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

• ClinicalTrials.gov Identifier: NCT00417079
• Recruitment Status: Completed
• First Posted: December 29, 2006
• Results First Posted: December 23, 2010
• Last Update Posted: March 10, 2011
• Sponsor: Sanofi
• Information provided by: Sanofi

Tracking Information

• First Submitted Date: December 28, 2006
• First Posted Date: December 29, 2006
• Results First Submitted Date: September 20, 2010
• Results First Posted Date: December 23, 2010
• Last Update Posted Date: March 10, 2011
• Study Start Date: January 2007
• Actual Primary Completion Date: September 2009 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: December 22, 2010)

Overall Survival [ Time Frame: From the date of randomization up to 104 weeks (study cut-off) ]

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.

• Original Primary Outcome Measures (submitted: December 28, 2006): The primary outcome measure is overall survival defined as the time interval from the date of randomization to the date of death due to any cause.

Current Secondary Outcome Measures (submitted: December 22, 2010)

• Time to Progression Free Survival (PFS) [ Time Frame: From the date of randomization up to 104 weeks (study cut-off) ]
  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) ]
  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) ]
  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) ]
  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) ]
  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) ]
  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) ]
  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.

Original Secondary Outcome Measures (submitted: December 28, 2006)

• to be evaluated at screening, day 1 of every treatment cycle, end of study treatment, and in follow-up until documented progression: PSA levels
• Anti-tumor activity via Computerized Tomography / Magnetic Resonance Imaging (and bone scans, as indicated)
• Pain via an analgesic consumption score and the Present Pain Index over a one-week period
• Adverse events; laboratory abnormalities; vital signs

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: XRP6258 Plus Prednisone Compared to Mitoxantrone Plus Prednisone in Hormone Refractory Metastatic Prostate Cancer
• 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
• Brief 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.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

• 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
  Other Name: Jevtana
• 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

Study Arms

• Active Comparator: Mitoxantrone + Prednisone
  Mitoxantrone + Prednisone
  Interventions:

  • Drug: mitoxantrone
  • Drug: prednisone
• Experimental: Cabazitaxel + Prednisone
  Cabazitaxel + Prednisone
  Interventions:

  • Drug: cabazitaxel (XRP6258) (RPR116258)
  • Drug: prednisone

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.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: April 30, 2010): 755
• Original Enrollment (submitted: December 28, 2006): 720
• Actual Study Completion Date: September 2009
• Actual Primary Completion Date: September 2009 (Final data collection date for primary outcome measure)

Eligibility Criteria

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.

Sex/Gender

• Sexes Eligible for Study: Male

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: 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, United States
• Removed Location Countries: Poland, Uruguay

Administrative Information

• NCT Number: NCT00417079
• Other Study ID Numbers: EFC6193
• Has Data Monitoring Committee: Not Provided
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: International Clinical Development Study Director, sanofi-aventis
• Original Responsible Party: Not Provided
• Current Study Sponsor: Sanofi
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: ICD; Sanofi

• PRS Account: Sanofi
• Verification Date: March 2011