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

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ClinicalTrials.gov Identifier: NCT02614859
Recruitment Status : Recruiting
First Posted : November 25, 2015
Last Update Posted : May 28, 2018
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Fox Chase Cancer Center

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.

Condition or disease Intervention/treatment Phase
Cancer of Prostate Drug: Bicalutamide Drug: Metformin and Bicalutamide Phase 2

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 : Interventional  (Clinical Trial)
Estimated Enrollment : 66 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Bicalutamide With or Without Metformin for Biochemical Recurrence in Overweight or Obese Prostate Cancer Patients (BIMET-1)
Actual Study Start Date : December 1, 2015
Estimated Primary Completion Date : April 2020
Estimated Study Completion Date : April 2022

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Prostate Cancer

Arm Intervention/treatment
Active Comparator: A Drug: Bicalutamide
Bicalutamide 50 mg daily beginning at cycle 3 to cycle 8

Experimental: B Drug: Metformin and Bicalutamide
Metformin 1000mg twice a day Bicalutamide 50 mg daily beginning at cycle 3




Primary Outcome Measures :
  1. Biochemical response rate based on PSA [ Time Frame: 32 weeks ]

Secondary Outcome Measures :
  1. Time to PSA progression with metformin plus bicalutamide compared to bicalutamide monotherapy. [ Time Frame: 32 Weeks ]
  2. Time to radiographically confirmed disease progression based on RECIST1.1 [ Time Frame: 32 Weeks ]
  3. Evaluate Quality of Life based on the Functional Assessment of Cancer Therapy-Prostate (FACT-P) [ Time Frame: Baseline ]
  4. Evaluate Quality of Life based on the Functional Assessment of Cancer Therapy-Prostate (FACT-P) [ Time Frame: 32 Weeks ]
  5. Number of participants with treatment-related adverse events as assessed by CTCAE v4.0 [ Time Frame: 32 Weeks ]


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   No
Criteria

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.


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02614859


Contacts
Contact: Daniel Geynisman, MD 215-214-1515 Daniel.Geynisman@fccc.edu

Locations
United States, Maryland
National Cancer Institute Recruiting
Bethesda, Maryland, United States, 20892-9760
Contact: Marijo Bilusic, MD       marijo.bilusic@nih.gov   
United States, Pennsylvania
Fox Chase Cancer Center - Philadelphia Recruiting
Philadelphia, Pennsylvania, United States, 19111-2497
Sponsors and Collaborators
Fox Chase Cancer Center
National Cancer Institute (NCI)
Investigators
Principal Investigator: Daniel Geynisman, MD Fox Chase Cancer Center

Responsible Party: Fox Chase Cancer Center
ClinicalTrials.gov Identifier: NCT02614859     History of Changes
Other Study ID Numbers: GU-079
15-1015 ( Other Identifier: Fox Chase Cancer Center )
First Posted: November 25, 2015    Key Record Dates
Last Update Posted: May 28, 2018
Last Verified: May 2018

Additional relevant MeSH terms:
Prostatic Neoplasms
Overweight
Recurrence
Genital Neoplasms, Male
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
Genital Diseases, Male
Prostatic Diseases
Body Weight
Signs and Symptoms
Disease Attributes
Pathologic Processes
Metformin
Bicalutamide
Hypoglycemic Agents
Physiological Effects of Drugs
Androgen Antagonists
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Antineoplastic Agents