Trial Outcomes & Findings for Castration Compared to Castration Plus Metformin as First Line Treatment for Patients With Advanced Prostate Cancer (NCT NCT01620593)

Results Overview

Compare both cohorts of castrated men (metformin vs. placebo) with regard to metabolic consequences of castration therapy:change in weight.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

41 participants

Primary outcome timeframe

Change from 0 weeks to 28 weeks

Results posted on

2018-05-23

Participant Flow

Participant milestones

Participant milestones
Measure	Placebo and Castration Metabolic consequences including development of hyperinsulinemia and insulin resistance using metformin compared to placebo in men on castration therapy. Placebo and Castration: All eligible subjects will be randomized in a 1:l manner to receive a bottle containing sufficient 500mg tablets of metformin or placebo, blinded to the patient and the study team.	Metformin and Castration Metabolic consequences including development of hyperinsulinemia and insulin resistance using metformin compared to placebo in men on castration therapy. In the rare case where a patient may not tolerate 500 mg three times a day, he may remain on the study taking only 500 mg twice a day. Metformin and Castration: All eligible subjects will be randomized in a 1:l manner to receive a bottle containing sufficient500mg tablets of metformin or placebo, blinded to the patient and the study team.
Overall Study STARTED	21	20
Overall Study COMPLETED	17	19
Overall Study NOT COMPLETED	4	1

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Castration Compared to Castration Plus Metformin as First Line Treatment for Patients With Advanced Prostate Cancer

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo and Castration n=17 Participants Metabolic consequences including development of hyperinsulinemia and insulin resistance using metformin compared to placebo in men on castration therapy. Placebo and Castration: All eligible subjects will be randomized in a 1:l manner to receive a bottle containing sufficient 500mg tablets of metformin or placebo, blinded to the patient and the study team.	Metformin and Castration n=19 Participants Metabolic consequences including development of hyperinsulinemia and insulin resistance using metformin compared to placebo in men on castration therapy. In the rare case where a patient may not tolerate 500 mg three times a day, he may remain on the study taking only 500 mg twice a day. Metformin and Castration: All eligible subjects will be randomized in a 1:l manner to receive a bottle containing sufficient500mg tablets of metformin or placebo, blinded to the patient and the study team.	Total n=36 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	17 Participants n=5 Participants	19 Participants n=7 Participants	36 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Sex: Female, Male Female	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Sex: Female, Male Male	17 Participants n=5 Participants	19 Participants n=7 Participants	36 Participants n=5 Participants
Region of Enrollment United States	17 Participants n=5 Participants	19 Participants n=7 Participants	36 Participants n=5 Participants

PRIMARY outcome

Timeframe: Change from 0 weeks to 28 weeks

Population: Only subjects that completed the study were analyzed

Compare both cohorts of castrated men (metformin vs. placebo) with regard to metabolic consequences of castration therapy:change in weight.

Outcome measures

Outcome measures
Measure	Placebo and Castration n=17 Participants Metabolic consequences including development of hyperinsulinemia and insulin resistance using metformin compared to placebo in men on castration therapy. Placebo and Castration: All eligible subjects will be randomized in a 1:l manner to receive a bottle containing sufficient 500mg tablets of metformin or placebo, blinded to the patient and the study team.	Metformin and Castration n=19 Participants Metabolic consequences including development of hyperinsulinemia and insulin resistance using metformin compared to placebo in men on castration therapy. In the rare case where a patient may not tolerate 500 mg three times a day, he may remain on the study taking only 500 mg twice a day. Metformin and Castration: All eligible subjects will be randomized in a 1:l manner to receive a bottle containing sufficient500mg tablets of metformin or placebo, blinded to the patient and the study team.
Metabolic Syndrome	0 kilograms Interval 0.0 to 0.0	0 kilograms Interval 0.0 to 0.0

PRIMARY outcome

Timeframe: Change from 12 to 28 weeks

Compare both cohorts of castrated men (metformin vs. placebo) with regard to metabolic consequences of castration therapy:change in waist circumference.

Outcome measures

Outcome measures
Measure	Placebo and Castration n=17 Participants Metabolic consequences including development of hyperinsulinemia and insulin resistance using metformin compared to placebo in men on castration therapy. Placebo and Castration: All eligible subjects will be randomized in a 1:l manner to receive a bottle containing sufficient 500mg tablets of metformin or placebo, blinded to the patient and the study team.	Metformin and Castration n=19 Participants Metabolic consequences including development of hyperinsulinemia and insulin resistance using metformin compared to placebo in men on castration therapy. In the rare case where a patient may not tolerate 500 mg three times a day, he may remain on the study taking only 500 mg twice a day. Metformin and Castration: All eligible subjects will be randomized in a 1:l manner to receive a bottle containing sufficient500mg tablets of metformin or placebo, blinded to the patient and the study team.
Metabolic Syndrome Waist Circumference	40.52 centimeters Interval 29.5 to 47.5	41.14 centimeters Interval 30.25 to 50.0

SECONDARY outcome

Timeframe: 28 weeks

Complete Response for PSA measure was defined as a PSA less than or equal to 4 ng/ml or undetectable value at 7 months.

Outcome measures

Outcome measures
Measure	Placebo and Castration n=17 Participants Metabolic consequences including development of hyperinsulinemia and insulin resistance using metformin compared to placebo in men on castration therapy. Placebo and Castration: All eligible subjects will be randomized in a 1:l manner to receive a bottle containing sufficient 500mg tablets of metformin or placebo, blinded to the patient and the study team.	Metformin and Castration n=19 Participants Metabolic consequences including development of hyperinsulinemia and insulin resistance using metformin compared to placebo in men on castration therapy. In the rare case where a patient may not tolerate 500 mg three times a day, he may remain on the study taking only 500 mg twice a day. Metformin and Castration: All eligible subjects will be randomized in a 1:l manner to receive a bottle containing sufficient500mg tablets of metformin or placebo, blinded to the patient and the study team.
PSA Response	58.2 ng/ml Standard Deviation 193.43	8.36 ng/ml Standard Deviation 18.35

SECONDARY outcome

Timeframe: 1 year

Population: Outcome was not measured

Progression time from randomization to the earliest disease progression defined as an increase of 20% or more as per RECIST criteria. Patients will not be removed from protocol treatment for PSA progression alone in the first 12 weeks on this study. Further rise in PSA even in the absence of deterioration of pre-existing lesions will constitute treatment failure. Adverse event leading to withdrawal related to metformin or placebo or castration treatment. Death from any cause. Patients unwillingness to continue. Patient's non-compliance with taking the study intervention - 50% or higher.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 1 year

The safety and tolerability of metformin with castration therapy as compared to castration therapy alone as measured by the number of subjects experiencing adverse events using CTCAE (common terminology criteria for adverse events) version 4 criteria. Grades are assigned to each adverse event where: Grade 1 is mild symptoms Grade 2 is moderate symptoms Grade 3 is severe or medically significant but not immediately life-threatening symptoms Grade 4 is life-threatening consequences, where urgent intervention is indicated Grade 5 is death related to the adverse event

Outcome measures

Outcome measures
Measure	Placebo and Castration n=17 Participants Metabolic consequences including development of hyperinsulinemia and insulin resistance using metformin compared to placebo in men on castration therapy. Placebo and Castration: All eligible subjects will be randomized in a 1:l manner to receive a bottle containing sufficient 500mg tablets of metformin or placebo, blinded to the patient and the study team.	Metformin and Castration n=19 Participants Metabolic consequences including development of hyperinsulinemia and insulin resistance using metformin compared to placebo in men on castration therapy. In the rare case where a patient may not tolerate 500 mg three times a day, he may remain on the study taking only 500 mg twice a day. Metformin and Castration: All eligible subjects will be randomized in a 1:l manner to receive a bottle containing sufficient500mg tablets of metformin or placebo, blinded to the patient and the study team.
Number of Participants With Adverse Events Greater than or equal to 1 adverse event	0 Participants	2 Participants
Number of Participants With Adverse Events Adverse event leading to treatment dose reduction	0 Participants	7 Participants

Adverse Events

Placebo and Castration

Serious events: 0 serious events

Other events: 2 other events

Deaths: 0 deaths

Metformin and Castration

Serious events: 0 serious events

Other events: 8 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	Placebo and Castration n=17 participants at risk Metabolic consequences including development of hyperinsulinemia and insulin resistance using metformin compared to placebo in men on castration therapy. Placebo and Castration: All eligible subjects will be randomized in a 1:l manner to receive a bottle containing sufficient 500mg tablets of metformin or placebo, blinded to the patient and the study team.	Metformin and Castration n=19 participants at risk Metabolic consequences including development of hyperinsulinemia and insulin resistance using metformin compared to placebo in men on castration therapy. In the rare case where a patient may not tolerate 500 mg three times a day, he may remain on the study taking only 500 mg twice a day. Metformin and Castration: All eligible subjects will be randomized in a 1:l manner to receive a bottle containing sufficient500mg tablets of metformin or placebo, blinded to the patient and the study team.
Gastrointestinal disorders Diarrhea	5.9% 1/17 • Number of events 1	15.8% 3/19 • Number of events 3
Musculoskeletal and connective tissue disorders Muscle Pain	0.00% 0/17	5.3% 1/19 • Number of events 1
Gastrointestinal disorders Nausea	0.00% 0/17	15.8% 3/19 • Number of events 3
Renal and urinary disorders Increased Creatinine	5.9% 1/17 • Number of events 1	5.3% 1/19 • Number of events 1

Additional Information

Sukeshi Arora, MD

UT Health San Antonio Cancer Center

Phone: 210-450-1015

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place