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Metformin Hydrochloride as First-Line Therapy in Treating Patients With Locally Advanced or Metastatic Prostate Cancer

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Swiss Group for Clinical Cancer Research
ClinicalTrials.gov Identifier:
NCT01243385
First received: November 17, 2010
Last updated: May 2, 2017
Last verified: May 2017
  Purpose

RATIONALE: Metformin hydrochloride may make some enzymes active. These enzymes may block other enzymes needed for cell growth and stop the growth of tumor cells.

PURPOSE: This phase II trial is studying the safety of giving metformin hydrochloride as first-line therapy in treating patients with locally advanced or metastatic prostate cancer.


Condition Intervention Phase
Prostate Cancer
Drug: Metformin
Phase 2

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: No masking
Primary Purpose: Treatment
Official Title: Metformin in Castration Resistant Prostate Cancer. A Multicenter Phase II Trial.

Resource links provided by NLM:


Further study details as provided by Swiss Group for Clinical Cancer Research:

Primary Outcome Measures:
  • Progression-free survival (PFS) at 12 weeks [ Time Frame: at 12 weeks ]
    PFS is defined as the absence of disease progression or death at 12 weeks after start of treatment.


Secondary Outcome Measures:
  • PFS at 24 weeks [ Time Frame: at 24 weeks ]
    PFS is defined as the absence of any disease progression or death at 24 weeks after start of treatment

  • Clinical benefit rate [ Time Frame: at 12 weeks and 24 weeks ]
    Clinical benefit is defined as SD by imaging and symptoms - with or without PSA progression

  • Adverse events [ Time Frame: from start of treatment until progression or death of any cause ]
    All AEs will be assessed according to NCI CTCAE v4.0

  • Prostate-specific antigen (PSA) response [ Time Frame: (50% and 30%, best and at 12 weeks) ]

    50 % PSA response is defined as a decrease in PSA level of at least 50 % (compared to baseline PSA).

    30 % PSA response is defined as a decrease in PSA level of at least 30 % (compared to baseline PSA).

    Best response is defined as the percentage of change in PSA from baseline to the maximum decline in PSA at any point under treatment at 12 weeks or later. If there is a steady increase after baseline, the best response is defined as the percentage of change in PSA from baseline to the minimum increase in PSA at any point under treatment at 12 weeks or later.


  • Changes in PSA doubling time [ Time Frame: after 12 weeks, after 24 weeks and at best PSA response ]
    PSA-DT is calculated from the natural log of 2 divided by the slope of the relationship between the log of PSA and the time of PSA measurement for each patient.

  • Tumor response of measurable disease according to RECIST v 1.1 criteria [ Time Frame: after 12 weeks of treatment ]
    For patients with measurable disease at baseline RECIST v1.1 will be used to define CR, PR, SD and PD.

  • Tumor assessment of bone lesions [ Time Frame: at 12 weeks ]
    Bone metastases can be assessed by radionuclide bone scan.

  • Overall survival [ Time Frame: from registration until death ]
    OS will be calculated from registration until death


Estimated Enrollment: 44
Study Start Date: December 2010
Estimated Study Completion Date: September 2017
Estimated Primary Completion Date: September 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Metformin
Metformin at a target dose of 2 x 1000 mg daily Until progression, unacceptable toxicity or refusal
Drug: Metformin
Metformin Lifelong follow-up at a target dose of 2 x 1000 mg daily Until progression, unacceptable toxicity or refusal
Other Name: Metformin-Mepha

Detailed Description:

OBJECTIVES:

  • To determine the activity and safety of metformin hydrochloride as first-line therapy in patients with locally advanced or metastatic castration-resistant prostate cancer.

OUTLINE: This is a multicenter study.

Patients receive oral metformin hydrochloride twice daily on days 1-28. Treatment repeats every 4 weeks in the absence of disease progression or unacceptable toxicity.

Previously collected and post-treatment tumor tissue may be analyzed for PTEN status and PI3kinase-dependent pathway activation via immunohistochemistry. Blood samples may also be collected periodically and analyzed for biomarkers, pharmacogenetics, pharmacodynamics, pharmacokinetics.

After completion of study therapy, patients are followed up every 3 months.

  Eligibility

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

DISEASE CHARACTERISTICS:

  • Histologically confirmed adenocarcinoma of the prostate

    • Locally advanced or metastatic disease with no curative therapy possible
  • PSA progression defined as the following:

    • Increase in PSA of ≥ 25% (and an absolute increase of ≥ 2 ng/mL) over nadir value on hormonal therapy measured on 3 successive occasions at least 1 week apart

      • If the third measurement is not higher than the second, a fourth measurement will be taken and only if the fourth measurement is higher than the second, the patient may be enrolled
  • PSA doubling time ≥ 55 days (if used to define progression, must not be older than 6 months)
  • PSA < 114 ng/mL
  • Testosterone level ≤ 1.7 nmol/L (≤ 50 ng/dL) after at least 1 hormonal treatment (orchiectomy or luteinizing hormone-releasing hormone [LHRH] agonist)
  • Patients who have not undergone surgical castration must continue LHRH agonist therapy during study treatment
  • Oligosymptomatic or asymptomatic in relation to disease
  • No known or suspected CNS metastases

PATIENT CHARACTERISTICS:

  • WHO performance status 0-1
  • Hemoglobin ≥ 90 g/L
  • Neutrophil count ≥ 1.5 x 10^9/L
  • Platelet count ≥ 100 x 10^9/L
  • AST ≤ 2.5 times upper limit of normal (ULN)
  • Bilirubin ≤ 1.5 times ULN
  • Creatinine clearance ≥ 60 mL/min
  • Compliant and geographically proximal for proper staging and follow-up
  • No previous malignancy within the past 2 years except for localized nonmelanoma skin cancer or Ta or Tis bladder cancer
  • No history of diabetic ketoacidosis, diabetic coma, or pre-coma
  • No known history of HIV, hepatitis B, or hepatitis C positivity
  • No known hypersensitivity to the trial drug or any of its components
  • No serious underlying medical condition that, in the judgment of the investigator, would impair the ability of the patient to participate in the trial (e.g., uncontrolled or acute severe infection, uncontrolled diabetes, advanced chronic obstructive pulmonary disease [COPD], or heart failure)
  • No psychiatric disorder precluding understanding of information on trial related topics, giving informed consent, or interfering with compliance for oral drug intake
  • No known alcohol abuse

PRIOR CONCURRENT THERAPY:

  • See Disease Characteristics
  • At least 6 weeks since prior antiandrogen therapy and without withdrawal response
  • At least 30 days since prior treatment in another clinical trial
  • At least 4 weeks since prior major surgery
  • At least 4 weeks since prior products known to affect PSA levels
  • At least 2 weeks since prior local radiation
  • No prior chemotherapy, radioisotopes, small molecules, or immunotherapy for prostate cancer
  • No prior metformin hydrochloride
  • No concurrent pharmacotherapy for diabetes mellitus
  • No concurrent finasteride, dutasteride, ketoconazole, or abiraterone acetate
  • No concurrent corticosteroids with an equivalent dose of > 7.5 mg of prednisolone
  • No concurrent radiotherapy
  • No bisphosphonates started after registration
  • No concurrent drugs contraindicated for use with the trial drug according to the Swissmedic approved product information
  • No other concurrent anticancer drugs
  • No other concurrent experimental or investigational drugs
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01243385

Locations
Switzerland
Kantonsspital Aarau
Aarau, Switzerland, CH-5001
Universitaetsspital-Basel
Basel, Switzerland, CH-4031
Inselspital Bern
Bern, Switzerland, CH-3010
Kantonsspital Graubuenden
Chur, Switzerland, CH-7000
Kantonsspital Luzern
Luzerne, Switzerland, CH-6000
Kantonsspital - St. Gallen
St. Gallen, Switzerland, CH-9007
Kantonsspital Winterthur
Winterthur, Switzerland, CH-8401
Onkozentrum
Zurich, Switzerland, 8038
UniversitaetsSpital Zuerich
Zurich, Switzerland, CH-8091
Sponsors and Collaborators
Swiss Group for Clinical Cancer Research
Investigators
Study Chair: Christian Rothermundt, MD Cantonal Hospital of St. Gallen
Study Chair: Richard Cathomas, MD Kantonsspital Graubuenden
Study Chair: Silke Gillessen, MD Cantonal Hospital of St. Gallen
  More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Swiss Group for Clinical Cancer Research
ClinicalTrials.gov Identifier: NCT01243385     History of Changes
Other Study ID Numbers: SAKK 08/09
SWS-SAKK-08/09
CDR0000688789 ( Other Identifier: CDR0000688789 )
Study First Received: November 17, 2010
Last Updated: May 2, 2017
Individual Participant Data  
Plan to Share IPD: No

Keywords provided by Swiss Group for Clinical Cancer Research:
adenocarcinoma of the prostate
hormone-resistant prostate cancer
stage III prostate cancer
stage IV prostate cancer
recurrent prostate cancer

Additional relevant MeSH terms:
Prostatic Neoplasms
Genital Neoplasms, Male
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
Genital Diseases, Male
Prostatic Diseases
Metformin
Hypoglycemic Agents
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on May 25, 2017