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
  Purpose

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.


Condition Intervention Phase
Multiple Myeloma
Drug: carfilzomib
Drug: Best Supportive Care
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Randomized, Open-label, Phase 3 Study of Carfilzomib vs Best Supportive Care in Subjects With Relapsed and Refractory Multiple Myeloma

Resource links provided by NLM:


Further study details as provided by Onyx Pharmaceuticals:

Primary Outcome Measures:
  • 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).


Secondary Outcome Measures:
  • 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.



Estimated Enrollment: 302
Study Start Date: September 2010
Estimated Study Completion Date: January 2015
Estimated Primary Completion Date: June 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Best Supportive Care 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).

Experimental: carfilzomib 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

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01302392

  Hide Study Locations
Locations
Australia
Nedlands, Australia
Perth, Australia
Austria
Linz, Austria
Salzburg, Austria
Vienna, Austria
Belgium
Arlon, Belgium
Brugge, Belgium
Brussels, Belgium
Roeselare, Belgium
Czech Republic
Brno, Czech Republic
Hradec Kralov, Czech Republic
Olomouc, Czech Republic
Prague, Czech Republic
France
Lyon, France
Nantes, France
Nimes, France
Germany
Dresden, Germany
Giessen, Germany
Koblenz, Germany
Mainz, Germany
Muenchen, Germany
Ulm, Germany
Greece
Athens, Greece
Rio Patras, Greece
Hungary
Budapest, Hungary
Debrecen, Hungary
Gyor, Hungary
Gyula, Hungary
Kaposvar, Hungary
Pecs, Hungary
Szeged, Hungary
Israel
Haifa, Israel
Jerusalem, Israel
Kfar Saba, Israel
Nahariva, Israel
Petah-Tikva, Israel
Sheba, Israel
Italy
Ancona, Italy
Novara, Italy
Roma, Italy
Torino, Italy
Korea, Republic of
Incheon, Korea, Republic of
Seoul, Korea, Republic of
New Zealand
North Shore City, New Zealand
Poland
Gdansk, Poland
Lodz, Poland
Pila, Poland
Torum, Poland
Warsaw, Poland
Wroclaw, Poland
Zamosc, Poland
Russian Federation
Moscow, Russian Federation
St. Petersburg, Russian Federation
Serbia
Beograd, Serbia
Nis, Serbia
Slovakia
Bratislava, Slovakia
Spain
Barcelona, Spain
Guipuzcoa, Spain
Murcia, Spain
Salamanca, Spain
Sevilla, Spain
Valencia, Spain
Zaragoza, Spain
Sweden
Uppsala, Sweden
United Kingdom
Hampshire, United Kingdom
London, United Kingdom
Manchester, United Kingdom
Oxford, United Kingdom
Sponsors and Collaborators
Onyx Therapeutics, Inc.
Investigators
Principal Investigator: Roman Hajek, MD University Hospital, Brno, Czech Republic
Principal Investigator: Heinz Ludwig, MD Center for Oncology and Haematology, Vienna, Austria
  More Information

No publications provided by Onyx Pharmaceuticals

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Onyx Pharmaceuticals ( Onyx Therapeutics, Inc. )
ClinicalTrials.gov Identifier: NCT01302392     History of Changes
Other Study ID Numbers: PX-171-011
Study First Received: February 10, 2011
Last Updated: December 4, 2013
Health Authority: Austria: Federal Office for Safety in Health Care
Austria: Agency for Health and Food Safety
Austria: Austrian Medicines and Medical Devices Agency
Austria: Ethikkommission
Australia: Department of Health and Ageing Therapeutic Goods Administration
Australia: Human Research Ethics Committee
Belgium: Federal Agency for Medicinal Products and Health Products
Belgium: Federal Agency for Medicines and Health Products, FAMHP
Belgium: Ethics Committee
Belgium: Institutional Review Board
Belgium: Ministry of Social Affairs, Public Health and the Environment
Belgium: The Federal Public Service (FPS) Health, Food Chain Safety and Environment
Czech Republic: State Institute for Drug Control
Czech Republic: Ethics Committee
France: The Commission nationale de l’informatique et des libertés
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
France: Institutional Ethical Committee
France: Ministry of Health
France: Ministère de l'Enseignement supérieur et de la Recherche
France: National Consultative Ethics Committee for Health and Life Sciences
Germany: Federal Institute for Drugs and Medical Devices
Germany: Ethics Commission
Greece: National Organization of Medicines
Greece: Ethics Committee
Hungary: National Institute of Pharmacy
Hungary: Institutional Ethics Committee
Israel: Ministry of Health
Israel: Ethics Commission
Italy: The Italian Medicines Agency
Italy: Ethics Committee
Poland: Ministry of Health
Poland: Ethics Committee
Russia: Ministry of Health of the Russian Federation
Russia: Ethics Committee
Serbia and Montenegro: Agency for Drugs and Medicinal Devices
Serbia: Ethics Committee
Slovakia: State Institute for Drug Control
Slovak Republic: Ethics Committee
South Korea: Korea Food and Drug Administration (KFDA)
South Korea: Institutional Review Board
Spain: Agencia Española de Medicamentos y Productos Sanitarios
Spain: Ethics Committee
Sweden: Medical Products Agency
Sweden: Institutional Review Board
United Kingdom: Medicines and Healthcare Products Regulatory Agency
United Kingdom: National Health Service
United Kingdom: National Institute for Health Research
United Kingdom: Research Ethics Committee

Additional relevant MeSH terms:
Multiple Myeloma
Neoplasms, Plasma Cell
Blood Protein Disorders
Cardiovascular Diseases
Hematologic Diseases
Hemorrhagic Disorders
Hemostatic Disorders
Immune System Diseases
Immunoproliferative Disorders
Lymphoproliferative Disorders
Neoplasms
Neoplasms by Histologic Type
Paraproteinemias
Vascular Diseases

ClinicalTrials.gov processed this record on October 23, 2014