Bicalutamide With or Without Metformin for Biochemical Recurrence in Overweight or Obese Prostate Cancer Patients

NCT02614859 | Completed Phase 2 Results DMC

• 2 other identifiers: GU-07915-1015
• Study Type: interventional
• Target: 29
• Locations: 1 country
• Sites: 2

Brief Summary

Obesity and metabolic syndrome are prevalent among prostate cancer patients. Having an elevated insulin level in the blood is associated with a shorter median time to cancer progression and median overall survival in patients with an elevated PSA after prior treatment. Androgen deprivation therapy (ADT) with drugs like bicalutamide is frequently used in this patient population,with no proven benefit, which may increase mortality and morbidity.This study evaluates how metformin in combination with bicalutamide affects prostate cancer.

Conditions

Cancer of Prostate

Outcome Measures

Primary Outcomes (1)

• Biochemical Response Rate Based on PSA

  Participants with undetectable PSA after 32 weeks

  32 weeks

Secondary Outcomes (4)

• PSA Decline ≥ 85% at 32 Weeks

  32 Weeks

• PSA Decline

  8 Weeks

• Median PSA Decline

  8 weeks

• BMI Decline After 32 Weeks

  32 Weeks

Study Arms (2)

Observation and Bicalutamide

ACTIVE COMPARATOR

Cycles 1-2: Observation without treatment Cycles 3-8: Bicalutamide 50 mg daily continuously to end of study

Drug: Observation and Bicalutamide

Metformin and Bicalutamide

EXPERIMENTAL

Cycles 1-2: Metformin 1000mg BID Cycles 3-8: Bicalutamide 50 mg daily and Metformin 1000 mg BID

Drug: Metformin and Bicalutamide

Interventions

Observation and Bicalutamide DRUG

Cycles 1 - 2: Observation without treatment Cycles 3 - 8: Bicalutamide 50 mg daily, orally, continuously to the end of study (week 32).

Observation and Bicalutamide

Metformin and Bicalutamide DRUG

Cycles 1-2: Metformin 1000mg BID Cycles 3-8: Bicalutamide 50 mg daily and Metformin 1000 mg BID

Metformin and Bicalutamide

Eligibility Criteria

• Age: 18 Years+
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Ability to understand and the willingness to sign a written informed consent
• Male 18 years or older
• Histologically or cytologically confirmed diagnosis of prostate cancer
• Patient must have had previous treatment with definitive surgery or radiation therapy or cryoablation
• Patient may have prior salvage therapy (surgery, radiation or other local ablative procedures) within 6 months prior to randomization if the intent was for cure.Prophylactic radiotherapy to prevent gynecomastia within 4 weeks prior to randomization is allowed BMI \> 25 at study entry
• Patient may have had prior neoadjuvant and/or adjuvant therapy (chemotherapy, vaccines or experimental agents) within 4 weeks prior to randomization, if the PSA rise and PSADT were documented after the testosterone level was \> 150ng/dL.
• Patient must have hormone-sensitive prostate cancer as evident by a serum total testosterone level \> 150 ng/dL within 12 weeks prior to randomization.
• PSA must be \< 30 ng/mL at study entry
• Patient may not have had therapy modulating testosterone levels (such as luteinizing hormone,releasing-hormone agonists/antagonists and antiandrogens) within 1 year prior to randomization, unless it was in the neoadjuvant and/or adjuvant setting
• Patient must have evidence of biochemical failure after primary therapy and subsequent progression. Biochemical failure is declared when the PSA reaches a threshold value after primary treatment and it differs for radical prostatectomy or radiation therapy.
• For radical prostatectomy the threshold for this study is PSA ≥ 0.2ng/mL
• For radiation therapy the threshold is a PSA rise of 2 ng/mL above the nadir PSA achieved post radiation with or without hormone therapy (2006 RTOG-ASTRO Consensus definition).
• PSA progression requires a PSA rise above the threshold measured at any time point since the threshold was reached.
• PSA doubling time between 3 and 9 months. PSA calculation requires two consecutive PSA rises (PSA2 and PSA3) above the threshold PSA (total 3 PSA values); PSA2 and PSA3 must be obtained within 12 months of study entry. All baseline PSAs should be obtained at the same reference lab. Patient's PSA doubling time must be calculated using the following formula (http://www.mskcc.org/nomograms/prostate/psa doubling-time):
• ECOG performance status less than or equal to 2

You may not qualify if:

• Evidence of metastatic disease on imaging studies (CT and/or bone scan)
• Diagnosis of diabetes mellitus defined as
• Fasting blood glucose \> 126 mg/dl or,
• Random blood glucose \> 200 mg/dl
• Hemoglobin A1C \> 6.5%
• Need for treatment with any conventional modality for prostate cancer (surgery, radiation therapy, and hormonal therapy)
• Prior hormonal therapy for recurrent prostate cancer (hormonal therapy given in a neoadjuvant or adjuvant setting and greater than 6 months before entry is acceptable)
• Treatment within the last 30 days with any investigational drug
• Radiation therapy within prior 6 months (prophylactic radiotherapy to prevent gynecomastia within 4 weeks prior to randomization is allowed)
• Known hypersensitivity to metformin
• Prior history of lactic acidosis
• Any history of myocardial infarction in the past 12 months
• Subjects who consume more than 3 alcoholic beverages per day Subjects with serious intercurrent illness, including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or other nonmalignant medical or psychiatric illness that is uncontrolled or whose control may be jeopardized by the complications of this therapy or may limit compliance with the study requirements (at the discretion of the investigator)
• Patient with previous or concurrent malignancy. Exceptions are made for patients who meet any of the following conditions: Basal cell or squamous cell carcinoma of the skin or prior malignancy that has been adequately treated and patient has been continuously disease free for ≥ 2 years.
• Subjects currently treated with metformin and/or bicalutamide or who have been treated with metformin and/or bicalutamide in the past 6 months.

Sponsors & Collaborators

• Fox Chase Cancer Center: lead

Study Sites (2)

National Cancer Institute

Bethesda, Maryland, 20892-9760, United States

Location

Fox Chase Cancer Center - Philadelphia

Philadelphia, Pennsylvania, 19111-2497, United States

Location

Related Publications (1)

• Bilusic M, Toney NJ, Donahue RN, Wroblewski S, Zibelman M, Ghatalia P, Ross EA, Karzai F, Madan RA, Dahut WL, Gulley JL, Schlom J, Plimack ER, Geynisman DM. A randomized phase 2 study of bicalutamide with or without metformin for biochemical recurrence in overweight or obese prostate cancer patients (BIMET-1). Prostate Cancer Prostatic Dis. 2022 Apr;25(4):735-740. doi: 10.1038/s41391-022-00492-y. Epub 2022 Jan 25.

  PMID: 35079115 RESULT

MeSH Terms

Conditions

Prostatic Neoplasms

Interventions

Observation; bicalutamide; Metformin

Condition Hierarchy (Ancestors)

Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Methods; Investigative Techniques; Biguanides; Guanidines; Amidines; Organic Chemicals

Results Point of Contact

• Title: Dr. Daniel Geynisman
• Organization: Fox Chase Cancer Center

Daniel.Geynisman@fccc.edu

215-728-3889

Study Officials

• Daniel Geynisman, MD

  Fox Chase Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 18, 2015
• First Posted: November 25, 2015
• Study Start: December 1, 2015
• Primary Completion: January 24, 2020
• Study Completion: January 24, 2020
• Last Updated: March 29, 2022
• Results First Posted: March 29, 2022

Record last verified: 2022-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)