Clinical trial NCT02376166: Metformin for Rising PSA Remote Trial
Official title: M-RePoRT: Metformin - Rising PSA Remote Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Prostate Cancer
Keywords: Prostate Cancer
Lead sponsor: Icahn School of Medicine at Mount Sinai
Sponsor class: OTHER
First posted: 2015-03-03
Enrollment: 15
Sex: MALE
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: OTHER

Brief summary: 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 poor accrual.

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).

Detailed description: 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 prostate cancer.

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.

Eligibility criteria: Inclusion Criteria:

* 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 of metastases.

  * 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 normal
  * 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

Exclusion Criteria:

* 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

Primary outcomes:
measure: Number of Participants That Completed All Telemedicine Visits
timeFrame: 6 months
Secondary outcomes:
measure: Percentage of Participants With Stable PSA Levels at 6 Months as Defined by a <20% Change
timeFrame: baseline and 6 month
measure: Adherence With Metformin as Measured by Electronic Pill Adherence Monitoring
timeFrame: 6 months
measure: Patient Satisfaction as Measured by a Patient Satisfaction Survey Question 1
timeFrame: 6 months
measure: Patient Satisfaction as Measured by a Patient Satisfaction Survey Question 2
timeFrame: 6 months
measure: Patient Satisfaction as Measured by a Patient Satisfaction Survey Question 3
timeFrame: 6 months
measure: Patient Satisfaction as Measured by a Patient Satisfaction Survey Question 4
timeFrame: 6 months
measure: Patient Satisfaction as Measured by a Patient Satisfaction Survey Question 5
timeFrame: 6 months
measure: Patient Satisfaction as Measured by a Patient Satisfaction Survey Question 6
timeFrame: 6 months
measure: Patient Satisfaction as Measured by a Patient Satisfaction Survey Question 7
timeFrame: 6 months
measure: Patient Satisfaction as Measured by a Patient Satisfaction Survey Question 8
timeFrame: 6 months
measure: Patient Satisfaction as Measured by a Patient Satisfaction Survey Question 9
timeFrame: 6 months
measure: Patient Satisfaction as Measured by a Patient Satisfaction Survey Question 10
timeFrame: 6 months
measure: Patient Satisfaction as Measured by a Patient Satisfaction Survey Question 11
timeFrame: 6 months
measure: Patient Satisfaction as Measured by a Patient Satisfaction Survey Question 12
timeFrame: 6 months
measure: Urgency to Have a Bowel Movement Episodes
timeFrame: 6 months
measure: Increased Frequency of Bowel Movements
timeFrame: 6 months
measure: Episodes of Watery Bowel Movements
timeFrame: 6 months
measure: Episodes of Flatulence
timeFrame: 6 months
measure: Episodes of Bloating
timeFrame: 6 months
measure: Episodes of Nausea
timeFrame: 6 months
measure: Episodes of Vomiting
timeFrame: 6 months
Other outcomes:
Locations:
city: New York
country: United States
facility: Icahn School of Medicine at Mount Sinai
state: New York
Study officials:
affiliation: Icahn School of Medicine at Mount Sinai
name: Matthew Galsky, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Galsky MD, Shahin M, Jia R, Shaffer DR, Gimpel-Tetra K, Tsao CK, Baker C, Leiter A, Holland J, Sablinski T, Mehrazin R, Sfakianos JP, Acon P, Oh WK. Telemedicine-Enabled Clinical Trial of Metformin in Patients With Prostate Cancer. JCO Clin Cancer Inform. 2017 Nov;1:1-10. doi: 10.1200/CCI.17.00044.