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

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

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 Overview

• Status: Completed
• Conditions: Neoplasms; Prostatic Neoplasms
• Intervention / Treatment: Drug: mitoxantrone; Drug: prednisone; Drug: cabazitaxel (XRP6258) (RPR116258)

• Study Type: Interventional
• Enrollment (Actual): 755
• Phase: Phase 3

Contacts and Locations

Study Locations

• Argentina
  • Buenos Aires, Argentina
    • sanofi-aventis Argentina
• Belgium
  • Diegem, Belgium
    • sanofi-aventis Belgium
• Brazil
  • Sao Paulo, Brazil
    • sanofi-aventis Brazil
• Canada
  • Quebec
    • Laval, Quebec, Canada
      • sanofi-aventis Canada
• Chile
  • Santiago, Chile
    • sanofi-aventis Chile
• Czech Republic
  • Praha, Czech Republic
    • sanofi-aventis Czech Republic
• Denmark
  • Horsholm, Denmark
    • sanofi-aventis Denmark
• Finland
  • Helsinki, Finland
    • sanofi-aventis Finland
• France
  • Paris, France
    • Sanofi-Aventis France
• Germany
  • Berlin, Germany
    • Sanofi-aventis Germany
• Hungary
  • Budapest, Hungary
    • sanofi-aventis Hungaria
• India
  • Mumbai, India
    • sanofi-aventis India
• Italy
  • Milano, Italy
    • sanofi-aventis Italy
• Korea, Republic of
  • Seoul, Korea, Republic of
    • sanofi-aventis South Korea
• Mexico
  • Mexico, Mexico
    • Sanofi-Aventis Mexico
• Netherlands
  • Gouda, Netherlands
    • sanofi-aventis Netherlands
• Russian Federation
  • Moscow, Russian Federation
    • sanofi-aventis Russia
• Singapore
  • Singapore, Singapore
    • sanofi-aventis Singapore
• Slovakia
  • Bratislava, Slovakia
    • sanofi-aventis Slovakia
• South Africa
  • Midrand, South Africa
    • sanofi-aventis South Africa
• Spain
  • Barcelona, Spain
    • sanofi-aventis Spain
• Sweden
  • Bromma, Sweden
    • sanofi-aventis Sweden
• Taiwan
  • Taipei, Taiwan
    • sanofi-aventis Taiwan
• Turkey
  • Istanbul, Turkey
    • Sanofi-aventis Turkey
• United Kingdom
  • Surrey
    • Guildford, Surrey, United Kingdom
      • Sanofi-Aventis UK
• United States
  • New Jersey
    • Bridgewater, New Jersey, United States, 08807
      • Sanofi-Aventis US

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: 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	Drug: prednisone; 10 mg daily administered by oral route; 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 Names: Jevtana

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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)
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)
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)
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)
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)
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)
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)

Collaborators and Investigators

• Sponsor: Sanofi

Publications and helpful links

General Publications

• Lorente D, Mateo J, Templeton AJ, Zafeiriou Z, Bianchini D, Ferraldeschi R, Bahl A, Shen L, Su Z, Sartor O, de Bono JS. Baseline neutrophil-lymphocyte ratio (NLR) is associated with survival and response to treatment with second-line chemotherapy for advanced prostate cancer independent of baseline steroid use. Ann Oncol. 2015 Apr;26(4):750-755. doi: 10.1093/annonc/mdu587. Epub 2014 Dec 23.
• Bahl A, Oudard S, Tombal B, Ozguroglu M, Hansen S, Kocak I, Gravis G, Devin J, Shen L, de Bono JS, Sartor AO; TROPIC Investigators. Impact of cabazitaxel on 2-year survival and palliation of tumour-related pain in men with metastatic castration-resistant prostate cancer treated in the TROPIC trial. Ann Oncol. 2013 Sep;24(9):2402-8. doi: 10.1093/annonc/mdt194. Epub 2013 May 30.
• Pouessel D, Oudard S, Gravis G, Priou F, Shen L, Culine S. [Cabazitaxel for metastatic castration-resistant prostate cancer progressing after docetaxel treatment: the TROPIC study in France]. Bull Cancer. 2012 Jul-Aug;99(7-8):731-41. doi: 10.1684/bdc.2012.1608. French.
• 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. doi: 10.1016/S0140-6736(10)61389-X.

Study record dates

Study Major Dates

• Study Start: January 1, 2007
• Primary Completion (Actual): September 1, 2009
• Study Completion (Actual): September 1, 2009

Study Registration Dates

• First Submitted: December 28, 2006
• First Submitted That Met QC Criteria: December 28, 2006
• First Posted (Estimate): December 29, 2006

Study Record Updates

• Last Update Posted (Estimate): March 10, 2011
• Last Update Submitted That Met QC Criteria: March 4, 2011
• Last Verified: March 1, 2011

More Information

Terms related to this study

• Keywords: Cancer; Prostate
• Additional Relevant MeSH Terms: Urogenital Neoplasms; Neoplasms by Site; Genital Neoplasms, Male; Prostatic Diseases; Neoplasms; Prostatic Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Enzyme Inhibitors; Analgesics; Sensory System Agents; Anti-Inflammatory Agents; Antineoplastic Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Prednisone; Mitoxantrone
• Other Study ID Numbers: EFC6193

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No