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Metformin-Docetaxel Association in Metastatic Hormone-refractory Prostate Cancer (TAXOMET)

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ClinicalTrials.gov Identifier: NCT01796028
Recruitment Status : Active, not recruiting
First Posted : February 21, 2013
Last Update Posted : December 1, 2017
Sponsor:
Information provided by (Responsible Party):

Study Description
Brief Summary:

Prostate cancer is the second leading cause of mortality in men, representing 10 deaths about of 100 cancers (INVS 2009). Treatment for metastatic prostate cancer, when becoming resistant to hormone-treatment, is mostly resumed to a relatively ineffective chemotherapy (Docetaxel/TAXOTERE®) (1). Recently, numerous clinical and preclinical works showed that Metformin could represent an excellent candidate for treatment of advanced prostate cancer. This is a widely prescribed drug, for type 2 diabetes, with clinical advantage of exhibiting very rare serious side effects. On the other hand, the use of this molecule in patients was associated with a decrease of tumors incidence, in particular prostate cancer (2). Numerous in vitro and in vivo studies support its role as an anti-cancer drug, in several cell lines (3). These experimental results are consistent with a clinical trial pilot study, performed in colorectal cancer, showing anti proliferative effect of Metformin (4). In the field of prostate, F. Bost in J.F. Tanti's team (INSERM U895, Nice) demonstrated that Metformin inhibits cell viability of human prostate cancer cells, via mTOR downregulation and decrease tumor growth in a xenograft model (5). Furthermore, preclinical data performed by this team showed that Metformin increased significantly apoptosis induced by TAXOTERE®. Therefore, by targeting specifically cancer cell metabolism, Metformin offers new promising therapeutic strategy.

The primary objective of this randomized study is to evaluate the biological efficacy of Metformin combination with TAXOTERE® in patients with metastatic hormone-refractory prostate cancer. To achieve this purpose, PSA response rate will be evaluated according to ASTRO definitions (Bubley, Carducci et al. 1999). Concurrently, secondary endpoints will be under investigation in order to evaluate the clinical response according to RECIST criteria, the overall and free-progression survival and the quality of life. Toxicity assessment will also be performed regarding to this drug combination.

Considering the well tolerability of Metformin and the first clinical and pre-clinical data reports of it use in cancer treatment, combining Docetaxel (TAXOTERE®) with Metformin may represent a promising strategy for treatment of hormone-refractory prostate cancer.


Condition or disease Intervention/treatment Phase
Prostatic Neoplasms Drug: METFORMIN Drug: Placebo Drug: TAXOTERE® Phase 2

  Show Detailed Description

Study Design

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 100 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Multicentric, Randomized, Phase II Study Evaluating the Combination of METFORMIN With TAXOTERE®+Metformine Placebo Versus TAXOTERE®+Metformin for the Treatment of Metastatic Hormone-refractory Prostate Cancer.
Study Start Date : January 2013
Primary Completion Date : December 2015
Estimated Study Completion Date : December 2017

Resource links provided by the National Library of Medicine

U.S. FDA Resources

Arms and Interventions

Arm Intervention/treatment
Placebo Comparator: Arm A : TAXOTERE® + Metformin placebo
Docetaxel (TAXOTERE®) will be administered at 75 mg/m2. Metformin (or placebo) is formulated into 850 mg tablets for oral administration and is to be dispensed twice a day on a continuous daily dosing schedule
Drug: Placebo Drug: TAXOTERE®
Experimental: Arm B : TAXOTERE® + Metformin
Docetaxel (TAXOTERE®) will be administered at 75 mg/m2. Metformin is formulated into 850 mg tablets for oral administration and is to be dispensed twice a day on a continuous daily dosing schedule
Drug: METFORMIN
Other Name: GLUCOPHAGE
Drug: TAXOTERE®


Outcome Measures

Primary Outcome Measures :
  1. PSA response rate [ Time Frame: Time until main objective analysis is 5 years ]

Secondary Outcome Measures :
  1. Biochemical and clinical progression-free survival [ Time Frame: 5 years ]

Other Outcome Measures:
  1. Overall survival: Overall survival will be calculated from the date of randomization to the date of death from any causes. [ Time Frame: 5 years ]
  2. Tolerance of the association: Tolerance will be assessed according to the NCI-CTCAE scale, version 4.0. [ Time Frame: 5 YEARS ]

Eligibility Criteria

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

Inclusion Criteria:

  • - Age > 18 years
  • Histologically confirmed prostate adenocarcinoma.
  • Karnofsky Performance Score > 50%
  • Evidence of metastatic disease by the presence of documented locoregional or distant metastases on CT scan of the abdomen and/or pelvis, or bone scintigraphy
  • Hormone Resistance Prostate Cancer defined as an increase in PSA level (3 consecutive measurements) after hormonal treatment (surgical castration or androgen blockade)
  • No prior chemotherapy (excepted phosphate estramustine or Estracyt®)
  • At least one month had to have elapsed between the withdrawal of antiandrogens and enrolment, except LH-RH agonist therapy that must be continued throughout this study.
  • Hormonal castration confirmed biologically (testosterone < 0.5 ng/ml)
  • Patient with adequate organ function:

    • Absolute neutrophil count (ANC) ≥ 1.5 x 109/L
    • Haemoglobin ≥ 9 g/dL
    • Platelets (PTL) ≥ 100 x 109/L
    • AST - ALAT ≤ 2.5x ULN
    • Bilirubin ≤ 1.5 x ULN
    • Creatinine < 150 µmol/l
    • Alkaline phosphatases ≤ 2,5 x ULN
  • Patient with life expectancy > 3 months
  • Information delivered to patient and informed consent signed by the patient or legal representative
  • Patient affiliated with a health insurance system

Exclusion Criteria:

  • The patient with at least one of the following criteria could not be included:
  • Age < 18 years
  • Patient with type II or type I diabetes
  • Excessive alcohol intake, acute or chronic.
  • Patients already treated with Metformin or an analog
  • Known hypersensitivity or allergy to Metformin HCl or any of the excipients.
  • Patients with a history of lactic acidosis
  • PSA increasement without lesions confirmed by radiography and/or bone scan.
  • Testosteronemia > 0.5 ng/ml
  • Any radiation within 4 weeks prior to study entry
  • Strontium 89 administration within 3 month before inclusion
  • Patient with active central nervous system (CNS) metastasis or with history of CNS metastasis
  • Peripheral neuropathy with grade > 3 (NCI), unrelated to cancer.
  • Patient treated for a cancer other than prostate cancer, with the exception of basal cell carcinoma
  • Treatment with any investigational agent
  • Treatment on another therapeutic clinical trial within 30 days before enrolment
  • Acute or chronic metabolic acidosis
  • Patients suffering from severe dehydration
  • Permanent contraindication to corticosteroids
  • Patient with history of poor compliance or current or past psychiatric conditions or severe acute or chronic medical conditions that would interfere with the ability to comply with the study protocol, such as completion of QoL questionnaire.
  • Patient enable to give informed consent
Contacts and Locations

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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): NCT01796028


Locations
France
Centre ANTOINE LACASSAGNE
Nice, France, 06189
Sponsors and Collaborators
Centre Antoine Lacassagne
Investigators
Principal Investigator: Jean-Marc FERRERO, PhD Centre Antoine Lacassagne
More Information

Additional Information:
Responsible Party: Centre Antoine Lacassagne
ClinicalTrials.gov Identifier: NCT01796028     History of Changes
Other Study ID Numbers: 2012-000530-19
2010/35 ( Registry Identifier: TAXOMET )
First Posted: February 21, 2013    Key Record Dates
Last Update Posted: December 1, 2017
Last Verified: November 2017

Keywords provided by Centre Antoine Lacassagne:
Prostate Cancer

Additional relevant MeSH terms:
Prostatic Neoplasms
Genital Neoplasms, Male
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
Genital Diseases, Male
Prostatic Diseases
Metformin
Docetaxel
Hormones
Hypoglycemic Agents
Physiological Effects of Drugs
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Hormones, Hormone Substitutes, and Hormone Antagonists