Phase 3 Study With Carfilzomib and Dexamethasone Versus Bortezomib and Dexamethasone for Relapsed Multiple Myeloma Patients (ENDEAVOR)

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Onyx Pharmaceuticals
ClinicalTrials.gov Identifier:
NCT01568866
First received: March 28, 2012
Last updated: December 14, 2015
Last verified: December 2015
Results First Received: November 6, 2015  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Open Label;   Primary Purpose: Treatment
Condition: Multiple Myeloma
Interventions: Drug: Carfilzomib
Drug: Bortezomib
Drug: Dexamethasone

  Participant Flow
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
Adults with relapsed multiple myeloma were eligible to participate in this study. Participants were required to have relapsed or progressed multiple myeloma after at least 1, but no more than 3, prior multiple myeloma therapies.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
Results are reported as of the data cut-off date of 10 November 2014, at which time an interim analysis of the primary endpoint was performed after approximately 75% of the planned progression-free survival events had been observed. Monitoring for safety and long-term survival is continuing.

Reporting Groups
  Description
Bortezomib + DEX Participants received bortezomib 1.3 mg/m² administered intravenously (IV) or subcutaneously (SC) on Days 1, 4, 8, and 11 of a 21-day cycle plus dexamethasone (DEX) 20 mg administered on Days 1, 2, 4, 5, 8, 9, 11, and 12 of each 21-day cycle.
Carfilzomib + DEX Participants received 20 mg/m² carfilzomib administered by IV infusion on Days 1 and 2 of Cycle 1, followed by 56 mg/m² on Days 8, 9, 15, and 16 of Cycle 1 and for each 28-day cycle thereafter. Additionally, participants received 20 mg dexamethasone on Days 1, 2, 8, 9, 15, 16, 22, and 23 of each 28 day cycle.

Participant Flow:   Overall Study
    Bortezomib + DEX     Carfilzomib + DEX  
STARTED     465     464  
Received Treatment     456     463  
COMPLETED     105 [1]   200 [1]
NOT COMPLETED     360     264  
Disease Progression                 168                 117  
Adverse Event                 73                 65  
Patient Request                 45                 40  
Physician Decision                 35                 18  
Withdrawal by Subject                 19                 6  
Death                 9                 13  
Protocol Non-compliance                 1                 4  
Lost to Follow-up                 1                 0  
Randomized but Not Dosed                 9                 1  
[1] Indicates participants still receiving treatment



  Baseline Characteristics
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Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Intent-to-treat population (all randomized participants)

Reporting Groups
  Description
Bortezomib + DEX Participants received bortezomib 1.3 mg/m² administered intravenously (IV) or subcutaneously (SC) on Days 1, 4, 8, and 11 of a 21-day cycle plus dexamethasone (DEX) 20 mg administered on Days 1, 2, 4, 5, 8, 9, 11, and 12 of each 21-day cycle.
Carfilzomib + DEX Participants received 20 mg/m² carfilzomib administered by IV infusion on Days 1 and 2 of Cycle 1, followed by 56 mg/m² on Days 8, 9, 15, and 16 of Cycle 1 and for each 28-day cycle thereafter. Additionally, participants received 20 mg dexamethasone on Days 1, 2, 8, 9, 15, 16, 22, and 23 of each 28 day cycle.
Total Total of all reporting groups

Baseline Measures
    Bortezomib + DEX     Carfilzomib + DEX     Total  
Number of Participants  
[units: participants]
  465     464     929  
Age  
[units: years]
Median (Full Range)
  65.0   (30.0 to 88.0)     65.0   (35.0 to 89.0)     65.0   (30.0 to 89.0)  
Age, Customized  
[units: participants]
     
< 65 years     210     223     433  
65 -74 years     189     164     353  
≥ 75 years     66     77     143  
Gender  
[units: participants]
     
Female     236     224     460  
Male     229     240     469  
Race/Ethnicity, Customized  
[units: participants]
     
White     353     348     701  
Black     9     8     17  
Asian     57     56     113  
Native Hawaiian/Other Pacific Islander     0     2     2  
Not Reported     45     50     95  
Multiple     1     0     1  
Eastern Cooperative Oncology Group (ECOG) Performance Status [1]
[units: participants]
     
0 (Fully active)     232     221     453  
1 (Restrictive but ambulatory)     203     211     414  
2 (Ambulatory but unable to work)     30     32     62  
Stratification Factor: Prior Proteasome Inhibitor Treatment  
[units: participants]
     
Carfilzomib or bortezomib     253     252     505  
No prior carfilzomib or bortezomib     212     212     424  
Stratification Factor: Lines of Prior Treatment  
[units: participants]
     
1 line     229     231     460  
2 or 3 lines     236     233     469  
Stratification Factor: International Staging System (ISS) Stage [2]
[units: participants]
     
Stage I     204     205     409  
Stage II or III     261     259     520  
Stratification Factor: Route of Bortezomib Administration [3]
[units: participants]
     
Intravenous     108     108     216  
Subcutaneous     357     356     713  
[1] Eastern Cooperative Oncology Group (ECOG) Performance Status is used by doctors and researchers to assess how a participants disease is progressing, assess how the disease affects the daily living activities of the participant and determine appropriate treatment and prognosis. 0 = Fully Active; 1 = Restricted activity but ambulatory; 2 = Ambulatory but unable to carry out work activities; 3 = Limited Self-Care; 4 = Completely Disabled, no self-care, confined to bed or chair; 5 = Dead.
[2]

The International Staging System (ISS) for myeloma was published by the International Myeloma Working Group:

  • Stage I: β2-microglobulin (β2M) < 3.5 mg/L, albumin >= 3.5 g/dL
  • Stage II: β2M < 3.5 mg/L and albumin < 3.5 g/dL; or β2M 3.5 mg/L - 5.5 mg/L irrespective of the serum albumin
  • Stage III: β2M ≥ 5.5 mg/L
[3] The route of bortezomib administration (IV versus SC) was made in accordance with local regulatory approved route of administration. The value for this variable was selected for all participants prior to randomization to treatment group in order to balance the baseline characteristics that led to the choice of the particular route of bortezomib administration between the 2 arms.



  Outcome Measures
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1.  Primary:   Progression Free Survival   [ Time Frame: From randomization until the data cut-off date of 10 November 2014; median follow-up time for PFS was 11.1.and 11.9 months in the bortezomib and carfilzomib arms respectively ]

2.  Secondary:   Overall Survival   [ Time Frame: From randomization until the data cut-off date of 10 November 2014; median follow-up time for OS was 11.9 and 12.5 months for each treatment group respectively. ]

3.  Secondary:   Overall Response   [ Time Frame: Disease response was assessed every 28 days until end of treatment or the data cut-off date of 10 November 2014; median duration of treatment was 27 weeks in the bortezomib group and 40 weeks in the carfilzomib treatment group. ]

4.  Secondary:   Duration of Response   [ Time Frame: From randomization until the data cut-off date of 10 November 2014; median follow-up time for DOR was 9.4 and 10.4 months for each treatment group respectively. ]

5.  Secondary:   Percentage of Participants With ≥ Grade 2 Peripheral Neuropathy   [ Time Frame: From the first dose of study drug up to 30 days after the last dose of study drug as of the data cut-off date of 10 November 2014; median duration of treatment was 27 weeks in the bortezomib group and 40 weeks in the carfilzomib treatment group. ]

6.  Secondary:   Percentage of Participants With a Significant Reduction in Left Ventricular Ejection Fraction (LVEF)   [ Time Frame: Baseline and 24 weeks ]

7.  Secondary:   Change From Baseline in Right Ventricular Fractional Area Change (FAC)   [ Time Frame: Baseline and Weeks 12, 24 and 36 and at end of treatment (median duration of treatment was 27 weeks in the bortezomib group and 40 weeks in the carfilzomib treatment group). ]

8.  Secondary:   Change From Baseline in Pulmonary Artery Systolic Pressure (PASP)   [ Time Frame: Baseline and Weeks 12, 24 and 36 and at end of treatment (median duration of treatment was 27 weeks in the bortezomib group and 40 weeks in the carfilzomib treatment group). ]


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
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Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
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  More Information
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Certain Agreements:  
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The agreement is:
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.


Results Point of Contact:  
Name/Title: Study Director
Organization: Amgen, Inc.
phone: 866-572-6436


No publications provided


Responsible Party: Onyx Pharmaceuticals
ClinicalTrials.gov Identifier: NCT01568866     History of Changes
Other Study ID Numbers: 2011-003
2012-000128-16 ( EudraCT Number )
Study First Received: March 28, 2012
Results First Received: November 6, 2015
Last Updated: December 14, 2015
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