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Bicalutamide With or Without Metformin for Biochemical Recurrence in Overweight or Obese Prostate Cancer Patients (BIMET-1)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02614859
Recruitment Status : Recruiting
First Posted : November 25, 2015
Last Update Posted : July 29, 2019
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Fox Chase Cancer Center

Tracking Information
First Submitted Date  ICMJE November 18, 2015
First Posted Date  ICMJE November 25, 2015
Last Update Posted Date July 29, 2019
Actual Study Start Date  ICMJE December 1, 2015
Estimated Primary Completion Date April 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: November 23, 2015)
Biochemical response rate based on PSA [ Time Frame: 32 weeks ]
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT02614859 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: November 23, 2015)
  • Time to PSA progression with metformin plus bicalutamide compared to bicalutamide monotherapy. [ Time Frame: 32 Weeks ]
  • Time to radiographically confirmed disease progression based on RECIST1.1 [ Time Frame: 32 Weeks ]
  • Evaluate Quality of Life based on the Functional Assessment of Cancer Therapy-Prostate (FACT-P) [ Time Frame: Baseline ]
  • Evaluate Quality of Life based on the Functional Assessment of Cancer Therapy-Prostate (FACT-P) [ Time Frame: 32 Weeks ]
  • Number of participants with treatment-related adverse events as assessed by CTCAE v4.0 [ Time Frame: 32 Weeks ]
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Bicalutamide With or Without Metformin for Biochemical Recurrence in Overweight or Obese Prostate Cancer Patients
Official Title  ICMJE Bicalutamide With or Without Metformin for Biochemical Recurrence in Overweight or Obese Prostate Cancer Patients (BIMET-1)
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.
Detailed Description

1 Cycle = 28 days = 4 weeks. Treatment will be administered on an outpatient basis ӿ Metformin starting dose is 500 mg BID, will be gradually increased to target dose of 1000mg BID.

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

Treatment ARM B Cycles 1 - 2: In order to minimize gastrointestinal discomfort, metformin dosing will be ramped up over a period of 2 weeks. Metformin treatment will be started at 500 mg BID (Dose Level -2) and increased by an increment of 500 mg daily every week +/- 2 days provided no grade 2 or higher gastrointestinal toxicity is noted. If grade 2 or greater gastrointestinal toxicity occurs during the first 4 weeks of treatment, the subject will be evaluated every 2 weeks until resolution of toxicity to grade 0 or 1 and, then, the metformin dose will be increased to the next dose level. The target dose of metformin is 1000 mg BID.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Cancer of Prostate
Intervention  ICMJE
  • Drug: Bicalutamide
    Bicalutamide 50 mg daily beginning at cycle 3 to cycle 8
  • Drug: Metformin and Bicalutamide
    Metformin 1000mg twice a day Bicalutamide 50 mg daily beginning at cycle 3
Study Arms  ICMJE
  • Active Comparator: A
    Intervention: Drug: Bicalutamide
  • Experimental: B
    Intervention: Drug: Metformin and Bicalutamide
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: November 23, 2015)
66
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE April 2022
Estimated Primary Completion Date April 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

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.

  1. For radical prostatectomy the threshold for this study is PSA ≥ 0.2ng/mL
  2. 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).
  3. 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

Ability to swallow the study drugs

Subjects must have normal organ and marrow function as defined below:

  1. Absolute neutrophil count greater than or equal to 1,000/mL
  2. Hemoglobin greater than or equal to 10 g/dL
  3. Platelets greater than or equal to 100,000/mL
  4. Total bilirubin within normal institutional limits
  5. AST(SGOT)/ALT(SGPT) less than or equal to 1.5 X institutional ULN
  6. Creatinine clearance greater than or equal to 60 mL/min/1.73 m2
  7. Hgb A1c ≤ 6.5

Exclusion Criteria:

Evidence of metastatic disease on imaging studies (CT and/or bone scan)

Diagnosis of diabetes mellitus defined as

  1. Fasting blood glucose > 126 mg/dl or,
  2. Random blood glucose > 200 mg/dl
  3. 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.

Subjects who have taken 5a-reductase inhibitors (finasteride or dutasteride), saw palmetto, or PC-SPES within the last 6 weeks are ineligible. Subjects will be eligible for the study after the wash out period of 6 weeks.

Sex/Gender  ICMJE
Sexes Eligible for Study: Male
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Daniel Geynisman, MD 215-214-1515 Daniel.Geynisman@fccc.edu
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02614859
Other Study ID Numbers  ICMJE GU-079
15-1015 ( Other Identifier: Fox Chase Cancer Center )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Fox Chase Cancer Center
Study Sponsor  ICMJE Fox Chase Cancer Center
Collaborators  ICMJE National Cancer Institute (NCI)
Investigators  ICMJE
Principal Investigator: Daniel Geynisman, MD Fox Chase Cancer Center
PRS Account Fox Chase Cancer Center
Verification Date July 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP