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Metformin Hydrochloride and Aspirin in Treating Patients With Hormone-Dependent Prostate Cancer That Has Progressed After Surgery or Radiation Therapy (PRIMA)

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: NCT02420652
Recruitment Status : Active, not recruiting
First Posted : April 20, 2015
Last Update Posted : May 22, 2019
Sponsor:
Collaborators:
National Cancer Institute (NCI)
Rutgers Cancer Institute of New Jersey
Information provided by (Responsible Party):
Rutgers, The State University of New Jersey

Brief 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. 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.

Condition or disease Intervention/treatment Phase
Recurrent Prostate Carcinoma Stage I Prostate Cancer Stage IIA Prostate Cancer Stage IIB Prostate Cancer Stage III Prostate Cancer Drug: Aspirin Other: Laboratory Biomarker Analysis Drug: Metformin Hydrochloride Other: Placebo Phase 2

Detailed Description:

PRIMARY OBJECTIVES:

I. 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:

I. 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.


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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 27 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
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)
Actual Study Start Date : June 23, 2015
Actual Primary Completion Date : January 8, 2018
Estimated Study Completion Date : January 1, 2020

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Arm I (metformin hydrochloride, aspirin)
Patients receive metformin hydrochloride PO BID and aspirin PO QD for 6 months in the absence of disease progression or unacceptable toxicity.
Drug: Aspirin
Given PO
Other Names:
  • Acetylsalicylic Acid
  • ASA
  • Aspergum
  • Ecotrin
  • Empirin
  • Entericin
  • Extren
  • Measurin

Other: Laboratory Biomarker Analysis
Correlative studies

Drug: Metformin Hydrochloride
Given PO
Other Names:
  • Glucophage
  • Metformin HCl

Placebo Comparator: Arm II (metformin hydrochloride placebo, aspirin placebo)
Patients receive metformin hydrochloride placebo PO BID and aspirin placebo PO QD for 6 months in the absence of disease progression or unacceptable toxicity.
Other: Laboratory Biomarker Analysis
Correlative studies

Other: Placebo
Given metformin hydrochloride placebo PO
Other Names:
  • placebo therapy
  • PLCB
  • sham therapy

Other: Placebo
Given aspirin placebo PO
Other Names:
  • placebo therapy
  • PLCB
  • sham therapy




Primary Outcome Measures :
  1. Change in stable PSA rates after 6 months of metformin hydrochloride and aspirin or placebo therapy in patients who have received 4 months of open label treatment [ Time Frame: Baseline to up to 6 months ]


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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)
    • 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

Exclusion Criteria:

  • 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
  • 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

Information from the National Library of Medicine

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): NCT02420652


Locations
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United States, New Jersey
Rutgers Cancer Institute of New Jersey
New Brunswick, New Jersey, United States, 08903
Sponsors and Collaborators
Rutgers, The State University of New Jersey
National Cancer Institute (NCI)
Rutgers Cancer Institute of New Jersey
Investigators
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Principal Investigator: Biren Saraiya, MD Rutgers Cancer Institute of New Jersey

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Responsible Party: Rutgers, The State University of New Jersey
ClinicalTrials.gov Identifier: NCT02420652     History of Changes
Other Study ID Numbers: 081501
NCI-2015-00397 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
081501 ( Other Identifier: Rutgers Cancer Institute of New Jersey )
P30CA072720 ( U.S. NIH Grant/Contract )
First Posted: April 20, 2015    Key Record Dates
Last Update Posted: May 22, 2019
Last Verified: May 2019

Additional relevant MeSH terms:
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Prostatic Neoplasms
Genital Neoplasms, Male
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
Metformin
Genital Diseases, Male
Prostatic Diseases
Hormones
Aspirin
Hypoglycemic Agents
Physiological Effects of Drugs
Hormones, Hormone Substitutes, and Hormone Antagonists
Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Anti-Inflammatory Agents
Antirheumatic Agents
Fibrinolytic Agents
Fibrin Modulating Agents
Molecular Mechanisms of Pharmacological Action
Platelet Aggregation Inhibitors
Cyclooxygenase Inhibitors
Enzyme Inhibitors
Antipyretics