Trial Review

Did you know?

The ANZCTR now automatically displays published trial results and simplifies the addition of trial documents such as unpublished protocols and statistical analysis plans.

These enhancements will offer a more comprehensive view of trials, regardless of whether their results are positive, negative, or inconclusive.

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers
Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT01568866




Registration number
NCT01568866
Ethics application status
Date submitted
28/03/2012
Date registered
2/04/2012
Date last updated
14/11/2022

Titles & IDs
Public title
Phase 3 Study With Carfilzomib and Dexamethasone Versus Bortezomib and Dexamethasone for Relapsed Multiple Myeloma Patients
Scientific title
A Randomized, Open-label, Phase 3 Study of Carfilzomib Plus Dexamethasone vs. Bortezomib Plus Dexamethasone in Patients With Relapsed Multiple Myeloma
Secondary ID [1] 0 0
2012-000128-16
Secondary ID [2] 0 0
2011-003
Universal Trial Number (UTN)
Trial acronym
ENDEAVOR
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Multiple Myeloma 0 0
Condition category
Condition code
Cancer 0 0 0 0
Other cancer types

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Carfilzomib
Treatment: Drugs - Bortezomib
Treatment: Drugs - Dexamethasone

Experimental: Carfilzomib plus Dexamethasone - Participants received 20 mg/m² carfilzomib administered by intravenous (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.

Active comparator: Bortezomib plus Dexamethasone - Participants received bortezomib 1.3 mg/m² administered IV or subcutaneously (SC) on Days 1, 4, 8, and 11 of a 21-day cycle plus dexamethasone 20 mg administered on Days 1, 2, 4, 5, 8, 9, 11, and 12 of each 21-day cycle.


Treatment: Drugs: Carfilzomib
Carfilzomib is administered over 30 minutes as an infusion.

Treatment: Drugs: Bortezomib
Bortezomib is administered as a 3-5 second bolus IV injection or SC injection (in accordance with regulatory approval)

Treatment: Drugs: Dexamethasone
Tablet for oral administration; On days when carfilzomib or bortezomib was administered, the dexamethasone was to be given 30 minutes to 4 hours prior to the carfilzomib or bortezomib dose.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Progression-free Survival
Timepoint [1] 0 0
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
Secondary outcome [1] 0 0
Overall Survival
Timepoint [1] 0 0
From randomization until the data cut-off date of 03 January 2017; median follow-up time for OS was 36.9 and 37.5 months for each treatment group respectively.
Secondary outcome [2] 0 0
Overall Response
Timepoint [2] 0 0
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.
Secondary outcome [3] 0 0
Duration of Response
Timepoint [3] 0 0
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.
Secondary outcome [4] 0 0
Percentage of Participants With = Grade 2 Peripheral Neuropathy
Timepoint [4] 0 0
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.
Secondary outcome [5] 0 0
Percentage of Participants With a Significant Reduction in Left Ventricular Ejection Fraction (LVEF)
Timepoint [5] 0 0
Baseline and 24 weeks
Secondary outcome [6] 0 0
Change From Baseline in Right Ventricular Fractional Area Change (FAC)
Timepoint [6] 0 0
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).
Secondary outcome [7] 0 0
Change From Baseline in Pulmonary Artery Systolic Pressure (PASP)
Timepoint [7] 0 0
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).

Eligibility
Key inclusion criteria
1. Multiple myeloma with relapsing or progressing disease at study entry.
2. Patients must have evaluable multiple myeloma with, at least one of the following (assessed within 21 days prior to randomization):

* Serum M-protein = 0.5 g/dL, or
* Urine M-protein = 200 mg/24 hour, or
* In patients without detectable serum or urine M-protein, serum free light chain (SFLC) > 100 mg/L (involved light chain) and an abnormal serum kappa/lamda ratio, or
* For immunoglobulin (Ig) A patients whose disease can only be reliably measured by serum quantitative immunoglobulin (qIgA) = 750 mg/dL (0.75 g/dL).
3. Patients must have documented at least partial response (PR) to at least 1 line of prior therapy. PR documentation can be based on Investigator assessment.
4. Received 1, but no more than 3 prior treatment regimens or lines of therapy for multiple myeloma. (Induction therapy followed by stem cell transplant and consolidation/maintenance therapy will be considered as one line of therapy).
5. Prior therapy with Velcade is allowed as long as the patient had at least a PR to prior Velcade therapy, was not removed from Velcade therapy due to toxicity, and will have at least a 6 month Velcade treatment-free interval from last dose received until first study treatment. (Patients may receive maintenance therapy with drugs that are not in the proteasome inhibitor class during this 6 month Velcade treatment-free interval).
6. Prior therapy with carfilzomib is allowed as long as the patient had at least a PR to prior carfilzomib therapy, was not removed from carfilzomib therapy due to toxicity, and had at least a 6-month carfilzomib treatment-free interval from last dose received until first study treatment. (Patients may receive maintenance therapy with drugs that are not in the proteasome inhibitor class during this 6 month carfilzomib treatment-free interval). The exception to this is patients randomized or previously randomized in any other Onyx-Sponsored Phase 3 trial.
7. Males and females = 18 years of age.
8. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 to 2.
9. Adequate hepatic function within 21 days prior to randomization, with bilirubin < 1.5 times the upper limit of normal (ULN), and aspartate aminotransferase (AST) and alanine aminotransferase (ALT) < 3 times the ULN.
10. Left ventricular ejection fraction (LVEF) = 40%.
11. Absolute neutrophil count (ANC) = 1000/mm³ within 21 days prior to randomization. Screening ANC should be independent of growth factor support for = 1 week.
12. Hemoglobin = 8.0 g/dL within 21 days prior to randomization. Use of erythropoietic stimulating factors and red blood cell (RBC) transfusions per institutional guidelines is allowed, however most recent RBC transfusion may not have been done within 7 days prior to obtaining screening hemoglobin.
13. Platelet count = 50,000/mm³ (= 30,000/mm³ if myeloma involvement in the bone marrow is > 50%) within 21 days prior to randomization. Patients should not have received platelet transfusions for at least 1 week prior to obtaining the screening platelet count.
14. Calculated or measured creatinine clearance (CrCl) of = 15 mL/min within 21 days prior to randomization. Calculation should be based on standard formula such as the Cockcroft and Gault:

[(140 - Age) x Mass (kg) / (72 x Creatinine mg/dL)]; multiply result by 0.85 if female.
15. Written informed consent in accordance with federal, local, and institutional guidelines.
16. Female patients of child-bearing potential (FCBP) must have a negative serum pregnancy test within 21 days prior to randomization and agree to use an effective method of contraception during and for 3 months following last dose of drug (more frequent pregnancy tests may be conducted if required per local regulations). FCBP is defined as a sexually mature woman who: 1) has not undergone a hysterectomy or bilateral oophorectomy or 2) has not been naturally postmenopausal (amenorrhea following cancer therapy does not rule out childbearing potential) for at least 12 consecutive months (i.e., has had menses at any time in the preceding 12 consecutive months).
17. Male patients must use an effective barrier method of contraception during study and for 3 months following the last dose if sexually active with a FCBP.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Multiple Myeloma of IgM subtype.
2. Glucocorticoid therapy (prednisone > 30 mg/day or equivalent) within 14 days prior to randomization.
3. POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes).
4. Plasma cell leukemia or circulating plasma cells = 2 × 10^9/L.
5. Waldenstrom's Macroglobulinemia.
6. Patients with known amyloidosis.
7. Chemotherapy with approved or investigational anticancer therapeutics within 21 days prior to randomization.
8. Patients randomized or previously randomized in any other Onyx-Sponsored Phase 3 trial.
9. Focal radiation therapy within 7 days prior to randomization. Radiation therapy to an extended field involving a significant volume of bone marrow within 21 days prior to randomization (i.e., prior radiation must have been to less than 30% of the bone marrow).
10. Immunotherapy within 21 days prior to randomization.
11. Major surgery (excluding kyphoplasty) within 28 days prior to randomization.
12. Active congestive heart failure (New York Heart Association [NYHA] Class III to IV), symptomatic ischemia, or conduction abnormalities uncontrolled by conventional intervention. Myocardial infarction within four months prior to randomization.
13. Acute active infection requiring systemic antibiotics, antiviral (except antiviral therapy directed at hepatitis B) or antifungal agents within 14 days prior to randomization.
14. Known human immunodeficiency (HIV) seropositive, hepatitis C infection, and/or hepatitis B (except for patients with hepatitis B surface antigen [SAg] or core antibody receiving and responding to antiviral therapy directed at hepatitis B: these patients are allowed).
15. Patients with known cirrhosis.
16. Second malignancy within the past 3 years except:

* adequately treated basal cell or squamous cell skin cancer
* carcinoma in situ of the cervix
* prostate cancer < Gleason score 6 with stable prostate-specific antigen (PSA) over 12 months
* breast carcinoma in situ with full surgical resection
* treated medullary or papillary thyroid cancer
17. Patients with myelodysplastic syndrome.
18. Significant neuropathy (Grades 3 to 4, or Grade 2 with pain) within 14 days prior to randomization.
19. Female patients who are pregnant or lactating.
20. Known history of allergy to Captisol(a cyclodextrin derivative used to solubilize carfilzomib).
21. Patients with hypersensitivity to carfilzomib, Velcade, boron, or mannitol.
22. Patients with contraindication to dexamethasone.
23. Contraindication to any of the required concomitant drugs or supportive treatments, including hypersensitivity to antiviral drugs, or intolerance to hydration due to preexisting pulmonary or cardiac impairment.
24. Ongoing graft-vs-host disease.
25. Patients with pleural effusions requiring thoracentesis or ascites requiring paracentesis within 14 days prior to randomization.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
20/06/2012
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
5/02/2018
Sample size
Target
Accrual to date
Final
929
Recruitment in Australia
Recruitment state(s)
NSW,QLD,SA,VIC,WA
Recruitment hospital [1] 0 0
Royal Prince Alfred Hospital - Camperdown
Recruitment hospital [2] 0 0
St. Vincent's Public Hospital Sydney - Darlinghurst
Recruitment hospital [3] 0 0
Saint George Hospital - Kogarah
Recruitment hospital [4] 0 0
Liverpool Hospital - Liverpool
Recruitment hospital [5] 0 0
Royal North Shore Hospital - Saint Leonards
Recruitment hospital [6] 0 0
Calvary Mater Newcastle - Waratah
Recruitment hospital [7] 0 0
Westmead Hospital - Westmead
Recruitment hospital [8] 0 0
Royal Brisbane and Women's Hospital - Herston
Recruitment hospital [9] 0 0
Haematology & Oncology Clinics of Australia - South Brisbane
Recruitment hospital [10] 0 0
Haematology and Oncology Clinics of Australia at Chermside - South Brisbane
Recruitment hospital [11] 0 0
Haematology and Oncology Clinics of Australia at Wesley - South Brisbane
Recruitment hospital [12] 0 0
Royal Adelaide Hospital - Adelaide
Recruitment hospital [13] 0 0
The Queen Elizabeth Hospital - Woodville
Recruitment hospital [14] 0 0
Box Hill Hospital - Box Hill
Recruitment hospital [15] 0 0
Monash Medical Centre - Clayton
Recruitment hospital [16] 0 0
Saint Vincent's Hospital - East Melbourne
Recruitment hospital [17] 0 0
Western Hospital - Footscray
Recruitment hospital [18] 0 0
The Alfred Hospital - Melbourne
Recruitment hospital [19] 0 0
Sunshine Hospital - St. Albans
Recruitment hospital [20] 0 0
Fremantle Hospital - Fremantle
Recruitment hospital [21] 0 0
Royal Perth Hospital - Perth
Recruitment postcode(s) [1] 0 0
- Camperdown
Recruitment postcode(s) [2] 0 0
- Darlinghurst
Recruitment postcode(s) [3] 0 0
- Kogarah
Recruitment postcode(s) [4] 0 0
- Liverpool
Recruitment postcode(s) [5] 0 0
- Saint Leonards
Recruitment postcode(s) [6] 0 0
- Waratah
Recruitment postcode(s) [7] 0 0
- Westmead
Recruitment postcode(s) [8] 0 0
- Herston
Recruitment postcode(s) [9] 0 0
- South Brisbane
Recruitment postcode(s) [10] 0 0
- Adelaide
Recruitment postcode(s) [11] 0 0
- Woodville
Recruitment postcode(s) [12] 0 0
- Box Hill
Recruitment postcode(s) [13] 0 0
- Clayton
Recruitment postcode(s) [14] 0 0
- East Melbourne
Recruitment postcode(s) [15] 0 0
- Footscray
Recruitment postcode(s) [16] 0 0
- Melbourne
Recruitment postcode(s) [17] 0 0
- St. Albans
Recruitment postcode(s) [18] 0 0
- Fremantle
Recruitment postcode(s) [19] 0 0
- Perth
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Colorado
Country [3] 0 0
United States of America
State/province [3] 0 0
Florida
Country [4] 0 0
United States of America
State/province [4] 0 0
Georgia
Country [5] 0 0
United States of America
State/province [5] 0 0
Indiana
Country [6] 0 0
United States of America
State/province [6] 0 0
Maryland
Country [7] 0 0
United States of America
State/province [7] 0 0
Michigan
Country [8] 0 0
United States of America
State/province [8] 0 0
Missouri
Country [9] 0 0
United States of America
State/province [9] 0 0
New Jersey
Country [10] 0 0
United States of America
State/province [10] 0 0
New York
Country [11] 0 0
United States of America
State/province [11] 0 0
North Carolina
Country [12] 0 0
United States of America
State/province [12] 0 0
Ohio
Country [13] 0 0
United States of America
State/province [13] 0 0
Pennsylvania
Country [14] 0 0
United States of America
State/province [14] 0 0
South Carolina
Country [15] 0 0
United States of America
State/province [15] 0 0
Tennessee
Country [16] 0 0
United States of America
State/province [16] 0 0
Texas
Country [17] 0 0
United States of America
State/province [17] 0 0
Utah
Country [18] 0 0
Austria
State/province [18] 0 0
Tyrol
Country [19] 0 0
Austria
State/province [19] 0 0
Upper Austria
Country [20] 0 0
Austria
State/province [20] 0 0
Vienna
Country [21] 0 0
Belgium
State/province [21] 0 0
Flemish Brabant
Country [22] 0 0
Belgium
State/province [22] 0 0
Namur
Country [23] 0 0
Belgium
State/province [23] 0 0
Oost-vlaanderen
Country [24] 0 0
Belgium
State/province [24] 0 0
Antwerp
Country [25] 0 0
Belgium
State/province [25] 0 0
Brussels
Country [26] 0 0
Brazil
State/province [26] 0 0
RIO Grande DO Norte
Country [27] 0 0
Brazil
State/province [27] 0 0
RIO Grande DO SUL
Country [28] 0 0
Brazil
State/province [28] 0 0
SAO Paulo
Country [29] 0 0
Brazil
State/province [29] 0 0
Rio de Janeiro
Country [30] 0 0
Brazil
State/province [30] 0 0
São Paulo
Country [31] 0 0
Bulgaria
State/province [31] 0 0
Sofiya
Country [32] 0 0
Bulgaria
State/province [32] 0 0
Plovdiv
Country [33] 0 0
Bulgaria
State/province [33] 0 0
Varna
Country [34] 0 0
Canada
State/province [34] 0 0
Alberta
Country [35] 0 0
Canada
State/province [35] 0 0
British Columbia
Country [36] 0 0
Canada
State/province [36] 0 0
New Brunswick
Country [37] 0 0
Canada
State/province [37] 0 0
Nova Scotia
Country [38] 0 0
Canada
State/province [38] 0 0
Ontario
Country [39] 0 0
Canada
State/province [39] 0 0
Quebec
Country [40] 0 0
Czechia
State/province [40] 0 0
Praha
Country [41] 0 0
Czechia
State/province [41] 0 0
Severomoravsky KRAJ
Country [42] 0 0
Czechia
State/province [42] 0 0
Vychodocesky KRAJ
Country [43] 0 0
Czechia
State/province [43] 0 0
Brno
Country [44] 0 0
France
State/province [44] 0 0
Aquitaine
Country [45] 0 0
France
State/province [45] 0 0
Bretagne
Country [46] 0 0
France
State/province [46] 0 0
Cedex 1
Country [47] 0 0
France
State/province [47] 0 0
Haute-normandie
Country [48] 0 0
France
State/province [48] 0 0
Ile-de-france
Country [49] 0 0
France
State/province [49] 0 0
NORD Pas-de-calais
Country [50] 0 0
France
State/province [50] 0 0
PAYS DE LA Loire
Country [51] 0 0
France
State/province [51] 0 0
Provence Alpes COTE D'azur
Country [52] 0 0
France
State/province [52] 0 0
Rhone-alpes
Country [53] 0 0
Germany
State/province [53] 0 0
Baden-wuerttemberg
Country [54] 0 0
Germany
State/province [54] 0 0
Bayern
Country [55] 0 0
Germany
State/province [55] 0 0
Niedersachsen
Country [56] 0 0
Germany
State/province [56] 0 0
Nordrhein-westfalen
Country [57] 0 0
Germany
State/province [57] 0 0
Rheinland-pfalz
Country [58] 0 0
Germany
State/province [58] 0 0
Saarland
Country [59] 0 0
Germany
State/province [59] 0 0
Sachsen
Country [60] 0 0
Germany
State/province [60] 0 0
Thuringen
Country [61] 0 0
Germany
State/province [61] 0 0
Freiburg
Country [62] 0 0
Germany
State/province [62] 0 0
Hamburg
Country [63] 0 0
Greece
State/province [63] 0 0
Attica
Country [64] 0 0
Hungary
State/province [64] 0 0
Bacs-kiskun
Country [65] 0 0
Hungary
State/province [65] 0 0
Baranya
Country [66] 0 0
Hungary
State/province [66] 0 0
Csongrad
Country [67] 0 0
Hungary
State/province [67] 0 0
Hajdu-bihar
Country [68] 0 0
Hungary
State/province [68] 0 0
Budapest
Country [69] 0 0
Hungary
State/province [69] 0 0
Kaposvár
Country [70] 0 0
Israel
State/province [70] 0 0
Haifa
Country [71] 0 0
Israel
State/province [71] 0 0
Jerusalem
Country [72] 0 0
Israel
State/province [72] 0 0
Kfar Saba
Country [73] 0 0
Israel
State/province [73] 0 0
Tel Aviv
Country [74] 0 0
Israel
State/province [74] 0 0
Tel Hashomer
Country [75] 0 0
Italy
State/province [75] 0 0
Potenza
Country [76] 0 0
Italy
State/province [76] 0 0
Torino
Country [77] 0 0
Italy
State/province [77] 0 0
Ancona
Country [78] 0 0
Italy
State/province [78] 0 0
Bologna
Country [79] 0 0
Italy
State/province [79] 0 0
Brescia
Country [80] 0 0
Italy
State/province [80] 0 0
Genova
Country [81] 0 0
Italy
State/province [81] 0 0
Novara
Country [82] 0 0
Italy
State/province [82] 0 0
Piacenza
Country [83] 0 0
Italy
State/province [83] 0 0
Pisa
Country [84] 0 0
Italy
State/province [84] 0 0
Roma
Country [85] 0 0
Italy
State/province [85] 0 0
Siena
Country [86] 0 0
Japan
State/province [86] 0 0
Aichi
Country [87] 0 0
Japan
State/province [87] 0 0
Fukuoka
Country [88] 0 0
Japan
State/province [88] 0 0
Gifu
Country [89] 0 0
Japan
State/province [89] 0 0
Gunma
Country [90] 0 0
Japan
State/province [90] 0 0
Hokkaido
Country [91] 0 0
Japan
State/province [91] 0 0
Hyogo
Country [92] 0 0
Japan
State/province [92] 0 0
Kanagawa
Country [93] 0 0
Japan
State/province [93] 0 0
Niigata
Country [94] 0 0
Japan
State/province [94] 0 0
Osaka
Country [95] 0 0
Japan
State/province [95] 0 0
Saitama
Country [96] 0 0
Japan
State/province [96] 0 0
Tochigi
Country [97] 0 0
Japan
State/province [97] 0 0
Tokyo
Country [98] 0 0
Japan
State/province [98] 0 0
Kyoto
Country [99] 0 0
Japan
State/province [99] 0 0
Okayama
Country [100] 0 0
Japan
State/province [100] 0 0
Tokushima
Country [101] 0 0
Korea, Republic of
State/province [101] 0 0
Gyeonggi-Do
Country [102] 0 0
Korea, Republic of
State/province [102] 0 0
Gyeonggi-do
Country [103] 0 0
Korea, Republic of
State/province [103] 0 0
Gyeongsangnam-Do
Country [104] 0 0
Korea, Republic of
State/province [104] 0 0
Daegu
Country [105] 0 0
Korea, Republic of
State/province [105] 0 0
Seoul
Country [106] 0 0
New Zealand
State/province [106] 0 0
Auckland
Country [107] 0 0
New Zealand
State/province [107] 0 0
Aukland
Country [108] 0 0
New Zealand
State/province [108] 0 0
Christchurch
Country [109] 0 0
New Zealand
State/province [109] 0 0
Dunedin
Country [110] 0 0
Poland
State/province [110] 0 0
Kujawsko-Pomorskie
Country [111] 0 0
Poland
State/province [111] 0 0
Lubelskie
Country [112] 0 0
Poland
State/province [112] 0 0
Malopolskie
Country [113] 0 0
Poland
State/province [113] 0 0
Mazowieckie
Country [114] 0 0
Poland
State/province [114] 0 0
Pomorskie
Country [115] 0 0
Poland
State/province [115] 0 0
Slaskie
Country [116] 0 0
Poland
State/province [116] 0 0
Wielkopolskie
Country [117] 0 0
Romania
State/province [117] 0 0
Bucuresti
Country [118] 0 0
Romania
State/province [118] 0 0
Brasov
Country [119] 0 0
Romania
State/province [119] 0 0
Iasi
Country [120] 0 0
Russian Federation
State/province [120] 0 0
Izhevsk
Country [121] 0 0
Russian Federation
State/province [121] 0 0
Moscow
Country [122] 0 0
Russian Federation
State/province [122] 0 0
Ryazan
Country [123] 0 0
Russian Federation
State/province [123] 0 0
Saint Petersburg
Country [124] 0 0
Russian Federation
State/province [124] 0 0
Samara
Country [125] 0 0
Singapore
State/province [125] 0 0
Singapore
Country [126] 0 0
Slovakia
State/province [126] 0 0
Bratislava
Country [127] 0 0
Spain
State/province [127] 0 0
Baleares
Country [128] 0 0
Spain
State/province [128] 0 0
Barcelona
Country [129] 0 0
Spain
State/province [129] 0 0
Madrid
Country [130] 0 0
Spain
State/province [130] 0 0
Salamanca
Country [131] 0 0
Spain
State/province [131] 0 0
Sevilla
Country [132] 0 0
Spain
State/province [132] 0 0
Valencia
Country [133] 0 0
Taiwan
State/province [133] 0 0
Kaohsiung
Country [134] 0 0
Taiwan
State/province [134] 0 0
Taichung
Country [135] 0 0
Taiwan
State/province [135] 0 0
Tainan
Country [136] 0 0
Taiwan
State/province [136] 0 0
Taipei
Country [137] 0 0
Taiwan
State/province [137] 0 0
Tao-Yuan
Country [138] 0 0
Thailand
State/province [138] 0 0
Bangkok Metropolis
Country [139] 0 0
Thailand
State/province [139] 0 0
Khon Kaen
Country [140] 0 0
Ukraine
State/province [140] 0 0
Dnipropretrovsk
Country [141] 0 0
Ukraine
State/province [141] 0 0
Kharkiv
Country [142] 0 0
Ukraine
State/province [142] 0 0
Cherkassy
Country [143] 0 0
Ukraine
State/province [143] 0 0
Dnipropetrovsk
Country [144] 0 0
Ukraine
State/province [144] 0 0
Donetsk
Country [145] 0 0
Ukraine
State/province [145] 0 0
Khmelnytsky
Country [146] 0 0
Ukraine
State/province [146] 0 0
Kiev
Country [147] 0 0
Ukraine
State/province [147] 0 0
Kyiv
Country [148] 0 0
Ukraine
State/province [148] 0 0
Lviv
Country [149] 0 0
Ukraine
State/province [149] 0 0
Mykolayiv
Country [150] 0 0
United Kingdom
State/province [150] 0 0
England

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Amgen
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
The primary objective of this study was to compare progression-free survival in patients with multiple myeloma who relapsed after 1 to 3 prior therapies treated with carfilzomib plus dexamethasone or bortezomib plus dexamethasone.
Trial website
https://clinicaltrials.gov/study/NCT01568866
Trial related presentations / publications
Moreau P, Joshua D, Chng WJ, Palumbo A, Goldschmidt H, Hajek R, Facon T, Ludwig H, Pour L, Niesvizky R, Oriol A, Rosinol L, Suvorov A, Gaidano G, Pika T, Weisel K, Goranova-Marinova V, Gillenwater HH, Mohamed N, Aggarwal S, Feng S, Dimopoulos MA. Impact of prior treatment on patients with relapsed multiple myeloma treated with carfilzomib and dexamethasone vs bortezomib and dexamethasone in the phase 3 ENDEAVOR study. Leukemia. 2017 Jan;31(1):115-122. doi: 10.1038/leu.2016.186. Epub 2016 Jul 4.
Chng WJ, Goldschmidt H, Dimopoulos MA, Moreau P, Joshua D, Palumbo A, Facon T, Ludwig H, Pour L, Niesvizky R, Oriol A, Rosinol L, Suvorov A, Gaidano G, Pika T, Weisel K, Goranova-Marinova V, Gillenwater HH, Mohamed N, Feng S, Aggarwal S, Hajek R. Carfilzomib-dexamethasone vs bortezomib-dexamethasone in relapsed or refractory multiple myeloma by cytogenetic risk in the phase 3 study ENDEAVOR. Leukemia. 2017 Jun;31(6):1368-1374. doi: 10.1038/leu.2016.390. Epub 2016 Dec 27.
Dimopoulos MA, Goldschmidt H, Niesvizky R, Joshua D, Chng WJ, Oriol A, Orlowski RZ, Ludwig H, Facon T, Hajek R, Weisel K, Hungria V, Minuk L, Feng S, Zahlten-Kumeli A, Kimball AS, Moreau P. Carfilzomib or bortezomib in relapsed or refractory multiple myeloma (ENDEAVOR): an interim overall survival analysis of an open-label, randomised, phase 3 trial. Lancet Oncol. 2017 Oct;18(10):1327-1337. doi: 10.1016/S1470-2045(17)30578-8. Epub 2017 Aug 23. Erratum In: Lancet Oncol. 2017 Oct;18(10):e562. doi: 10.1016/S1470-2045(17)30721-0.
Ludwig H, Dimopoulos MA, Moreau P, Chng WJ, Goldschmidt H, Hajek R, Facon T, Pour L, Niesvizky R, Oriol A, Rosinol L, Suvorov A, Gaidano G, Pika T, Weisel K, Goranova-Marinova V, Palumbo A, Gillenwater HH, Mohamed N, Aggarwal S, Feng S, Joshua D. Carfilzomib and dexamethasone vs bortezomib and dexamethasone in patients with relapsed multiple myeloma: results of the phase 3 study ENDEAVOR (NCT01568866) according to age subgroup. Leuk Lymphoma. 2017 Oct;58(10):2501-2504. doi: 10.1080/10428194.2017.1298755. Epub 2017 Mar 17. No abstract available.
Chari A, Stewart AK, Russell SD, Moreau P, Herrmann J, Banchs J, Hajek R, Groarke J, Lyon AR, Batty GN, Ro S, Huang M, Iskander KS, Lenihan D. Analysis of carfilzomib cardiovascular safety profile across relapsed and/or refractory multiple myeloma clinical trials. Blood Adv. 2018 Jul 10;2(13):1633-1644. doi: 10.1182/bloodadvances.2017015545.
Dimopoulos M, Siegel D, White DJ, Boccia R, Iskander KS, Yang Z, Kimball AS, Mezzi K, Ludwig H, Niesvizky R. Carfilzomib vs bortezomib in patients with multiple myeloma and renal failure: a subgroup analysis of ENDEAVOR. Blood. 2019 Jan 10;133(2):147-155. doi: 10.1182/blood-2018-06-860015. Epub 2018 Nov 26.
Facon T, Niesvizky R, Mateos MV, Siegel D, Rosenbaum C, Bringhen S, Weisel K, Ho PJ, Ludwig H, Kumar S, Wang K, Obreja M, Yang Z, Klippel Z, Mezzi K, Goldrick A, Tekle C, Dimopoulos MA. Efficacy and safety of carfilzomib-based regimens in frail patients with relapsed and/or refractory multiple myeloma. Blood Adv. 2020 Nov 10;4(21):5449-5459. doi: 10.1182/bloodadvances.2020001965.
Hari P, Mateos MV, Abonour R, Knop S, Bensinger W, Ludwig H, Song K, Hajek R, Moreau P, Siegel DS, Feng S, Obreja M, Aggarwal SK, Iskander K, Goldschmidt H. Efficacy and safety of carfilzomib regimens in multiple myeloma patients relapsing after autologous stem cell transplant: ASPIRE and ENDEAVOR outcomes. Leukemia. 2017 Dec;31(12):2630-2641. doi: 10.1038/leu.2017.122. Epub 2017 Apr 25.
Leleu X, Martin TG, Einsele H, Lyons RM, Durie BGM, Iskander KS, Ailawadhi S. Role of Proteasome Inhibitors in Relapsed and/or Refractory Multiple Myeloma. Clin Lymphoma Myeloma Leuk. 2019 Jan;19(1):9-22. doi: 10.1016/j.clml.2018.08.016. Epub 2018 Sep 5.
Ludwig H, Moreau P, Dimopoulos MA, Mateos MV, Kaiser M, Hajek R, Feng S, Cocks K, Buchanan J, Weisel K. Health-related quality of life in the ENDEAVOR study: carfilzomib-dexamethasone vs bortezomib-dexamethasone in relapsed/refractory multiple myeloma. Blood Cancer J. 2019 Feb 22;9(3):23. doi: 10.1038/s41408-019-0181-0.
Mateos MV, Goldschmidt H, San-Miguel J, Mikhael J, DeCosta L, Zhou L, Obreja M, Blaedel J, Szabo Z, Leleu X. Carfilzomib in relapsed or refractory multiple myeloma patients with early or late relapse following prior therapy: A subgroup analysis of the randomized phase 3 ASPIRE and ENDEAVOR trials. Hematol Oncol. 2018 Apr;36(2):463-470. doi: 10.1002/hon.2499. Epub 2018 Feb 15.
Moreau P, Stewart KA, Dimopoulos M, Siegel D, Facon T, Berenson J, Raje N, Berdeja JG, Orlowski RZ, Yang H, Ma H, Klippel Z, Zahlten-Kumeli A, Mezzi K, Iskander K, Mateos MV. Once-weekly (70 mg/m2 ) vs twice-weekly (56 mg/m2 ) dosing of carfilzomib in patients with relapsed or refractory multiple myeloma: A post hoc analysis of the ENDEAVOR, A.R.R.O.W., and CHAMPION-1 trials. Cancer Med. 2020 May;9(9):2989-2996. doi: 10.1002/cam4.2945. Epub 2020 Feb 28.
Dimopoulos MA, Moreau P, Iida S, Huang SY, Takezako N, Chng WJ, Zahlten-Kumeli A, Sersch MA, Li J, Huang M, Lee JH. Outcomes for Asian patients with multiple myeloma receiving once- or twice-weekly carfilzomib-based therapy: a subgroup analysis of the randomized phase 3 ENDEAVOR and A.R.R.O.W. Trials. Int J Hematol. 2019 Oct;110(4):466-473. doi: 10.1007/s12185-019-02704-z. Epub 2019 Aug 6.
Goldschmidt H, Moreau P, Ludwig H, Niesvizky R, Chng WJ, Joshua D, Weisel K, Spencer A, Orlowski RZ, Feng S, Iskander KS, Dimopoulos MA. Carfilzomib-dexamethasone versus subcutaneous or intravenous bortezomib in relapsed or refractory multiple myeloma: secondary analysis of the phase 3 ENDEAVOR study. Leuk Lymphoma. 2018 Jun;59(6):1364-1374. doi: 10.1080/10428194.2017.1376743. Epub 2017 Sep 22.
Jakubowiak AJ, Houisse I, Majer I, Benedict A, Campioni M, Panjabi S, Ailawadhi S. Cost-effectiveness of carfilzomib plus dexamethasone compared with bortezomib plus dexamethasone for patients with relapsed or refractory multiple myeloma in the United States. Expert Rev Hematol. 2017 Dec;10(12):1107-1119. doi: 10.1080/17474086.2017.1391088.
Weisel K, Mateos MV, Gay F, Delforge M, Cook G, Szabo Z, Desgraz R, DeCosta L, Moreau P. Efficacy and safety profile of deep responders to carfilzomib-based therapy: a subgroup analysis from ASPIRE and ENDEAVOR. Leukemia. 2021 Jun;35(6):1732-1744. doi: 10.1038/s41375-020-01049-5. Epub 2020 Oct 16.
Weisel K, Majer I, DeCosta L, Oriol A, Goldschmidt H, Ludwig H, Campioni M, Szabo Z, Dimopoulos M. Carfilzomib and dexamethasone versus eight cycles of bortezomib and dexamethasone in patients with relapsed or refractory multiple myeloma: an indirect comparison using data from the phase 3 ENDEAVOR and CASTOR trials. Leuk Lymphoma. 2020 Jan;61(1):37-46. doi: 10.1080/10428194.2019.1648806. Epub 2019 Oct 22.
Orlowski RZ, Moreau P, Niesvizky R, Ludwig H, Oriol A, Chng WJ, Goldschmidt H, Yang Z, Kimball AS, Dimopoulos M. Carfilzomib-Dexamethasone Versus Bortezomib-Dexamethasone in Relapsed or Refractory Multiple Myeloma: Updated Overall Survival, Safety, and Subgroups. Clin Lymphoma Myeloma Leuk. 2019 Aug;19(8):522-530.e1. doi: 10.1016/j.clml.2019.04.018. Epub 2019 May 2.
Majer IM, Castaigne JG, Palmer S, DeCosta L, Campioni M. Modeling Covariate-Adjusted Survival for Economic Evaluations in Oncology. Pharmacoeconomics. 2019 May;37(5):727-737. doi: 10.1007/s40273-018-0759-6.
Rosenthal A, Luthi J, Belohlavek M, Kortum KM, Mookadam F, Mayo A, Fonseca R, Bergsagel PL, Reeder CB, Mikhael JR, Stewart AK. Carfilzomib and the cardiorenal system in myeloma: an endothelial effect? Blood Cancer J. 2016 Jan 15;6(1):e384. doi: 10.1038/bcj.2015.112.
Dimopoulos MA, Moreau P, Palumbo A, Joshua D, Pour L, Hajek R, Facon T, Ludwig H, Oriol A, Goldschmidt H, Rosinol L, Straub J, Suvorov A, Araujo C, Rimashevskaya E, Pika T, Gaidano G, Weisel K, Goranova-Marinova V, Schwarer A, Minuk L, Masszi T, Karamanesht I, Offidani M, Hungria V, Spencer A, Orlowski RZ, Gillenwater HH, Mohamed N, Feng S, Chng WJ; ENDEAVOR Investigators. Carfilzomib and dexamethasone versus bortezomib and dexamethasone for patients with relapsed or refractory multiple myeloma (ENDEAVOR): a randomised, phase 3, open-label, multicentre study. Lancet Oncol. 2016 Jan;17(1):27-38. doi: 10.1016/S1470-2045(15)00464-7. Epub 2015 Dec 5.
Public notes

Contacts
Principal investigator
Name 0 0
MD
Address 0 0
Amgen
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT01568866