This study is NOT currently recruiting participants.
Number
18-C-0076
Sponsoring Institute
National Cancer Institute (NCI)
Recruitment Detail
Type: Completed Study; data analyses ongoing Gender: Male Min Age: 18 Years Max Age: 85 Years
Referral Letter Required
No
Population Exclusion(s)
Neonates;Pregnant Women;Fetuses;Children;Female
Keywords
Hypoglycemic Agents; Hormone Antagonists; Androgen Antagonists; Prostatic Diseases
Recruitment Keyword(s)
None
Condition(s)
Prostatic Neoplasms; Overweight; Recurrence; Genital Neoplasms, Male; Urogenital Neoplasms
Investigational Drug(s)
Investigational Device(s)
Intervention(s)
Drug: Bicalutamide Drug: Metformin
Supporting Site
National Cancer Institute
Prostate specific antigen (PSA) is a protein made by cells of the prostate gland. Men with prostate cancer have more PSA in the blood. Biochemical recurrence is when PSA levels rise after prostate cancer treatment. Researchers want to see if a combination of drugs might help treat this. The drugs are metformin and bicalutamide.
Objective:
To compare the effects of metformin and bicalutamide versus bicalutamide alone on lowering PSA levels.
Eligibility:
Adults age 18 and older who were treated for prostate cancer and have rising PSA
Design:
Participants will be screened with
Medical history
Physical exam
Blood and urine tests
Computed tomography scan and/or chest X-ray
Bone scan. A radioactive material will be injected into a vein.
Quality of life questions
The study will last for eight 4-week cycles.
Participants will have another physical exam, medicine review, and blood tests. They may provide a tissue sample.
Participants will be randomly placed in 1 of 2 groups. They will keep a diary of the pills they take.
Group A will be observed for 2 cycles. Starting in cycle 3, they will take 1 tablet of bicalutamide by mouth each day.
Group B will take metformin by mouth twice each day. If tolerated, the dose will increase the first 2 weeks. Starting in cycle 3, they will also take 1 tablet of bicalutamide each day.
Participants will have regular physical exams, blood tests, and questions about their quality of life.
After finishing treatment, participants will have medical monitoring and testing every 4 weeks. They will have follow-up exams every 12 months until they are on study for 5 years.
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INCLUSION CRITERIA: -Ability to understand and the willingness to sign a written informed consent. -Male 18 years or older. -Histologically or cytologically confirmed diagnosis of prostate cancer. -Patient must have had previous treatment with definitive surgery or radiation therapy or cryoablation. -Patient may have prior salvage therapy (surgery, radiation or other local ablative procedures) within 6 months prior to randomization if the intent was for cure. Prophylactic radiotherapy to prevent gynecomastia within 4 weeks prior to randomization is allowed. -BMI > 25 at study entry. -Patient may have had prior neoadjuvant and/or adjuvant therapy (chemotherapy, vaccines or experimental agents) within 4 weeks prior to randomization, if the PSA rise and PSADT were documented after the testosterone level was > 150 ng/dL. -Patients may not have had therapy modulating testosterone levels (such as luteinizing-hormone, releasing-hormone agonists/antagonists and antiandrogens) within 6 months prior to randomization. Agents such as 5 alpha reductase inhibitors, ketoconazole, abiraterone, systemic steroids, or herbal supplements known to decrease PSA levels including any dose of Megestrol acetate, Finasteride (e.g., Saw Palmetto and PC-SPES, African pygeum extract, lycopene, alanine, glutamic acid and glycine, beta-sitosterol, lycopene, nettle root extract, quercitin, Belizian Man Vine extract, mulra puama extract and epimedium extract Campesterol, Betasitosterol, Stigmasterol, Sitostanol and Brassicasterol) are not permitted at any time during the period that the PSA values are being collected. -Patient must have hormone-sensitive prostate cancer as evident by a serum total testosterone level > 150 ng/dL within 12 weeks prior to randomization. -PSA must be < 30 ng/mL at study entry.<TAB> -Patient must have evidence of biochemical failure after primary therapy and subsequent progression. Biochemical failure is declared when the PSA reaches a threshold value after primary treatment and it differs for radical prostatectomy or radiation therapy. --For radical prostatectomy the threshold for this study is PSA greater than or equal to 0.2 ng/mL --For radiation therapy the threshold is a PSA rise of 2 ng/mL above the nadir PSA achieved post radiation with or without hormone therapy (2006 RTGO- ASTRO Consensus definition). --PSA progression requires a PSA rise above the threshold measured at any time point since the threshold was reached. - PSA doubling time between 3 and 9 months. PSA calculation requires at least two consecutive PSA rises (PSA2 and PSA3) above the threshold PSA (at least 3 PSA values); PSA2 and PSA3 must be obtained within 12 months of study entry. All baseline PSAs should be obtained at the same reference lab. Patient's PSA doubling time must be calculated using the following formula PSADT in Days = 0.693 (t)/In (PSA3) In (PSA2) Where t = the number of days between PSA3 and PSA2 In = the natural log PSADT in months = PSADT Iin days divided by 30.4375 -ECOG performance status 0 to 2. -Ability to swallow the study drugs. -Subjects must have normal organ and marrow function as defined below: --Absolute neutrophil count greater than or equal to1,000/mL --Hemoglobin greater than or equal to 10 g/dL --Platelets greater than or equal to 100,000/mL --Total bilirubin within normal institutional limits --AST(SGOT)/ALT(SGPT) less than or equal to 1.5 X institutional ULN --Creatinine clearance greater than or equal to 60 mL/min/1.73 m2 --Hgb A1c less than or equal to 6.5% EXCLUSION CRITERIA: -Evidence of metastatic disease on imaging studies (CT, x-ray, and/or bone scan). -Diagnosis of diabetes mellitus defined as: --Fasting blood glucose > 126 mg/dl or, --Random blood glucose > 200 mg/dl --Hemoglobin A1C > 6.5% -Need for treatment with any conventional modality for prostate cancer (surgery, radiation therapy, and hormonal therapy). -Prior hormonal therapy for recurrent prostate cancer (hormonal therapy given in a neoadjuvant or adjuvant setting and greater than 6 months before entry is acceptable). -Treatment with any investigational drug 30 days prior to randomization. -Radiation therapy within prior 6 months (prophylactic radiotherapy to prevent gynecomastia within 4 weeks prior to randomization is allowed). -Known hypersensitivity to metformin. -Prior history of lactic acidosis. -Any history of myocardial infarction in the past 12 months. -Subjects who consume more than 3 alcoholic beverages per day. -Subjects with serious intercurrent illness, including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or other nonmalignant medical or psychiatric illness that is uncontrolled or whose control may be jeopardized by the complications of this therapy or may limit compliance with the study requirements (at the discretion of the investigator). -Patient with previous or concurrent malignancy. Exceptions are made for patients who meet any of the following conditions: Basal cell or squamous cell carcinoma of the skin or prior malignancy that has been adequately treated and patient has been continuously disease free for greater than or equal to 2 years. -Subjects currently treated with metformin and/or bicalutamide or who have been treated with metformin and/or bicalutamide in the past 6 months. -Subjects who have taken 5a-reductase inhibitors (finasteride or dutasteride), saw palmetto, or PC-SPES within the last 6 weeks are ineligible. Subjects will be eligible for the study after the wash out period of 6 weeks.
-Ability to understand and the willingness to sign a written informed consent.
-Male 18 years or older.
-Histologically or cytologically confirmed diagnosis of prostate cancer.
-Patient must have had previous treatment with definitive surgery or radiation therapy or cryoablation.
-Patient may have prior salvage therapy (surgery, radiation or other local ablative procedures) within 6 months prior to randomization if the intent was for cure. Prophylactic radiotherapy to prevent gynecomastia within 4 weeks prior to randomization is allowed.
-BMI > 25 at study entry.
-Patient may have had prior neoadjuvant and/or adjuvant therapy (chemotherapy, vaccines or experimental agents) within 4 weeks prior to randomization, if the PSA rise and PSADT were documented after the testosterone level was > 150 ng/dL.
-Patients may not have had therapy modulating testosterone levels (such as luteinizing-hormone, releasing-hormone agonists/antagonists and antiandrogens) within 6 months prior to randomization. Agents such as 5 alpha reductase inhibitors, ketoconazole, abiraterone, systemic steroids, or herbal supplements known to decrease PSA levels including any dose of Megestrol acetate, Finasteride (e.g., Saw Palmetto and PC-SPES, African pygeum extract, lycopene, alanine, glutamic acid and glycine, beta-sitosterol, lycopene, nettle root extract, quercitin, Belizian Man Vine extract, mulra puama extract and epimedium extract Campesterol, Betasitosterol, Stigmasterol, Sitostanol and Brassicasterol) are not permitted at any time during the period that the PSA values are being collected.
-Patient must have hormone-sensitive prostate cancer as evident by a serum total testosterone level > 150 ng/dL within 12 weeks prior to randomization.
-PSA must be < 30 ng/mL at study entry.<TAB>
-Patient must have evidence of biochemical failure after primary therapy and subsequent progression. Biochemical failure is declared when the PSA reaches a threshold value after primary treatment and it differs for radical prostatectomy or radiation therapy.
--For radical prostatectomy the threshold for this study is PSA greater than or equal to 0.2 ng/mL
--For radiation therapy the threshold is a PSA rise of 2 ng/mL above the nadir PSA achieved post radiation with or without hormone therapy (2006 RTGO- ASTRO Consensus definition).
--PSA progression requires a PSA rise above the threshold measured at any time point since the threshold was reached.
- PSA doubling time between 3 and 9 months. PSA calculation requires at least two consecutive PSA rises (PSA2 and PSA3) above the threshold PSA (at least 3 PSA values); PSA2 and PSA3 must be obtained within 12 months of study entry. All baseline PSAs should be obtained at the same reference lab. Patient's PSA doubling time must be calculated using the following formula
PSADT in Days = 0.693 (t)/In (PSA3) In (PSA2)
Where t = the number of days between PSA3 and PSA2
In = the natural log
PSADT in months = PSADT Iin days divided by 30.4375
-ECOG performance status 0 to 2.
-Ability to swallow the study drugs.
-Subjects must have normal organ and marrow function as defined below:
--Absolute neutrophil count greater than or equal to1,000/mL
--Hemoglobin greater than or equal to 10 g/dL
--Platelets greater than or equal to 100,000/mL
--Total bilirubin within normal institutional limits
--AST(SGOT)/ALT(SGPT) less than or equal to 1.5 X institutional ULN
--Creatinine clearance greater than or equal to 60 mL/min/1.73 m2
--Hgb A1c less than or equal to 6.5%
EXCLUSION CRITERIA:
-Evidence of metastatic disease on imaging studies (CT, x-ray, and/or bone scan).
-Diagnosis of diabetes mellitus defined as:
--Fasting blood glucose > 126 mg/dl or,
--Random blood glucose > 200 mg/dl
--Hemoglobin A1C > 6.5%
-Need for treatment with any conventional modality for prostate cancer (surgery, radiation therapy, and hormonal therapy).
-Prior hormonal therapy for recurrent prostate cancer (hormonal therapy given in a neoadjuvant or adjuvant setting and greater than 6 months before entry is acceptable).
-Treatment with any investigational drug 30 days prior to randomization.
-Radiation therapy within prior 6 months (prophylactic radiotherapy to prevent gynecomastia within 4 weeks prior to randomization is allowed).
-Known hypersensitivity to metformin.
-Prior history of lactic acidosis.
-Any history of myocardial infarction in the past 12 months.
-Subjects who consume more than 3 alcoholic beverages per day.
-Subjects with serious intercurrent illness, including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or other nonmalignant medical or psychiatric illness that is uncontrolled or whose control may be jeopardized by the complications of this therapy or may limit compliance with the study requirements (at the discretion of the investigator).
-Patient with previous or concurrent malignancy. Exceptions are made for patients who meet any of the following conditions: Basal cell or squamous cell carcinoma of the skin or prior malignancy that has been adequately treated and patient has been continuously disease free for greater than or equal to 2 years.
-Subjects currently treated with metformin and/or bicalutamide or who have been treated with metformin and/or bicalutamide in the past 6 months.
-Subjects who have taken 5a-reductase inhibitors (finasteride or dutasteride), saw palmetto, or PC-SPES within the last 6 weeks are ineligible. Subjects will be eligible for the study after the wash out period of 6 weeks.
Principal Investigator
Referral Contact
For more information: