Now Available: Final Rule for FDAAA 801 and NIH Policy on Clinical Trial Reporting

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
  Hide Participant Flow

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
  Hide Baseline Characteristics

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 
Overall Participants Analyzed 
[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 
[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.
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 [1] 
[Units: Participants]
     
Stage I   204   205   409 
Stage II or III   261   259   520 
[1]

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
Stratification Factor: Route of Bortezomib Administration [1] 
[Units: Participants]
     
Intravenous   108   108   216 
Subcutaneous   357   356   713 
[1] 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
  Show All Outcome Measures

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
  Hide Limitations and Caveats

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
No text entered.


  More Information
  Hide More Information

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


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

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
Health Authority: United States: Institutional Review Board
United States: Food and Drug Administration
Canada: Health Canada
Austria : Federal Ministry for Labour, Health, and Social Affairs
Austria: Ethikkommission
Australia: Department of Health and Ageing Therapeutic Goods Administration
Australia: Human Research Ethics Committee
Belgium: Ethics Committee
Belgium: Federal Agency for Medicinal Products and Health Products
Brazil: Ethics Committee
Brazil: Ministry of Health
Bulgaria: Ethics committee
Bulgaria: Ministry of Health
Czech Republic: Ethics Committee
Czech Republic: State Institute for Drug Control
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
France: Institutional Ethical Committee
Germany: Ministry of Health
Germany: Ethics Commission
Greece: Ethics Committee
Greece: Ministry of Health and Welfare
Hungary: Institutional Ethics Committee
Hungary: National Institute for Quality and Organizational Development in Healthcare and Medicines
Israel: Ethics Commission
Italy: Ethics Committee
Italy: Ministry of Health
Japan: Institutional Review Board
Japan: Ministry of Health, Labor and Welfare
New Zealand: Ethics Committee
New Zealand: Medsafe
Poland: Ethics Committee
Poland: Ministry of Health
Romania: State Institute for Drug Control
Romania: Ethics Committee
Russia: Ethics Committee
Russia: Ministry of Health of the Russian Federation
Singapore: Health Sciences Authority
Singapore: Institutional Review Board
Slovakia: State Institute for Drug Control
Slovak Republic: Ethics Committee
South Korea: Institutional Review Board
South Korea: Korea Food and Drug Administration (KFDA)
Spain: Spanish Agency of Medicines
Spain: Ethics Committee
Taiwan: Department of Health
Taiwan: Research Ethics Committee
Thailand: Food and Drug Administration
Thailand: Institutional Review Board
Ukraine: Ministry of Health
Ukraine: Ethics Committee
United Kingdom: Medicines and Healthcare Products Regulatory Agency
United Kingdom: Research Ethics Committee