Metformin for Rising PSA Remote Trial

Prostate Cancer Clinical Trial

— M-RePoRT  

Official title:

M-RePoRT: Metformin - Rising PSA Remote Trial

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02376166
• Other study ID #: GCO 14-0472
• Status: Completed
• Phase: N/A
• First received: February 24, 2015
• Last updated: November 27, 2017
• Start date: July 2014
• Est. completion date: December 2016

Study information

• Verified date: November 2017
• Source: Icahn School of Medicine at Mount Sinai
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 15
• Est. completion date: December 2016
• Est. primary completion date: December 2016
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Male
• Age group: N/A and older

Eligibility

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

Related Conditions & MeSH terms

• Prostate Cancer
• Prostatic Neoplasms

Intervention

Drug:
• Metformin
850 mg PO twice daily for the remainder of the study period (the dose of metformin will be increased to the 850 mg PO twice daily dose in the absence of grade > 1 toxicities)

Locations

Country	Name	City	State
United States	Icahn School of Medicine at Mount Sinai	New York	New York

Sponsors (1)

Lead Sponsor	Collaborator
Matthew Galsky

Country where clinical trial is conducted

United States, 

References & Publications (1)

Telemedicine-Enabled Clinical Trial of Metformin in Patients With Prostate Cancer Galsky M, Shahin M, Jia R, Shaffer D, Gimpel-Tetra K, Tsao C, Baker C, Leiter A, Holland J, Sablinski T, Mehrazin R, Sfakianos J, Acon P, and Oh W. JCO Clinical Cancer Infor

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants That Completed All Telemedicine Visits	Feasibility will be defined as completion of all telemedicine visits by > 2/3 of enrolled patients (unless treatment discontinued early for toxicity or disease progression).	6 months
Secondary	Percentage of Participants With Stable PSA Levels at 6 Months as Defined by a <20% Change	Percent of patients with 6-month PSA stable 20% change at 6 months as compared to baseline	baseline and 6 month
Secondary	Adherence With Metformin as Measured by Electronic Pill Adherence Monitoring	Adherence with metformin as measured by electronic pill adherence monitoring. Patients were provided with an electronic medication dispenser/medication adherence monitoring device. The device provided audible and visual reminders to proceed with drug dosing and was equipped with a cellular modem that registers a signal to a cloud-based database each time a patient accessed his or her study medication. However, the size and shape of the metformin pills caused the device to malfunction frequently, which led patients to access the pills from the device manually; the data, therefore, could not be used for analysis.	6 months
Secondary	Patient Satisfaction as Measured by a Patient Satisfaction Survey Question 1	Patient satisfaction with the remote clinical trial experience as measured by a patient satisfaction survey - "I would participate in a clinical trial in the future".	6 months
Secondary	Patient Satisfaction as Measured by a Patient Satisfaction Survey Question 2	Patient satisfaction with the remote clinical trial experience as measured by a patient satisfaction survey - "I would participate in a telemedicine clinical trial in the future".	6 months
Secondary	Patient Satisfaction as Measured by a Patient Satisfaction Survey Question 3	Patient satisfaction with the remote clinical trial experience as measured by a patient satisfaction survey - "The time commitment required for participation in this trial was not overly burdensome".	6 months
Secondary	Patient Satisfaction as Measured by a Patient Satisfaction Survey Question 4	Patient satisfaction with the remote clinical trial experience as measured by a patient satisfaction survey - "Participation in this trial did not disrupt my work or other activities".	6 months
Secondary	Patient Satisfaction as Measured by a Patient Satisfaction Survey Question 5	Patient satisfaction with the remote clinical trial experience as measured by a patient satisfaction survey - "I found it easy to use the telemonitoring tablet computer".	6 months
Secondary	Patient Satisfaction as Measured by a Patient Satisfaction Survey Question 6	Patient satisfaction with the remote clinical trial experience as measured by a patient satisfaction survey - "This telemedicine approach eases the travel burden for participation in clinical trials for patients".	6 months
Secondary	Patient Satisfaction as Measured by a Patient Satisfaction Survey Question 7	Patient satisfaction with the remote clinical trial experience as measured by a patient satisfaction survey - "This telemedicine approach eases the financial burden of participation in clinical trials for patients".	6 months
Secondary	Patient Satisfaction as Measured by a Patient Satisfaction Survey Question 8	Patient satisfaction with the remote clinical trial experience as measured by a patient satisfaction survey - "My local physician was adequately informed about my participation in this trial (if applicable)".	6 months
Secondary	Patient Satisfaction as Measured by a Patient Satisfaction Survey Question 9	Patient satisfaction with the remote clinical trial experience as measured by a patient satisfaction survey - "I felt I was monitored sufficiently closely while enrolled in this trial".	6 months
Secondary	Patient Satisfaction as Measured by a Patient Satisfaction Survey Question 10	Patient satisfaction with the remote clinical trial experience as measured by a patient satisfaction survey - "I would recommend participation in a telemedicine clinical trial to other patients".	6 months
Secondary	Patient Satisfaction as Measured by a Patient Satisfaction Survey Question 11	Patient satisfaction with the remote clinical trial experience as measured by a patient satisfaction survey - "I would participate in a clinical trial where the entire trial was conducted remotely without requiring any visits to the study center".	6 months
Secondary	Patient Satisfaction as Measured by a Patient Satisfaction Survey Question 12	Patient satisfaction with the remote clinical trial experience as measured by a patient satisfaction survey - "I felt that I was able to communicate well with the study team, even though most contact was through the tablet computer video instead of in person".	6 months
Secondary	Urgency to Have a Bowel Movement Episodes	Quality of LIfe as measured by a modified RAND 36-Item Health Survey. Ist reported outcome - Number of episodes of urgency to have a bowel movement	6 months
Secondary	Increased Frequency of Bowel Movements	Quality of LIfe as measured by a modified RAND 36-Item Health Survey. Ist reported outcome - Number of episodes of Increased frequency of bowel movements	6 months
Secondary	Episodes of Watery Bowel Movements	Quality of LIfe as measured by a modified RAND 36-Item Health Survey. 2st reported outcome - Number of episodes of watery bowel movements	6 months
Secondary	Episodes of Flatulence	Quality of LIfe as measured by a modified RAND 36-Item Health Survey. 3rd reported outcome - Number of episodes of flatulence	6 months
Secondary	Episodes of Bloating	Quality of LIfe as measured by a modified RAND 36-Item Health Survey. 4th reported outcome - Number of episodes of bloating	6 months
Secondary	Episodes of Nausea	Quality of LIfe as measured by a modified RAND 36-Item Health Survey. 5th reported outcome - Number of episodes of nausea	6 months
Secondary	Episodes of Vomiting	Quality of LIfe as measured by a modified RAND 36-Item Health Survey. 6th reported outcome - Number of episodes of vomiting	6 months