A Study of Carfilzomib vs Best Supportive Care in Subjects With Relapsed and Refractory Multiple Myeloma (FOCUS)

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Onyx Pharmaceuticals ( Onyx Therapeutics, Inc. )
ClinicalTrials.gov Identifier:
NCT01302392
First received: February 10, 2011
Last updated: December 4, 2013
Last verified: December 2013

February 10, 2011
December 4, 2013
September 2010
June 2014   (final data collection date for primary outcome measure)
Overall Survival [ Time Frame: Up to 3 years ] [ Designated as safety issue: No ]
The primary objective of this study is to compare overall survival (OS) in patients with refractory multiple myeloma relapsed after at least 3 prior regimens who are randomized to receive either carfilzomib (Regimen C) or best supportive care (Regimen BSC).
Progression Free Survival [ Time Frame: 12 months ] [ Designated as safety issue: No ]
Disease-related assessments will be performed on Day 1 and Day 15 of Cycle 1 through Cycle 9, and on Day 1 for Cycle 10 and beyond through an anticipated period of 12 months.
Complete list of historical versions of study NCT01302392 on ClinicalTrials.gov Archive Site
Progression Free Survival [ Time Frame: 1 year ] [ Designated as safety issue: No ]

The secondary objectives of this study include investigating the effect of carfilzomib on other standard efficacy variables including PFS, overall response rate (ORR), disease control rate (DCR), and duration of response.

Additionally, this study will examine the safety profile of carfilzomib alone compared with best supportive care based on the incidence and severity of adverse events (AEs) and laboratory changes.

Overall Survival [ Time Frame: 12 months ] [ Designated as safety issue: No ]
Post-treatmen follow-up for disease status and survival will proceed for up to 3 years
Not Provided
Not Provided
 
A Study of Carfilzomib vs Best Supportive Care in Subjects With Relapsed and Refractory Multiple Myeloma
A Randomized, Open-label, Phase 3 Study of Carfilzomib vs Best Supportive Care in Subjects With Relapsed and Refractory Multiple Myeloma

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 would otherwise be offered palliative care. These subjects must have received at least 3 prior treatments for their disease and be refractory to their most recent therapy.

Not Provided
Interventional
Phase 3
Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Multiple Myeloma
  • Drug: 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.
    Other Name: PR-171
  • Drug: 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).

  • Active Comparator: Best Supportive Care
    Intervention: Drug: Best Supportive Care
  • Experimental: carfilzomib
    Intervention: Drug: carfilzomib
Hájek 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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Active, not recruiting
302
January 2015
June 2014   (final data collection date for primary outcome measure)

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 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 × 109/L and absolute neutrophil count (ANC) ≥ 1.0 × 109/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 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 Hb
    • Number of RBC units administered
    • Use of erythropoietic stimulating factors
  18. Platelet count ≥ 30 × 109/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.

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 × 109/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
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
Australia,   Austria,   Belgium,   Czech Republic,   France,   Germany,   Greece,   Hungary,   Israel,   Italy,   Korea, Republic of,   New Zealand,   Poland,   Russian Federation,   Serbia,   Slovakia,   Spain,   Sweden,   United Kingdom
 
NCT01302392
PX-171-011
Yes
Onyx Pharmaceuticals ( Onyx Therapeutics, Inc. )
Onyx Therapeutics, Inc.
Not Provided
Principal Investigator: Roman Hajek, MD University Hospital, Brno, Czech Republic
Principal Investigator: Heinz Ludwig, MD Center for Oncology and Haematology, Vienna, Austria
Onyx Pharmaceuticals
December 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP