Metformin-Docetaxel Association in Metastatic Hormone-refractory Prostate Cancer (TAXOMET)
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|ClinicalTrials.gov Identifier: NCT01796028|
Recruitment Status : Completed
First Posted : February 21, 2013
Last Update Posted : June 6, 2018
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|
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||100 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)|
|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|
|Actual Primary Completion Date :||December 2015|
|Actual Study Completion Date :||May 31, 2018|
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
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
Other Name: GLUCOPHAGE
- PSA response rate [ Time Frame: Time until main objective analysis is 5 years ]
- Biochemical and clinical progression-free survival [ Time Frame: 5 years ]
- Overall survival: Overall survival will be calculated from the date of randomization to the date of death from any causes. [ Time Frame: 5 years ]
- Tolerance of the association: Tolerance will be assessed according to the NCI-CTCAE scale, version 4.0. [ Time Frame: 5 YEARS ]
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
|Centre ANTOINE LACASSAGNE|
|Nice, France, 06189|
|Principal Investigator:||Jean-Marc FERRERO, PhD||Centre Antoine Lacassagne|