Repurposing Metformin as Anticancer Drug: in Advanced Prostate Cancer

NCT03137186 | Unknown Phase 2 DMC FDA Drug

• 1 other identifier: Mansmed trial I
• Study Type: interventional
• Target: 120
• Locations: 1 country
• Sites: 1

Brief Summary

This study evaluate the addition of metformin to standard of care in locally advanced and metastatic prostate cancer, half the patient will receive metformin in combination with standard treatment, and the other half will receive the standard of care only

Conditions

Prostate Cancer

Keywords

Metformin, prostate cancer

Outcome Measures

Primary Outcomes (1)

• duration in months from beginning of treatment till development of CRPC

  time till development of CRPC \[Castrate resistant prostate cancer\], is defined by disease progression despite androgen depletion therapy (ADT) and may present as either a continuous rise in serum prostate-specific antigen (PSA) levels, the progression of pre-existing disease, and/or the appearance of new metastases.

  2 years

Secondary Outcomes (2)

• CRPC free survival

  4 years

• Overall patients' survival

  4 years

Study Arms (2)

Investigational arm

ACTIVE COMPARATOR

Metformin will be added to standard of care

Drug: Metformin

Control arm

NO INTERVENTION

Patients will treated according to Standard of care only

Interventions

Metformin DRUG

Metformin will be added as a daily treatment to the standard treatment in both neoadjuvant and adjuvant settings of locally advanced cases and lifelong to metastatic cases. The starting daily dose of metformin is 850mg Once daily, to be increased to 850 mg if tolerated

Also known as: Cidophage

Investigational arm

Eligibility Criteria

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

You may qualify if:

• High-risk newly diagnosed non-metastatic node-negative disease at least two of:
• Stage T3/4, PSA≥40ng/ml or Gleason sum score 8-10
• Intention to treat with radical radiotherapy (unless there is a contraindication)
• OR newly diagnosed metastatic or node-positive disease at least one of:
• Stage T any N+ M0
• Stage T any Nany M+
• OR previously treated with radical surgery and/or radiotherapy, now relapsing
• At least one of:
• (-PSA ≥4ng/ml and rising with doubling time less than 6 months,N+, M+)
• And for all patients
• Age \> 18 years
• Histologically confirmed prostate adenocarcinoma
• Intention to treat with long-term androgen deprivation therapy
• Fit for all protocol treatment and follow-up, ECOG performance status 0-2
• Diabetic and non-diabetic patients

You may not qualify if:

• Age \< 18 years
• Excessive alcohol intake, acute or chronic
• Patients already treated with Metformin or an analoge
• Known hypersensitivity or allergy to Metformin or any of the excipients.
• Patients with a history of lactic acidosis
• Patient treated for a cancer other than prostate cancer, with the exception of basal cell carcinoma
• Acute or chronic metabolic acidosis.
• Patients suffering from severe dehydration.
• Patients with chronic heart failure.
• Patients with hepatic impairment.
• Patients with severe renal disease.

Sponsors & Collaborators

• Mansoura University: lead

Study Sites (1)

Mansoura university

Al Mansurah, 35516, Egypt

RECRUITING

Related Publications (12)

• Colquhoun AJ, Venier NA, Vandersluis AD, Besla R, Sugar LM, Kiss A, Fleshner NE, Pollak M, Klotz LH, Venkateswaran V. Metformin enhances the antiproliferative and apoptotic effect of bicalutamide in prostate cancer. Prostate Cancer Prostatic Dis. 2012 Dec;15(4):346-52. doi: 10.1038/pcan.2012.16. Epub 2012 May 22.

  PMID: 22614062 RESULT

• Dowling RJ, Goodwin PJ, Stambolic V. Understanding the benefit of metformin use in cancer treatment. BMC Med. 2011 Apr 6;9:33. doi: 10.1186/1741-7015-9-33.

  PMID: 21470407 RESULT

• Eriksson A, Attvall S, Bonnier M, Eriksson JW, Rosander B, Karlsson FA. Short-term effects of metformin in type 2 diabetes. Diabetes Obes Metab. 2007 Jul;9(4):483-9. doi: 10.1111/j.1463-1326.2006.00624.x.

  PMID: 17587390 RESULT

• Hamilton RJ. Metformin for castrate-resistant prostate cancer: learning more about an old dog's new tricks. Eur Urol. 2014 Sep;66(3):475-7; discussion 477-8. doi: 10.1016/j.eururo.2014.01.013. Epub 2014 Jan 23. No abstract available.

  PMID: 24472709 RESULT

• Hankinson SJ, Fam M, Patel NN. A review for clinicians: Prostate cancer and the antineoplastic properties of metformin. Urol Oncol. 2017 Jan;35(1):21-29. doi: 10.1016/j.urolonc.2016.10.009. Epub 2016 Nov 9.

  PMID: 27836248 RESULT

• Mayer MJ, Klotz LH, Venkateswaran V. Metformin and prostate cancer stem cells: a novel therapeutic target. Prostate Cancer Prostatic Dis. 2015 Dec;18(4):303-9. doi: 10.1038/pcan.2015.35. Epub 2015 Jul 28.

  PMID: 26215782 RESULT

• Ranasinghe WK, Sengupta S, Williams S, Chang M, Shulkes A, Bolton DM, Baldwin G, Patel O. The effects of nonspecific HIF1alpha inhibitors on development of castrate resistance and metastases in prostate cancer. Cancer Med. 2014 Apr;3(2):245-51. doi: 10.1002/cam4.189. Epub 2014 Jan 27.

  PMID: 24464861 RESULT

• 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 RESULT

• Saylor PJ, Smith MR. Metabolic complications of androgen deprivation therapy for prostate cancer. J Urol. 2009 May;181(5):1998-2006; discussion 2007-8. doi: 10.1016/j.juro.2009.01.047. Epub 2009 Mar 14.

  PMID: 19286225 RESULT

• Song CW, Lee H, Dings RP, Williams B, Powers J, Santos TD, Choi BH, Park HJ. Metformin kills and radiosensitizes cancer cells and preferentially kills cancer stem cells. Sci Rep. 2012;2:362. doi: 10.1038/srep00362. Epub 2012 Apr 12.

  PMID: 22500211 RESULT

• Spratt DE, Zhang Z, Zelefsky MJ. Reply to Leah Bensimon, Samy Suissa, and Laurent Azoulay's letter to the editor re: Daniel E. Spratt, Chi Zhang, Zachary S. Zumsteg, Xin Pei, Zhigang Zhang, Michael J. Zelefsky. metformin and prostate cancer: reduced development of castration-resistant disease and prostate cancer mortality. Eur Urol 2013;63:709-16. Eur Urol. 2013 Aug;64(2):e29-30. doi: 10.1016/j.eururo.2013.04.015. Epub 2013 Apr 19. No abstract available.

  PMID: 23619389 RESULT

• Heidenreich A, Bastian PJ, Bellmunt J, Bolla M, Joniau S, van der Kwast T, Mason M, Matveev V, Wiegel T, Zattoni F, Mottet N; European Association of Urology. EAU guidelines on prostate cancer. Part II: Treatment of advanced, relapsing, and castration-resistant prostate cancer. Eur Urol. 2014 Feb;65(2):467-79. doi: 10.1016/j.eururo.2013.11.002. Epub 2013 Nov 12.

  PMID: 24321502 RESULT

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

• Reham Alghandour

  Mansoura University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Reham Alghandour

CONTACT

01002682875; Rehamalghandour@mans.edu.eg

Ahmed Elshaal

CONTACT

01001855490; Elshalam@hotmail.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant lecturer

Study Record Dates

• First Submitted: April 9, 2017
• First Posted: May 2, 2017
• Study Start: January 1, 2017
• Primary Completion: January 1, 2018
• Study Completion: January 1, 2020
• Last Updated: May 2, 2017

Record last verified: 2017-04

Data Sharing

• IPD Sharing: Will not share

Locations

EG (1)