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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT01302392




Registration number
NCT01302392
Ethics application status
Date submitted
10/02/2011
Date registered
24/02/2011
Date last updated
2/05/2017

Titles & IDs
Public title
A Study of Carfilzomib vs Best Supportive Care in Subjects With Relapsed and Refractory Multiple Myeloma
Scientific title
A Randomized, Open-label, Phase 3 Study of Carfilzomib vs Best Supportive Care in Subjects With Relapsed and Refractory Multiple Myeloma
Secondary ID [1] 0 0
PX-171-011
Universal Trial Number (UTN)
Trial acronym
FOCUS
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 - Best Supportive Care

Active comparator: Best Supportive Care -

Experimental: Carfilzomib -


Treatment: Drugs: Carfilzomib
20mg/m² IV on Days 1 and 2 of Cycle 1, escalating to 27 mg/m² IV on Days 8,9,15,and 16 of Cycle 1 and continuing on Days 1,2,8,9,15,and 16 of Cycles 2 through Cycle 9. Cycles 10 and beyond will receive 27 mg/m² IV on Days 1,2,15, and 16 (alternatively, the investigator could choose to continue the dosing frequency on the original dosing days \[Days 1, 2, 8, 9, 15, 16\] for individual subjects).

Treatment: Drugs: Best Supportive Care
Corticosteroid (either prednisolone 30 mg orally (PO) every other day, dexamethasone 6 mg PO every other day, or other equivalent corticosteroid).

Optional cyclophosphamide 50 mg PO once daily may be given at the Investigator's discretion (maximum of 1400 mg per 28-day cycle).
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Overall Survival
Timepoint [1] 0 0
From randomization through the final analysis data cutoff with longest follow-up time of approximately 45 months. Median follow up times were 27.8 months and 29.8 months for Carfilzomib and Best Supportive Care groups, respectively.
Secondary outcome [1] 0 0
Progression-free Survival
Timepoint [1] 0 0
From randomization through the final analysis data cutoff with longest follow-up time of approximately 31 months. Median follow up times were 26.6 months and 23.1 months for Carfilzomib and Best Supportive Care groups, respectively.
Secondary outcome [2] 0 0
Overall Response
Timepoint [2] 0 0
From randomization through the final analysis data cutoff with longest follow-up time of approximately 31 months. Median follow up times were 26.6 months and 23.1 months for Carfilzomib and Best Supportive Care groups, respectively.
Secondary outcome [3] 0 0
Duration of Response
Timepoint [3] 0 0
From the time achieving response through the final analysis data cutoff with longest follow-up time of approximately 29 months.
Secondary outcome [4] 0 0
Clinical Benefit Response
Timepoint [4] 0 0
From randomization through the final analysis data cutoff with longest follow-up time of approximately 31 months. Median follow up times were 26.6 months and 23.1 months for Carfilzomib and Best Supportive Care groups, respectively.
Secondary outcome [5] 0 0
Duration of Clinical Benefit
Timepoint [5] 0 0
From time of achieving clinical benefit through the final analysis data cutoff with longest follow-up time of approximately 30 months.
Secondary outcome [6] 0 0
Disease Control
Timepoint [6] 0 0
From randomization through the final analysis data cutoff with longest follow-up time of approximately 31 months. Median follow up times were 26.6 months and 23.1 months for Carfilzomib and Best Supportive Care groups, respectively.
Secondary outcome [7] 0 0
Duration of Disease Control
Timepoint [7] 0 0
From time of achieving disease control through the final analysis data cutoff with longest follow-up time of approximately 31 months.

Eligibility
Key inclusion criteria
1. Multiple myeloma
2. Measurable disease based on central laboratory values, as defined by one or both of the following criteria (assessed within 21 days prior to randomization):

* Serum M-protein

* Serum protein electrophoresis (SPEP): = 0.5 g/dL
* For immunoglobulin A (IgA) patients whose disease can only be reliably measured by serum quantitative immunoglobulin (qIgA): > 750 mg/dL (0.75 g/dL)
* Urine Bence Jones protein: = 200 mg/24 h
3. Responsive (defined as a 25% or greater decrease in M-protein or total protein) to at least one line of prior therapy
4. Relapsed multiple myeloma, defined as disease progression while on or after at least 1 prior treatment regimen
5. Refractory multiple myeloma, defined as meeting one or more of the following:

* Nonresponsive to most recent therapy (eg, stable disease only, or progressive disease while on treatment)
* Disease progression within 60 days of discontinuation from most recent therapy
6. Received 3 or more prior therapeutic regimens for multiple myeloma
7. Adequate prior treatment with bortezomib (if less than 4 complete cycles, the reason for discontinuation must be reviewed by the Medical Monitor and the reason documented)
8. Prior treatment with an immunomodulatory agent (lenalidomide, if available, and/or thalidomide)
9. Prior treatment with an alkylating agent (standard or high-dose)
10. Prior treatment with a corticosteroid
11. Criterion no longer applicable (with Amendment 2, Criterion 11, the requirement of "prior treatment with an anthracycline unless not clinically indicated" is removed.)
12. Age = 18 years
13. Life expectancy of at least 1 month
14. Eastern Cooperative Oncology Group (ECOG) performance status 0-2
15. Adequate hepatic function, with serum alanine aminotransferase (ALT) < 4 times the upper limit of normal and serum bilirubin < 2.5 mg/dL (42.5 µmol/L). Patients with total bilirubin = 2.5 mg/dL may enrol if their serum direct bilirubin is < 2.5 mg/dL.
16. Total white blood cell (WBC) count = 1.5 × 10^9/L and absolute neutrophil count (ANC) = 1.0 × 10^9/L (use of colony-stimulating factors to achieve these counts is allowed)
17. Hemoglobin = 7.5 g/dL (75 g/L)

-Use of erythropoietic stimulating factors is allowed:
* For all patients who receive a red blood cell (RBC) transfusion within 28 days of obtaining the Screening hemoglobin value. The following information must be provided for the Medical Monitor's review for assessment for eligibility:

* Pre-transfusion hemoglobin (Hb)
* Number of RBC units administered
* Use of erythropoietic stimulating factors
18. Platelet count = 30 × 10^9/L

-There is no restriction on platelet transfusions or thrombopoietic growth factor before or during the screening period
* For all patients who receive a platelet transfusion within 7 days of obtaining the Screening platelet value, the following information must be provided for the Medical Monitor's review for assessment of eligibility

* Pre-transfusion platelet count
* Number of platelet units administered
* Use of thrombopoietic growth factors
19. Creatinine clearance (CrCl) = 15 mL/minute (either measured or calculated using a standard formula such as Cockcroft and Gault) and dialysis-independent
20. Written informed consent in accordance with regulatory guidelines
21. Female patients of childbearing potential must have a negative serum or urine pregnancy test within 7 days of the first dose of study treatment and agree to use an effective method of contraception during the study and for 3 months following the last dose of study treatment. Post-menopausal females (> 45 years old and without menses for > 1 year) and surgically sterilized females are exempt from these requirements. Male patients must use an effective barrier method of contraception during the study and for 3 months following the last dose if sexually active with a female of childbearing potential.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Waldenström's macroglobulinemia or IgM myeloma
2. Refractory to all prior therapies
3. Disease measurable only by serum free light chain assay (SFLC)
4. POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes)
5. Plasma cell leukemia (> 2.0 × 10^9/L circulating plasma cells by standard differential)
6. Prior carfilzomib treatment
7. Chemotherapy (approved or investigational) within 14 days prior to randomization
8. Immunotherapy or antibody therapy within 28 days prior to randomization
9. Corticosteroid therapy at a dose equivalent to dexamethasone > 4 mg/day within 14 days prior to randomization
10. Radiotherapy within 7 days prior to randomization
11. Major surgery within 21 days prior to randomization
12. Congestive heart failure (NYHA Class III or IV) or symptomatic cardiac ischemia, conduction system abnormalities uncontrolled by conventional intervention (conduction abnormalities not clinically warranting intervention are allowed)
13. Myocardial infarction in the previous 3 months
14. Acute active infection requiring systemic treatment (antibiotics, antivirals, or antifungals) within 14 days prior to randomization
15. Known human immunodeficiency virus seropositivity
16. Active hepatitis A, B, or C infection
17. Other malignancy within the past 3 years with the exception of a) adequately treated basal cell carcinoma, squamous cell skin cancer, or thyroid cancer; b) carcinoma in situ of the cervix, vulva, or breast; c) prostate cancer of Gleason Score 6 or less with stable prostate-specific antigen levels; or d) cancer considered cured by surgical resection or unlikely to impact survival during the duration of the study, such as localized transitional cell carcinoma of the bladder, carcinoma in situ of the breast, or benign tumors of the adrenal or pancreas
18. Significant neuropathy (Grades 3-4, or Grade 2 with pain) at the time of randomization
19. Any other clinically significant medical disease or condition that, in the Investigator's opinion, may interfere with protocol adherence or a patient's ability to give informed consent
20. Pregnant or lactating females
21. Contraindication to any of the required concomitant drugs or supportive treatments, including hypersensitivity or known history of allergy to carfilzomib, Captisol® (a cyclodextrin derivative used to solubilize carfilzomib) all anticoagulation and antiplatelet options, antiviral drugs; or intolerance to hydration due to preexisting pulmonary or cardiac impairment

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
1/09/2010
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
1/09/2015
Sample size
Target
Accrual to date
Final
315
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
- Nedlands
Recruitment hospital [2] 0 0
- Perth
Recruitment postcode(s) [1] 0 0
- Nedlands
Recruitment postcode(s) [2] 0 0
- Perth
Recruitment outside Australia
Country [1] 0 0
Austria
State/province [1] 0 0
Linz
Country [2] 0 0
Austria
State/province [2] 0 0
Salzburg
Country [3] 0 0
Austria
State/province [3] 0 0
Vienna
Country [4] 0 0
Belgium
State/province [4] 0 0
Arlon
Country [5] 0 0
Belgium
State/province [5] 0 0
Brugge
Country [6] 0 0
Belgium
State/province [6] 0 0
Brussels
Country [7] 0 0
Belgium
State/province [7] 0 0
Roeselare
Country [8] 0 0
Czechia
State/province [8] 0 0
Brno
Country [9] 0 0
Czechia
State/province [9] 0 0
Hradec Kralov
Country [10] 0 0
Czechia
State/province [10] 0 0
Olomouc
Country [11] 0 0
Czechia
State/province [11] 0 0
Prague
Country [12] 0 0
France
State/province [12] 0 0
Lyon
Country [13] 0 0
France
State/province [13] 0 0
Nantes
Country [14] 0 0
France
State/province [14] 0 0
Nimes
Country [15] 0 0
Germany
State/province [15] 0 0
Dresden
Country [16] 0 0
Germany
State/province [16] 0 0
Giessen
Country [17] 0 0
Germany
State/province [17] 0 0
Koblenz
Country [18] 0 0
Germany
State/province [18] 0 0
Mainz
Country [19] 0 0
Germany
State/province [19] 0 0
Muenchen
Country [20] 0 0
Germany
State/province [20] 0 0
Ulm
Country [21] 0 0
Greece
State/province [21] 0 0
Athens
Country [22] 0 0
Greece
State/province [22] 0 0
Rio Patras
Country [23] 0 0
Hungary
State/province [23] 0 0
Budapest
Country [24] 0 0
Hungary
State/province [24] 0 0
Debrecen
Country [25] 0 0
Hungary
State/province [25] 0 0
Gyor
Country [26] 0 0
Hungary
State/province [26] 0 0
Gyula
Country [27] 0 0
Hungary
State/province [27] 0 0
Kaposvar
Country [28] 0 0
Hungary
State/province [28] 0 0
Pecs
Country [29] 0 0
Hungary
State/province [29] 0 0
Szeged
Country [30] 0 0
Israel
State/province [30] 0 0
Haifa
Country [31] 0 0
Israel
State/province [31] 0 0
Jerusalem
Country [32] 0 0
Israel
State/province [32] 0 0
Kfar Saba
Country [33] 0 0
Israel
State/province [33] 0 0
Nahariva
Country [34] 0 0
Israel
State/province [34] 0 0
Petah-Tikva
Country [35] 0 0
Israel
State/province [35] 0 0
Sheba
Country [36] 0 0
Italy
State/province [36] 0 0
Ancona
Country [37] 0 0
Italy
State/province [37] 0 0
Novara
Country [38] 0 0
Italy
State/province [38] 0 0
Roma
Country [39] 0 0
Italy
State/province [39] 0 0
Torino
Country [40] 0 0
Korea, Republic of
State/province [40] 0 0
Incheon
Country [41] 0 0
Korea, Republic of
State/province [41] 0 0
Seoul
Country [42] 0 0
New Zealand
State/province [42] 0 0
North Shore City
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Poland
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Gdansk
Country [44] 0 0
Poland
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Lodz
Country [45] 0 0
Poland
State/province [45] 0 0
Pila
Country [46] 0 0
Poland
State/province [46] 0 0
Torum
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Poland
State/province [47] 0 0
Warsaw
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Poland
State/province [48] 0 0
Wroclaw
Country [49] 0 0
Poland
State/province [49] 0 0
Zamosc
Country [50] 0 0
Russian Federation
State/province [50] 0 0
Moscow
Country [51] 0 0
Russian Federation
State/province [51] 0 0
St. Petersburg
Country [52] 0 0
Serbia
State/province [52] 0 0
Beograd
Country [53] 0 0
Serbia
State/province [53] 0 0
Nis
Country [54] 0 0
Slovakia
State/province [54] 0 0
Bratislava
Country [55] 0 0
Spain
State/province [55] 0 0
Barcelona
Country [56] 0 0
Spain
State/province [56] 0 0
Guipuzcoa
Country [57] 0 0
Spain
State/province [57] 0 0
Murcia
Country [58] 0 0
Spain
State/province [58] 0 0
Salamanca
Country [59] 0 0
Spain
State/province [59] 0 0
Sevilla
Country [60] 0 0
Spain
State/province [60] 0 0
Valencia
Country [61] 0 0
Spain
State/province [61] 0 0
Zaragoza
Country [62] 0 0
Sweden
State/province [62] 0 0
Uppsala
Country [63] 0 0
United Kingdom
State/province [63] 0 0
Hampshire
Country [64] 0 0
United Kingdom
State/province [64] 0 0
London
Country [65] 0 0
United Kingdom
State/province [65] 0 0
Manchester
Country [66] 0 0
United Kingdom
State/province [66] 0 0
Oxford

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

Ethics approval
Ethics application status

Summary
Brief summary
This is a Phase 3, randomized, open-label, multicenter study comparing two treatment regimens for subjects with multiple myeloma who have received all available approved treatment options and may therefore be considered candidates for palliative care.
Trial website
https://clinicaltrials.gov/study/NCT01302392
Trial related presentations / publications
Hajek R, Masszi T, Petrucci MT, Palumbo A, Rosinol L, Nagler A, Yong KL, Oriol A, Minarik J, Pour L, Dimopoulos MA, Maisnar V, Rossi D, Kasparu H, Van Droogenbroeck J, Yehuda DB, Hardan I, Jenner M, Calbecka M, David M, de la Rubia J, Drach J, Gasztonyi Z, Gornik S, Leleu X, Munder M, Offidani M, Zojer N, Rajangam K, Chang YL, San-Miguel JF, Ludwig H. A randomized phase III study of carfilzomib vs low-dose corticosteroids with optional cyclophosphamide in relapsed and refractory multiple myeloma (FOCUS). Leukemia. 2017 Jan;31(1):107-114. doi: 10.1038/leu.2016.176. Epub 2016 Jun 24.
Hajek R, Bryce R, Ro S, Klencke B, Ludwig H. Design and rationale of FOCUS (PX-171-011): a randomized, open-label, phase 3 study of carfilzomib versus best supportive care regimen in patients with relapsed and refractory multiple myeloma (R/R MM). BMC Cancer. 2012 Sep 19;12:415. doi: 10.1186/1471-2407-12-415.
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/NCT01302392