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

Prostate Cancer Clinical Trial

Official title:

Metformin in Castration Resistant Prostate Cancer. A Multicenter Phase II Trial.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01243385
• Other study ID #: SAKK 08/09
• Secondary ID: SWS-SAKK-08/09CD
• Status: Completed
• Phase: Phase 2
• Start date: December 23, 2010
• Est. completion date: August 9, 2019

Study information

• Verified date: August 2019
• Source: Swiss Group for Clinical Cancer Research
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 44
• Est. completion date: August 9, 2019
• Est. primary completion date: April 17, 2012
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Prostate Cancer
• Prostatic Neoplasms

Intervention

Drug:
• Metformin
Metformin Lifelong follow-up at a target dose of 2 x 1000 mg daily Until progression, unacceptable toxicity or refusal

Locations

Country	Name	City	State
Switzerland	Kantonsspital Aarau	Aarau
Switzerland	Universitaetsspital-Basel	Basel
Switzerland	Inselspital Bern	Bern
Switzerland	Kantonsspital Graubuenden	Chur
Switzerland	Kantonsspital Luzern	Luzerne
Switzerland	Kantonsspital - St. Gallen	St. Gallen
Switzerland	Kantonsspital Winterthur	Winterthur
Switzerland	Onkozentrum	Zurich
Switzerland	UniversitaetsSpital Zuerich	Zurich

Sponsors (1)

Lead Sponsor	Collaborator
Swiss Group for Clinical Cancer Research

Country where clinical trial is conducted

Switzerland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression-free survival (PFS) at 12 weeks	PFS is defined as the absence of disease progression or death at 12 weeks after start of treatment.	at 12 weeks
Secondary	PFS at 24 weeks	PFS is defined as the absence of any disease progression or death at 24 weeks after start of treatment	at 24 weeks
Secondary	Clinical benefit rate	Clinical benefit is defined as SD by imaging and symptoms - with or without PSA progression	at 12 weeks and 24 weeks
Secondary	Adverse events	All AEs will be assessed according to NCI CTCAE v4.0	from start of treatment until progression or death of any cause
Secondary	Prostate-specific antigen (PSA) response	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.	(50% and 30%, best and at 12 weeks)
Secondary	Changes in PSA doubling time	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.	after 12 weeks, after 24 weeks and at best PSA response
Secondary	Tumor response of measurable disease according to RECIST v 1.1 criteria	For patients with measurable disease at baseline RECIST v1.1 will be used to define CR, PR, SD and PD.	after 12 weeks of treatment
Secondary	Tumor assessment of bone lesions	Bone metastases can be assessed by radionuclide bone scan.	at 12 weeks
Secondary	Overall survival	OS will be calculated from registration until death	from registration until death