XRP6258 Plus Prednisone Compared to Mitoxantrone Plus Prednisone in Hormone Refractory Metastatic Prostate Cancer

Sanofi755 enrolled

Overview

This is a randomized, open-label, multi-center study comparing the safety and efficacy of XRP6258 plus prednisone to mitoxantrone plus prednisone in the treatment of hormone refractory metastatic prostate cancer previously treated with a Taxotere®-containing regimen. The primary objective is overall survival. Secondary objectives include progression free survival, overall response rate, prostate-specific antigen (PSA) response/progression, pain response/progression, overall safety, and pharmacokinetics. Patients will be treated until disease progression, death, unacceptable toxicity, or for a maximum of 10 cycles. Patients will have long-term follow-up for a maximum of up to 2 years.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

755

Conditions

Neoplasms Prostatic Neoplasms

Interventions

Eligibility

Sex: MALEMin age: 18 Years

Medical Language ↔ Plain English

Inclusion Criteria 1. Histologically or cytologically confirmed adenocarcinoma of the prostate that is refractory to hormone therapy and previously treated with a Taxotere®-containing regimen. 2. Documented progression of disease (demonstrating at least one visceral or soft tissue metastatic lesion, including a new lesion). Patients with non-measurable disease must have documented rising prostate-specific antigen (PSA) levels or appearance of new lesion. 3. Surgical or hormone-induced castration 4. Life expectancy \> 2 months 5. Eastern Cooperative Oncology Group (ECOG) performance status 0 - 2 Exclusion criteria 1. Previous treatment with mitoxantrone 2. Previous treatment with \<225 mg/m\^2 cumulative dose of Taxotere (or docetaxel) 3. Prior radiotherapy to ≥ 40% of bone marrow 4. Surgery, radiation, chemotherapy, or other anti-cancer therapy within 4 weeks prior to enrollment in the study 5. Other prior malignancy, except for adequately treated superficial basal cell skin cancer, or any other cancer from which the patient has been disease-free for less than 5 years 6. Known brain or leptomeningeal involvement 7. Other concurrent serious illness or medical conditions 8. Inadequate organ function evidenced by unacceptable laboratory results The investigator will evaluate whether there are other reasons why a patient may not participate.

Locations (26)

sanofi-aventis US

Bridgewater, New Jersey, United States

sanofi-aventis Argentina

Buenos Aires, Argentina

sanofi-aventis Belgium

Diegem, Belgium

sanofi-aventis Brazil

São Paulo, Brazil

sanofi-aventis Canada

Laval, Quebec, Canada

sanofi-aventis Chile

Santiago, Chile

sanofi-aventis Czech Republic

Prague, Czechia

sanofi-aventis Denmark

Hørsholm, Denmark

sanofi-aventis Finland

Helsinki, Finland

sanofi-aventis France

Paris, France

...and 16 more locations

Outcomes

Primary Outcomes

Overall Survival

Overall survival was defined as the time interval from the date of randomization to the date of death due to any cause. In the absence of confirmation of death, the survival time was censored at the last date patient was known to be alive or at the cut-off date, whichever had come first.

Time frame: From the date of randomization up to 104 weeks (study cut-off)

Secondary Outcomes

Time to Progression Free Survival (PFS)

Progression free survival was defined as a composite endpoint evaluated from the date of randomization to the date of tumor progression, PSA progression, pain progression, or death due to any cause, whichever occurred first

Time frame: From the date of randomization up to 104 weeks (study cut-off)

Overall Tumor Response

Tumor Overall Response Rate (ORR) (only in patients with measurable disease): Objective responses (Complete Response and Partial Response) for measurable disease as assessed by investigators according to RECIST criteria. Complete Response (CR) is defined as: Disappearance of all target lesions. Partial Response (PR) is defined as: At least a 30% decrease in the sum of longest diameter (LD) of target lesions taking as reference baseline sum LD. Confirmation of objective responses will be performed by repeat tumor imaging (CT scans, MRI, bone scans) after the first documentation of response.

Time frame: From the date of randomization up to 104 weeks (study cut-off)

Time to Tumor Progression

Time to tumor progression is defined as the number of months from randomization until evidence of progressive disease (RECIST)

Time frame: From the date of randomization up to 104 weeks (study cut-off)

Time to Prostatic Specific Antigen (PSA) Progression

In PSA non-responders, progression will be defined as a 25% increase over nadir and increase in the absolute value PSA level by at least 5 ng/ml and confirmed by a second value at least 4 weeks later. In PSA responders and in patients not evaluable for PSA response at baseline, progression will be defined as a ≥50% increase over nadir, provided that the increase is a minimum of 5 ng/ml and confirmed by a second value at least 1 week later.

Time frame: at screening, day 1 of every treatment cycle, up to 104 weeks (study cut-off)

PSA (Prostate-Specific Antigen) Response

PSA response was defined as a ≥ 50% reduction in serum PSA, determined only for patients with a serum PSA ≥ 20ng/mL at baseline, confirmed by a repeat PSA ≥ 3 weeks later.

Time frame: from baseline up to 104 weeks (study cut-off)

Time to Pain Progression

Pain Progression is defined as an increase of ≥1 point in the median Personal Pain Intensity (PPI) from its nadir noted on 2 consecutive 3-week-apart visits or ≥25 % increase in the mean analgesic score compared with the baseline score \& noted on 2 consecutive 3-week-apart visits or requirement for local palliative radiotherapy. Evaluation of the PPI \& analgesic scores are based on the short-form McGill Pain Questionnaire which consists of 15 descriptors (11 sensory; 4 affective) which are rated on an intensity scale as 0=none (best) 1=mild 2=moderate 3=severe (worst) (TOTAL: 0=best 45=worst)

Time frame: from baseline up to 104 weeks (study cut-off)

Pain Response

Pain Response was defined as a two-point or greater reduction from baseline median Present Pain Intensity (PPI) score without an increased Analgesic Score (AS) or a decrease of ≥50% in the AS without an increase in the PPI score, maintained for at least 3 weeks.

Time frame: from baseline up to 104 weeks (study cut-off)