Prostate Cancer
Conditions
Keywords
castration-resistant prostate cancer, insulin levels, metformin
Brief summary
Metformin is a medication that is prescribed for people with diabetes to help the body respond better to its own insulin and decrease sugar production by the liver. This helps control the body's blood sugar level and is approved by the Food and Drug Administration (FDA) for the treatment of diabetes. Participant's in this research study will already be receiving androgen deprivation therapy (ADT) for prostate cancer. ADT is considered standard of care for prostate cancer. Changes in the participant's metabolism, including changes in insulin and blood sugar levels, are often seen as a result of this type of hormone therapy. Some studies have shown a relationship between insulin and prostate cancer. These studies have suggested that insulin may signal tumor cells to grow. Other studies suggest that people receiving metformin treatment for diabetes may enjoy better outcomes from their prostate cancer then other similar patients who are not treated with metformin.
Detailed description
* Each treatment cycle lasts 4 weeks (28 days). Participants will take metformin twice a day for all 28 days (except for the first 7 days of the first cycle when they will take it just once daily.) * The following procedures will be done on Day 1 of treatment cycles 1, 2, 4, 7 and 10: medical history review, performance status, physical exam, blood tests. * If the participant's first computed tomography (CT) or bone scan at the time of screening showed evidence of cancer, CT and bone scans will be repeated on Day 1 of treatment cycles 4, 7 and 10. * Participants will be in this research study for about 12 months.
Interventions
DRUGMetformin
Taken orally twice daily each 28-day cycle, for 12 cycles
Sponsors
Dana-Farber Cancer Institute
Brigham and Women's Hospital
Beth Israel Deaconess Medical Center
Massachusetts General Hospital
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Healthy volunteers
No
Inclusion criteria
* Histologically or cytologically confirmed adenocarcinoma of the prostate * History of bilateral orchiectomies or ongoing treatment with a GnRH agonist for GnRH antagonist * Disease progression according to PSA Working Group 2 * Minimum starting PSA (Prostate Specific Antigen) level of 2.0 ng/mL * Eastern Cooperative Oncology Group (ECOG) Performance Status 0 or 1
Exclusion criteria
* Symptomatic metastases * Receiving any other agents for the treatment of prostate cancer except gonadotropin releasing hormone (GnRH) agonist or antagonist within the last 30 days * Received any investigational cancer treatment agents within the last 30 days * Prior treatment with docetaxel * History of diabetes requiring drug therapy * Current treatment with metformin or metformin treatment within the last year * History of allergic reaction to metformin * Have uncontrolled intercurrent illness including, but not limited to ongoing or unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements * Serum creatinine 1.5mg/dL or greater * Hepatic impairment * Need for ongoing treatment with cimetidine * History of a different malignancy except for the following circumstances: Individuals with a history of other malignancies are eligible of they have been disease-free for at least 5 years and are deemed by the investigator to be at low risk for recurrence of that malignancy. Individuals with the following cancers are eligible if diagnosed and treated within the past 5 years: basal cell or squamous cell carcinoma of the skin
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| PSA (Prostate Specific Antigen) Response | Approximately 12 weeks | Percent change in PSA from baseline to 12 weeks. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With PSA Response | 12 weeks | PSA response is defined as a 50% decline from baseline confirmed by a second PSA value 4 weeks later. |
| Relationship Between Baseline Metabolomic Profile and PSA Response | 2 years | To determine the plasma metabolomic profiles associated with response to metformin using the Metabolon platform. The Metabolon platform is a proprietary technique of metabolic profiling using mass spectrometry coupled with liquid and/or gas chromatography and robust bioinformatics. The aim is to test the hypothesis that insulin level is a biomarker that predicts activity of metformin therapy for the treatment of castrate-resistant prostate cancer. |
| Percent Maintaining Glycemic Control | 2 years | To describe glycemic control as assessed by hemoglobin A1C. Glycemic control was defined as maintaining fasting plasma glucose levels less than or equal to 130 mg/dL. Plasma glucose levels were measured at baseline (prior to metformin dosing), pre-month 2, pre-month 4, pre-month 7, pre-month 10 and pre-month 13, and/or at off-study visit. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Metformin This is the only arm of this phase 2 open label study
Metformin: Taken orally twice daily each 28-day cycle | 21 |
| Total | 21 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 3 |
| Overall Study | Lack of Efficacy | 17 |
Baseline characteristics
| Characteristic | Metformin |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 13 Participants |
| Age, Categorical Between 18 and 65 years | 8 Participants |
| Age, Continuous | 65.86 years STANDARD_DEVIATION 7.23 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 9 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 12 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 2 Participants |
| Race (NIH/OMB) White | 18 Participants |
| Region of Enrollment United States | 21 participants |
| Sex: Female, Male Female | 0 Participants |
| Sex: Female, Male Male | 21 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 16 / 21 |
| serious Total, serious adverse events | 0 / 21 |
Outcome results
Primary
PSA (Prostate Specific Antigen) Response
Percent change in PSA from baseline to 12 weeks.
Time frame: Approximately 12 weeks
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Metformin | PSA (Prostate Specific Antigen) Response | 161 percentage of baseline PSA |
Secondary
Number of Participants With PSA Response
PSA response is defined as a 50% decline from baseline confirmed by a second PSA value 4 weeks later.
Time frame: 12 weeks
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Metformin | Number of Participants With PSA Response | 0 Participants |
Secondary
Percent Maintaining Glycemic Control
To describe glycemic control as assessed by hemoglobin A1C. Glycemic control was defined as maintaining fasting plasma glucose levels less than or equal to 130 mg/dL. Plasma glucose levels were measured at baseline (prior to metformin dosing), pre-month 2, pre-month 4, pre-month 7, pre-month 10 and pre-month 13, and/or at off-study visit.
Time frame: 2 years
Population: Participants were stratified based on baseline hemoglobin A1c. HbA1c \< 6.0 is considered normal; HbA1c \>/= 6.0 is considered abnormal.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Metformin | Percent Maintaining Glycemic Control | 15 Participants |
| Abnormal Baseline Hemoglobin A1c | Percent Maintaining Glycemic Control | 6 Participants |
Secondary
Relationship Between Baseline Metabolomic Profile and PSA Response
To determine the plasma metabolomic profiles associated with response to metformin using the Metabolon platform. The Metabolon platform is a proprietary technique of metabolic profiling using mass spectrometry coupled with liquid and/or gas chromatography and robust bioinformatics. The aim is to test the hypothesis that insulin level is a biomarker that predicts activity of metformin therapy for the treatment of castrate-resistant prostate cancer.
Time frame: 2 years
Population: Data was not collected for this outcome measure because blood (plasma) samples were never run on the Metabolon platform, as the study was terminated early.