Clinical trials are critical to informing the care of patients with cancer. However, only
3-5% of patients with cancer enroll in clinical trials. Poor accrual to trials has major
implications with regards to the pace of progress, the cost of clinical cancer research, and
the generalizability of results. The investigators have recently shown in an analysis of
7,776 cancer clinical trials registered on clinicaltrials.gov that approximately 20% of
cancer clinical trials fail to complete enrollment at all; the most often cited reason was
Prior research has identified barriers to cancer clinical trial accrual that can be
generally categorized in the domains of availability, awareness, and acceptance. Much
attention has been paid to the barriers involvement awareness and acceptance - however,
trial availability is likely a "rate limiting step". This pilot study is the first in a
series of planned steps to attempt to shift the current paradigm of "bringing patients to
trials" to "bringing trials to patients." With the integration of telemedicine visits, the
investigators aim to decrease the burden of participation for patients, begin to address
geographic barriers, and ultimately improve trial accrual. In this study, men with
biochemically recurrent prostate cancer (a rising PSA after definitive local therapy) will
receive the antidiabetic drug, metformin. Patients will require a single on-site visit for
study enrollment. The remainder of the 6 month study will be conducted via a HIPPA secure
telemonitoring system (monthly visits conducted via telemedicine with tablet computers
provided to each patients).
Men with an isolated PSA recurrence after local therapy are an ideal population for the
evaluation of novel therapies given the minimal disease burden, generally indolent natural
history, and patients' preference to avoid the adverse effects of androgen deprivation
therapy. Metformin has shown anti-prostate cancer activity in preclinical models and cohort
studies. Metformin, a biguanide oral antihyperglycemic agent, abrogates hyperinsulinemia in
individuals with and without diabetes and has shown promising anti-prostate cancer activity
in preclinical models, epidemiologic studies, and retrospective cohorts. Several
epidemiologic/retrospective studies have shown that metformin has a positive impact on
overall survival among men with prostate cancer.
These nonclinical and clinical studies have led to calls for prospective studies of
metformin in patients with prostate cancer. This is a pilot telemedicine study of metformin
in patients with a rising PSA ("biochemical recurrence") after definitive local therapy for
The current study is supported by the following rationale:
- A large proportion of clinical trials close prematurely due to poor accrual.
- Geographic inaccessibility is a barrier to clinical trial participation.
- Metformin is a safe and inexpensive medication that has demonstrated anti-prostate
cancer activity in nonclinical and epidemiologic studies. Importantly, metformin has
been shown to be safe in non-diabetic patients (e.g., patients with polycystic ovary
disease) and does not cause hypoglycemia.
- Use of novel technologies may facilitate clinical trial accrual and minimize the burden
of participation for patients. Ultimately, these approaches may also decrease the cost
of drug development and increase the pace of progress.
In the absence of prohibitive toxicities or disease progression (defined in 4.4), patients
may continue treatment for the 6-month study period. This study will include a baseline
visit for study enrollment at Mount Sinai. The remainder of the visits will be telemedicine
visits conducted using secure video conferencing.
- Histologically confirmed adenocarcinoma of the prostate. (*in situations where
pathology reports documenting prostate cancer are no longer available such as when
the initial biopsy or prostatectomy was performed in the remote past, a documented
history of prior prostate cancer and prostate cancer treatment in prior medical
records will be sufficient)
- Biochemical disease progression after radical prostatectomy and/or radiation therapy
(external-beam radiation therapy and/or brachytherapy), and no radiographic evidence
- Men with history of radical prostatectomy are required to have baseline PSA >
0.5 ng/mL (Prior treatment with neoadjuvant, adjuvant, or salvage radiation
therapy is allowed, again, with screening PSA greater than or equal to 0.5 ng/mL
required for eligibility).
- Men treated with primary radiation therapy are required to have baseline PSA ≥
1.0 ng/mL above their post radiation nadir for men who were treated with primary
radiation therapy (external beam and/or brachytherapy). Men who had primary
radiation therapy followed by salvage prostatectomy are eligible if screening
PSA is greater than or equal to 0.5 ng/mL.
- Men with previous neoadjuvant adjuvant hormone therapy are eligible if
testosterone level at screening is non-castrate (≥ 50 ng/dl). Men previously
treated with intermittent hormonal therapy are also eligible if level of
testosterone at screening is non-castrate (≥ 50 ng/dl).
- Eastern Cooperative Oncology Group (ECOG) performance status less than or equal to 2
(Karnofsky greater than or equal to 60%).
- Subjects must have normal organ as defined below:
- AST(SGOT)/ALT(SGPT) less than or equal to 1.8 X institutional upper limit of
- Serum bilirubin ≤ ULN (except for subjects with Gilbert's Disease who are
eligible despite elevated serum bilirubin level)
- Creatinine ≤ 1.5 mg/dL and/or creatinine clearance > 60 ml/min
- English speaking
- Concurrent use of other investigational agents or other prostate cancer therapies
(e.g., androgen deprivation therapy)
- Currently taking metformin, sulfonylureas, thiazolidinedione, insulin, or other
antidiabetic drugs for any reason.
- Known hypersensitivity or intolerance to metformin
- Condition associated with increased risk of metformin-associated lactic acidosis:
- New York Heart Association Class III or IV Heart Failure
- Intake of 3 or more alcoholic beverages per day
- Known history of lactic acidosis