XRP6258 Plus Prednisone Compared to Mitoxantrone Plus Prednisone in Hormone Refractory Metastatic Prostate Cancer - Full Text View

Sponsor:	Sanofi-Aventis
Information provided by:	Sanofi-Aventis
ClinicalTrials.gov Identifier:	NCT00417079

Purpose

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.

Condition	Intervention	Phase
Neoplasms Prostatic Neoplasms	Drug: cabazitaxel (XRP6258) (RPR116258) Drug: mitoxantrone Drug: prednisone	Phase III

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

Resource links provided by NLM:

MedlinePlus related topics: Cancer Prostate Cancer

Drug Information available for: Prednisone Mitoxantrone Mitoxantrone hydrochloride

U.S. FDA Resources

Further study details as provided by Sanofi-Aventis:

Primary Outcome Measures:

Overall Survival [ Time Frame: From the date of randomization up to 104 weeks (study cut-off) ] [ Designated as safety issue: No ]
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.

Secondary Outcome Measures:

Time to Progression Free Survival (PFS) [ Time Frame: From the date of randomization up to 104 weeks (study cut-off) ] [ Designated as safety issue: No ]
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
Overall Tumor Response [ Time Frame: From the date of randomization up to 104 weeks (study cut-off) ] [ Designated as safety issue: No ]
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 to Tumor Progression [ Time Frame: From the date of randomization up to 104 weeks (study cut-off) ] [ Designated as safety issue: No ]
Time to tumor progression is defined as the number of months from randomization until evidence of progressive disease (RECIST)
Time to Prostatic Specific Antigen (PSA) Progression [ Time Frame: at screening, day 1 of every treatment cycle, up to 104 weeks (study cut-off) ] [ Designated as safety issue: No ]
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.
PSA (Prostate-Specific Antigen) Response [ Time Frame: from baseline up to 104 weeks (study cut-off) ] [ Designated as safety issue: No ]
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 to Pain Progression [ Time Frame: from baseline up to 104 weeks (study cut-off) ] [ Designated as safety issue: No ]
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)
Pain Response [ Time Frame: from baseline up to 104 weeks (study cut-off) ] [ Designated as safety issue: No ]
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.

Enrollment:	755
Study Start Date:	January 2007
Study Completion Date:	September 2009
Primary Completion Date:	September 2009 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Active Comparator: Mitoxantrone + Prednisone Mitoxantrone + Prednisone	Drug: mitoxantrone 12 mg/m^2 administered by intravenous (IV) route over 15-30 minutes on day 1 of each 21-day cycle Drug: prednisone 10 mg daily administered by oral route
Experimental: Cabazitaxel + Prednisone Cabazitaxel + Prednisone	Drug: cabazitaxel (XRP6258) (RPR116258) 25 mg/m^2 administered by intravenous (IV) route over 1 hour on day 1 of each 21-day cycle Other Name: Jevtana Drug: prednisone 10 mg daily administered by oral route

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Male
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria

Histologically or cytologically confirmed adenocarcinoma of the prostate that is refractory to hormone therapy and previously treated with a Taxotere®-containing regimen.
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.
Surgical or hormone-induced castration
Life expectancy > 2 months
Eastern Cooperative Oncology Group (ECOG) performance status 0 - 2

Exclusion criteria

Previous treatment with mitoxantrone
Previous treatment with <225 mg/m^2 cumulative dose of Taxotere (or docetaxel)
Prior radiotherapy to ≥ 40% of bone marrow
Surgery, radiation, chemotherapy, or other anti-cancer therapy within 4 weeks prior to enrollment in the study
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
Known brain or leptomeningeal involvement
Other concurrent serious illness or medical conditions
Inadequate organ function evidenced by unacceptable laboratory results

The investigator will evaluate whether there are other reasons why a patient may not participate.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00417079

Show 26 Study Locations

Sponsors and Collaborators

Sanofi-Aventis

Investigators

Study Director:

ICD

Sanofi-Aventis

More Information

No publications provided by Sanofi-Aventis

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

de Bono JS, Oudard S, Ozguroglu M, Hansen S, Machiels JP, Kocak I, Gravis G, Bodrogi I, Mackenzie MJ, Shen L, Roessner M, Gupta S, Sartor AO; TROPIC Investigators. Prednisone plus cabazitaxel or mitoxantrone for metastatic castration-resistant prostate cancer progressing after docetaxel treatment: a randomised open-label trial. Lancet. 2010 Oct 2;376(9747):1147-54.

Responsible Party:	International Clinical Development Study Director, sanofi-aventis
ClinicalTrials.gov Identifier:	NCT00417079 History of Changes
Other Study ID Numbers:	EFC6193
Study First Received:	December 28, 2006
Results First Received:	September 20, 2010
Last Updated:	March 4, 2011
Health Authority:	United States: Food and Drug Administration; United Kingdom: Medicines and Healthcare Products Regulatory Agency; Canada: Health Canada

Keywords provided by Sanofi-Aventis:

Cancer
Prostate

Additional relevant MeSH terms:

Neoplasms
Prostatic Neoplasms
Genital Neoplasms, Male
Urogenital Neoplasms
Neoplasms by Site
Genital Diseases, Male
Prostatic Diseases
Mitoxantrone
Prednisone
Antineoplastic Agents
Therapeutic Uses

Pharmacologic Actions
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Central Nervous System Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Antineoplastic Agents, Hormonal
Anti-Inflammatory Agents

ClinicalTrials.gov processed this record on February 12, 2012