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

Primary Purpose

Neoplasms, Prostatic Neoplasms

Status
Completed
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
cabazitaxel (XRP6258) (RPR116258)
mitoxantrone
prednisone
Sponsored by
Sanofi
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Neoplasms focused on measuring Cancer, Prostate

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)MaleDoes not accept healthy volunteers

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.

Sites / Locations

  • sanofi-aventis US
  • sanofi-aventis Argentina
  • sanofi-aventis Belgium
  • sanofi-aventis Brazil
  • sanofi-aventis Canada
  • sanofi-aventis Chile
  • sanofi-aventis Czech Republic
  • sanofi-aventis Denmark
  • sanofi-aventis Finland
  • sanofi-aventis France
  • sanofi-aventis Germany
  • Sanofi-Aventis Hungaria
  • sanofi-aventis India
  • sanofi-aventis Italy
  • sanofi-aventis South Korea
  • sanofi-aventis Mexico
  • sanofi-aventis Netherlands
  • sanofi-aventis Russia
  • sanofi-aventis Singapore
  • sanofi-aventis Slovakia
  • sanofi-aventis South Africa
  • sanofi-aventis Spain
  • sanofi-aventis Sweden
  • sanofi-aventis Taiwan
  • sanofi-aventis Turkey
  • sanofi-aventis UK

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Experimental

Arm Label

Mitoxantrone + Prednisone

Cabazitaxel + Prednisone

Arm Description

Mitoxantrone + Prednisone

Cabazitaxel + Prednisone

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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
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 to Tumor Progression
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
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
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
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
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.

Full Information

First Posted
December 28, 2006
Last Updated
March 4, 2011
Sponsor
Sanofi
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1. Study Identification

Unique Protocol Identification Number
NCT00417079
Brief Title
XRP6258 Plus Prednisone Compared to Mitoxantrone Plus Prednisone in Hormone Refractory Metastatic Prostate Cancer
Acronym
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
Study Type
Interventional

2. Study Status

Record Verification Date
March 2011
Overall Recruitment Status
Completed
Study Start Date
January 2007 (undefined)
Primary Completion Date
September 2009 (Actual)
Study Completion Date
September 2009 (Actual)

3. Sponsor/Collaborators

Name of the Sponsor
Sanofi

4. Oversight

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Neoplasms, Prostatic Neoplasms
Keywords
Cancer, Prostate

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
755 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Mitoxantrone + Prednisone
Arm Type
Active Comparator
Arm Description
Mitoxantrone + Prednisone
Arm Title
Cabazitaxel + Prednisone
Arm Type
Experimental
Arm Description
Cabazitaxel + Prednisone
Intervention Type
Drug
Intervention Name(s)
cabazitaxel (XRP6258) (RPR116258)
Other Intervention Name(s)
Jevtana
Intervention Description
25 mg/m^2 administered by intravenous (IV) route over 1 hour on day 1 of each 21-day cycle
Intervention Type
Drug
Intervention Name(s)
mitoxantrone
Intervention Description
12 mg/m^2 administered by intravenous (IV) route over 15-30 minutes on day 1 of each 21-day cycle
Intervention Type
Drug
Intervention Name(s)
prednisone
Intervention Description
10 mg daily administered by oral route
Primary Outcome Measure Information:
Title
Overall Survival
Description
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 Outcome Measure Information:
Title
Time to Progression Free Survival (PFS)
Description
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)
Title
Overall Tumor Response
Description
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)
Title
Time to Tumor Progression
Description
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)
Title
Time to Prostatic Specific Antigen (PSA) Progression
Description
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)
Title
PSA (Prostate-Specific Antigen) Response
Description
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)
Title
Time to Pain Progression
Description
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)
Title
Pain Response
Description
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)

10. Eligibility

Sex
Male
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility 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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
ICD
Organizational Affiliation
Sanofi
Official's Role
Study Director
Facility Information:
Facility Name
sanofi-aventis US
City
Bridgewater
State/Province
New Jersey
ZIP/Postal Code
08807
Country
United States
Facility Name
sanofi-aventis Argentina
City
Buenos Aires
Country
Argentina
Facility Name
sanofi-aventis Belgium
City
Diegem
Country
Belgium
Facility Name
sanofi-aventis Brazil
City
Sao Paulo
Country
Brazil
Facility Name
sanofi-aventis Canada
City
Laval
State/Province
Quebec
Country
Canada
Facility Name
sanofi-aventis Chile
City
Santiago
Country
Chile
Facility Name
sanofi-aventis Czech Republic
City
Praha
Country
Czech Republic
Facility Name
sanofi-aventis Denmark
City
Horsholm
Country
Denmark
Facility Name
sanofi-aventis Finland
City
Helsinki
Country
Finland
Facility Name
sanofi-aventis France
City
Paris
Country
France
Facility Name
sanofi-aventis Germany
City
Berlin
Country
Germany
Facility Name
Sanofi-Aventis Hungaria
City
Budapest
Country
Hungary
Facility Name
sanofi-aventis India
City
Mumbai
Country
India
Facility Name
sanofi-aventis Italy
City
Milano
Country
Italy
Facility Name
sanofi-aventis South Korea
City
Seoul
Country
Korea, Republic of
Facility Name
sanofi-aventis Mexico
City
Mexico
Country
Mexico
Facility Name
sanofi-aventis Netherlands
City
Gouda
Country
Netherlands
Facility Name
sanofi-aventis Russia
City
Moscow
Country
Russian Federation
Facility Name
sanofi-aventis Singapore
City
Singapore
Country
Singapore
Facility Name
sanofi-aventis Slovakia
City
Bratislava
Country
Slovakia
Facility Name
sanofi-aventis South Africa
City
Midrand
Country
South Africa
Facility Name
sanofi-aventis Spain
City
Barcelona
Country
Spain
Facility Name
sanofi-aventis Sweden
City
Bromma
Country
Sweden
Facility Name
sanofi-aventis Taiwan
City
Taipei
Country
Taiwan
Facility Name
sanofi-aventis Turkey
City
Istanbul
Country
Turkey
Facility Name
sanofi-aventis UK
City
Guildford
State/Province
Surrey
Country
United Kingdom

12. IPD Sharing Statement

Citations:
PubMed Identifier
25538172
Citation
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.
Results Reference
derived
PubMed Identifier
23723295
Citation
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.
Results Reference
derived
PubMed Identifier
22743148
Citation
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.
Results Reference
derived
PubMed Identifier
20888992
Citation
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.
Results Reference
derived

Learn more about this trial

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

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