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

NCT01243385 | Completed Phase 2 DMC

• 3 other identifiers: SAKK 08/09SWS-SAKK-08/09CDR0000688789
• Study Type: interventional
• Target: 44
• Locations: 1 country
• Sites: 9

Brief 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.

Conditions

Prostate Cancer

Keywords

adenocarcinoma of the prostate; hormone-resistant prostate cancer; stage III prostate cancer; stage IV prostate cancer; recurrent prostate cancer

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (8)

• PFS at 24 weeks

  at 24 weeks

• Clinical benefit rate

  at 12 weeks and 24 weeks

• Adverse events

  from start of treatment until progression or death of any cause

• Prostate-specific antigen (PSA) response

  (50% and 30%, best and at 12 weeks)

• Changes in PSA doubling time

  after 12 weeks, after 24 weeks and at best PSA response

Study Arms (1)

Metformin

OTHER

Metformin at a target dose of 2 x 1000 mg daily Until progression, unacceptable toxicity or refusal

Drug: Metformin

Interventions

Metformin DRUG

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

Also known as: Metformin-Mepha

Metformin

Eligibility Criteria

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

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

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• Swiss Cancer Institute: lead

Study Sites (9)

Kantonsspital Aarau

Aarau, CH-5001, Switzerland

Location

Universitaetsspital-Basel

Basel, CH-4031, Switzerland

Location

Inselspital Bern

Bern, CH-3010, Switzerland

Location

Kantonsspital Graubuenden

Chur, CH-7000, Switzerland

Location

Kantonsspital Luzern

Luzerne, CH-6000, Switzerland

Location

Kantonsspital - St. Gallen

Sankt Gallen, CH-9007, Switzerland

Location

Kantonsspital Winterthur

Winterthur, CH-8401, Switzerland

Location

Onkozentrum

Zurich, 8038, Switzerland

Location

UniversitaetsSpital Zuerich

Zurich, CH-8091, Switzerland

Location

Related Publications (1)

• Rothermundt C, Hayoz S, Templeton AJ, Winterhalder R, Strebel RT, Bartschi D, Pollak M, Lui L, Endt K, Schiess R, Ruschoff JH, Cathomas R, Gillessen S. Metformin in chemotherapy-naive castration-resistant prostate cancer: a multicenter phase 2 trial (SAKK 08/09). Eur Urol. 2014 Sep;66(3):468-74. doi: 10.1016/j.eururo.2013.12.057. Epub 2014 Jan 4.

  PMID: 24412228 DERIVED

MeSH Terms

Conditions

Prostatic Neoplasms

Interventions

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)

Biguanides; Guanidines; Amidines; Organic Chemicals

Study Officials

• 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

  STUDY CHAIR

Study Design

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

Study Record Dates

• First Submitted: November 17, 2010
• First Posted: November 18, 2010
• Study Start: December 23, 2010
• Primary Completion: April 17, 2012
• Study Completion: August 9, 2019
• Last Updated: August 13, 2019

Record last verified: 2019-08

Data Sharing

• IPD Sharing: Will not share

Locations

CH (9)