IIA Prostate Cancer, Stage IIB Prostate Cancer, Stage III Prostate Cancer
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Slow accrual
- Enrolment
- 27 participants (actual)
- Lead sponsor
- Rutgers, The State University of New JerseyUniversity, hospital or other
- Collaborators
- National Cancer Institute (NCI), Rutgers Cancer Institute of New Jersey
- Study start
- 23 Jun 2015 (actual)
- Primary completion
- 1 Dec 2019 (actual)
- Study completion
- 1 Dec 2019 (actual)
- First posted
- 20 Apr 2015 (estimated)
- Results
- Posted 8 Feb 2023
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This randomized phase II trial studies how well metformin hydrochloride and aspirin work in treating patients with hormone-dependent prostate cancer that has progressed after surgery or radiation therapy. Metformin hydrochloride and aspirin may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. It is not yet known whether giving metformin hydrochloride and aspirin together can slow the growth of prostate cancer.
Detailed description
PRIMARY OBJECTIVES:
- To determine the effect of metformin (metformin hydrochloride) and aspirin on the change in prostate-specific antigen (PSA) progression in men with rising PSA after definitive therapy for localized prostate cancer and stable disease during a run-in period with the study regimen.
SECONDARY OBJECTIVES:
- To determine the feasibility and safety of administering metformin and aspirin.
II. To determine the effect of metformin and aspirin on PSA levels and the serum obesity-related prostate cancer (PCa) biomarkers (insulin, insulin-like growth factor [IGF]-1, interleukin [IL]-1beta, IL-6, and tumor necrosis factor [TNF]-alpha).
OUTLINE:
RUN-IN STAGE: Patients receive metformin hydrochloride orally (PO) twice daily (BID) and aspirin PO once daily (QD) for 4 months. Patients with disease progression (PSA increase of > 50% and minimum of 2ng/ml rise in PSA) come off study. Patients achieving disease response (>25% decline in PSA) continue to receive study agents in the absence of disease progression or unacceptable disease. Patients with stable disease continue on to the randomized study regimen.
RANDOMIZATION STAGE: Patients are randomized to 1 of 2 treatment arms.
ARM I: Patients receive metformin hydrochloride PO BID and aspirin PO QD for 6 months in the absence of disease progression or unacceptable toxicity.
ARM II: Patients receive metformin hydrochloride placebo PO BID and aspirin placebo PO QD for 6 months in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up every 12-16 weeks for 1 year.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Arm I (metformin hydrochloride, aspirin) | Experimental | Drug: Aspirin, Other: Laboratory Biomarker Analysis, Drug: Metformin HydrochloridePatients receive metformin hydrochloride PO BID and aspirin PO QD for 6 months in the absence of disease progression or unacceptable toxicity. |
| Arm II (metformin hydrochloride placebo, aspirin placebo) | Placebo comparator | Other: Laboratory Biomarker Analysis, Other: PlaceboPatients receive metformin hydrochloride placebo PO BID and aspirin placebo PO QD for 6 months 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 (21 listed)
- Patients with histologically proven prostate cancer treated with surgery, radiation, or the combination of surgery and radiation for prostate cancer (metastatic to regional lymph nodes) with resection of the nodes, who now has a rising PSA value after definitive local therapy, and no visible metastatic disease on conventional imaging studies
- Patients must have undergone local treatment via prostatectomy or radiation therapy
- Patients must have PSA progression after local treatment:
- Baseline bone scan, chest x-ray and computed tomography (CT)/magnetic resonance imaging (MRI) of abdomen/pelvis demonstrating no metastatic disease
- Estimated life expectancy of at least 6 months
Key exclusion criteria (13 listed)
- Serious concomitant systemic disorder that would compromise the safety of the patient or compromise the patient's ability to complete the study, at the discretion of the investigator
- Patients may have received prior androgen deprivation therapy (ADT) in the neoadjuvant, adjuvant and/or salvage setting, but must be off therapy for at least 3 months and have a testosterone level > 150 ng/dl
- Second primary malignancy except most situ carcinoma (e.g. adequately treated non-melanomatous carcinoma of the skin) or other malignancy treated at least 2 years previously with no evidence of recurrence
- Patients with type II diabetes currently already on metformin
- Patients taking aspirin for previously diagnosed cardiovascular disease
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 |
|---|---|---|
| AspirinAlso: Acetylsalicylic Acid, ASA, Aspergum, EcotrinGiven PO | Drug | Arm I (metformin hydrochloride, aspirin) |
| Laboratory Biomarker AnalysisCorrelative studies | Other | Arm I (metformin hydrochloride, aspirin), Arm II (metformin hydrochloride placebo, aspirin placebo) |
| Metformin HydrochlorideAlso: Glucophage, Metformin HClGiven PO | Drug | Arm I (metformin hydrochloride, aspirin) |
| PlaceboAlso: placebo therapy, PLCB, sham therapyGiven metformin hydrochloride placebo PO | Other | Arm II (metformin hydrochloride placebo, aspirin placebo) |
| PlaceboAlso: placebo therapy, PLCB, sham therapyGiven aspirin placebo PO | Other | Arm II (metformin hydrochloride placebo, aspirin placebo) |
Primary outcome
Measure of PSA ng/mL Rates After Six Months of Metformin Hydrochloride and Aspirin or Placebo Therapy in Patients Who Have Received Four Months of Open Label Treatment
Time frame: 6 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Feb 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
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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.
Biren Saraiya, MD principal investigator
Rutgers Cancer Institute of New Jersey
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 Aspirin, Laboratory Biomarker Analysis and Metformin Hydrochloride in people with Recurrent Prostate Carcinoma and Stage I Prostate Cancer, run by Rutgers, The State University of New Jersey 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 21 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: stopped early, as of the sponsor's last update on 8 Feb 2023. 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 8 Feb 2023). 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?
Measure of PSA ng/mL Rates After Six Months of Metformin Hydrochloride and Aspirin or Placebo Therapy in Patients Who Have Received Four Months of Open Label Treatment (time frame: 6 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 8 Feb 2023.