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

Neoplasms Clinical Trial

— TROPIC  

Official title:

A Randomized, Open Label Multi-Center Study of XRP6258 at 25 mg/m^2 in Combination With Prednisone Every 3 Weeks Compared to Mitoxantrone in Combination With Prednisone For The Treatment of Hormone Refractory Metastatic Prostate Cancer Previously Treated With A Taxotere®-Containing Regimen

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00417079
• Other study ID #: EFC6193
• Status: Completed
• Phase: Phase 3
• First received: December 28, 2006
• Last updated: March 4, 2011
• Start date: January 2007
• Est. completion date: September 2009

Study information

• Verified date: March 2011
• Source: Sanofi
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationUnited Kingdom: Medicines and Healthcare Products Regulatory AgencyCanada: Health Canada
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 755
• Est. completion date: September 2009
• Est. primary completion date: September 2009
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 18 Years and older

Eligibility

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.

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Neoplasms
• Prostatic Neoplasms

Intervention

Drug:
• cabazitaxel (XRP6258) (RPR116258)
25 mg/m^2 administered by intravenous (IV) route over 1 hour on day 1 of each 21-day cycle
• mitoxantrone
12 mg/m^2 administered by intravenous (IV) route over 15-30 minutes on day 1 of each 21-day cycle
• prednisone
10 mg daily administered by oral route

Locations

Country	Name	City	State
Argentina	sanofi-aventis Argentina	Buenos Aires
Belgium	sanofi-aventis Belgium	Diegem
Brazil	sanofi-aventis Brazil	Sao Paulo
Canada	sanofi-aventis Canada	Laval	Quebec
Chile	sanofi-aventis Chile	Santiago
Czech Republic	sanofi-aventis Czech Republic	Praha
Denmark	sanofi-aventis Denmark	Horsholm
Finland	sanofi-aventis Finland	Helsinki
France	sanofi-aventis France	Paris
Germany	sanofi-aventis Germany	Berlin
Hungary	Sanofi-Aventis Hungaria	Budapest
India	sanofi-aventis India	Mumbai
Italy	sanofi-aventis Italy	Milano
Korea, Republic of	sanofi-aventis South Korea	Seoul
Mexico	sanofi-aventis Mexico	Mexico
Netherlands	sanofi-aventis Netherlands	Gouda
Russian Federation	sanofi-aventis Russia	Moscow
Singapore	sanofi-aventis Singapore	Singapore
Slovakia	sanofi-aventis Slovakia	Bratislava
South Africa	sanofi-aventis South Africa	Midrand
Spain	sanofi-aventis Spain	Barcelona
Sweden	sanofi-aventis Sweden	Bromma
Taiwan	sanofi-aventis Taiwan	Taipei
Turkey	sanofi-aventis Turkey	Istanbul
United Kingdom	sanofi-aventis UK	Guildford	Surrey
United States	sanofi-aventis US	Bridgewater	New Jersey

Sponsors (1)

Lead Sponsor	Collaborator
Sanofi

Countries where clinical trial is conducted

United States,  Argentina,  Belgium,  Brazil,  Canada,  Chile,  Czech Republic,  Denmark,  Finland,  France,  Germany,  Hungary,  India,  Italy,  Korea, Republic of,  Mexico,  Netherlands,  Russian Federation,  Singapore,  Slovakia,  South Africa,  Spain,  Sweden,  Taiwan,  Turkey,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	From the date of randomization up to 104 weeks (study cut-off)	No
Secondary	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	From the date of randomization up to 104 weeks (study cut-off)	No
Secondary	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.	From the date of randomization up to 104 weeks (study cut-off)	No
Secondary	Time to Tumor Progression	Time to tumor progression is defined as the number of months from randomization until evidence of progressive disease (RECIST)	From the date of randomization up to 104 weeks (study cut-off)	No
Secondary	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.	at screening, day 1 of every treatment cycle, up to 104 weeks (study cut-off)	No
Secondary	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.	from baseline up to 104 weeks (study cut-off)	No
Secondary	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)	from baseline up to 104 weeks (study cut-off)	No
Secondary	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.	from baseline up to 104 weeks (study cut-off)	No