GEMOX in Docetaxel-Refractory Castration-Resistant Prostate Cancer

Study Overview
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Brief Summary
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Prostate cancer is one of the most common malignancies affecting men all over the World. Metastatic prostate cancer responds to androgen deprivation for a variable period (20-25 months). Prostate cancer that grows despite castrate levels of testosterone and that no longer responds to any form of hormonal manipulation is defined as castrate resistant prostate cancer (CRPC). Docetaxel combined with prednisolone has been shown to not only improve QOL and PSA response in CRPC, but also extend the overall survival1. However, the efficacy of the drug has not been universally effective, and nearly all patients have disease progression after docetaxel treatment. After failure of a docetaxel regimen, With the exception of cabazitaxel or abiraterone, which are not widely and easily availabe in Korea, little treatment regimen can be applied to the patients with reasonable response and benefits. Gemcitabine is a nucleoside analog with activity against a broad spectrum of solid tumors. When gemcitabine is used as first-line therapy for CRPC, disease control rate was 33% with median duration of 7.1 months. When it is combined with prednisone and zoledronic acid in pretreated patients with CRPC, the PSA response rate was 23% with a disease control rate of 57% in patients with measurable disease. Oxaliplatin is newer platinum agent that has favorable toxicity profile and evidence of activity in cisplatin-resistant cell lines. Droz et al. performed a multicenter phase II study in 54 patients with metastatic CRPC who were randomized to receive oxaliplatin either alone or with 5-FU. More than 50% of the patients had received prior chemotherapy including cisplatin. Despite heavy pretreatment, PSA desclines were noted in 11% and 19% of patients in each arm. Gemcitabine plus oxaliplatin combination was widely studied and has been reported to be safe and effective in various cancers. This study is to assess the efficacy and safety of GEMOX in docetaxel-refractory CRPC.

Official Title
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A Prosepctive Phase II Study of Gemcitabine and Oxaliplatin in Combination With Prednisolone for the Treatment of Hormone Refracotry Metastatic Prostate Cancer Previously Treated With Docetaxel Regimen

Conditions
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Prostate Cancer

Intervention / Treatment
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* Drug: GEMOX


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically or cytologically confirmed adenocarcinoma of the prostate Clinical or radiologic evidence of metastatic disease Documented disease progression during hormone therapy (ADT plus antiandrogen) and no response to ADT withdrawal Docetaxel-refractory disease defined as disease progression documented either during treatment of within 60 days after the cessation of treatment with docetaxel Prior exposure to estramustine or mitoxantrone is allowed KPS ≥ 60 No prior radioisotope therapy No prior radiotherapy 25% or more of the bone marrow No peripheral neuropathy grade 2 or worse Adequate organ and bone marrow function Exclusion Criteria: Other tumor type than adenocarcinoma Presence or history of CNS metastasis Other serious illness or medical conditions

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: GEMOX<br>GEMOX treatment | Drug: GEMOX<br>* Gemcitabine 1000 mg/m2 IV on day 1 every 2 weeks (fixed-dose rate 10 mg/m2/min) Oxaliplatin 100 mg/m2 IV on day 1 every 2 weeks Prednisolone 5 mg twice a day orally daily<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| PSA response | Based on PCWG 1.0 | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| PSA decline | Based on PCWG 2.0 | 6 months | 
| Time to PSA progression |  | 12 months | 
| Composite progression-free survival | Based on RECIST, bone scan, and performance status | 12 months | 
| RECIST Response | Based on RECIST v 1.1 | 6 months | 
| Safety | Based on NCI CTCAE v. 4.03 | 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Castration-resistant prostate cancer, Docetaxel-refractory status