Phase 3 Study With Carfilzomib and Dexamethasone Versus Velcade 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: June 27, 2014
Last verified: June 2014

March 28, 2012
June 27, 2014
June 2012
January 2016   (final data collection date for primary outcome measure)
Progression Free Survival [ Time Frame: 30 months ] [ Designated as safety issue: No ]
To compare Progression Free Survival (PFS) in patients with multiple myeloma relapsed after 1 to 3 prior therapies treated with carfilzomib or velcade.
Progression Free Survival [ Time Frame: 30 months ] [ Designated as safety issue: No ]
To compare Progression Free Survival(PFS) in patients with multiple myeloma relapsed after 1 to 3 prior therapies treated with carfilzomib or velcade.
Complete list of historical versions of study NCT01568866 on ClinicalTrials.gov Archive Site
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Phase 3 Study With Carfilzomib and Dexamethasone Versus Velcade and Dexamethasone for Relapsed Multiple Myeloma Patients
A Randomized, Open-label, Phase 3 Study of Carfilzomib Plus Dexamethasone vs. Bortezomib Plus Dexamethasone in Patients With Relapsed Multiple Myeloma

This Phase 3 study is a multicenter, open-label, randomized trial in patients with multiple myeloma whose disease has relapsed after at least 1 but not more than 3 prior therapeutic regimens. Patients must not have primary refractory disease (i.e., stable disease or progressive disease [PD] as best response to all prior therapies). Patients are allowed to have received prior carfilzomib or Velcade as long as they had at least a PR to prior therapy with carfilzomib or Velcade and at least a 6 month treatment-free interval since receiving carfilzomib or Velcade. Patients may receive maintenance therapy with drugs that are not in the proteasome inhibitor class during this 6 month treatment-free interval.

Not Provided
Interventional
Phase 3
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Multiple Myeloma
  • Drug: Carfilzomib plus dexamethasone
    Carfilzomib is administered over 30 minutes (± 5 minutes) as an infusion. For Cycle 1 only, carfilzomib is administered at 20 mg/m2 IV on Days 1 and 2, followed by escalation to 56 mg/m2 on Days 8, 9, 15, and 16. Patients who tolerate 56 mg/m2 in Cycle 1 are kept at this dose on Days 1, 2, 8, 9, 15, and 16 on a 28 day cycle. Dose and schedule modifications for intolerable side effects to carfilzomib are detailed in the protocol. Additionally, dexamethasone is administered on Days 1, 2, 8, 9, 15, 16, 22, and 23 of a 28 day cycle. On days when carfilzomib is administered, dexamethasone is to be given 30 minutes to 4 hours prior to carfilzomib.
    Other Names:
    • PR-171
    • carfilzomib
    • Carfilzomib
  • Drug: Velcade plus dexamethasone
    Velcade 1.3 mg/m2 is administered as a 3-5 second bolus IV injection or SC injection (in accordance with regulatory approval) on Days 1, 4, 8, and 11 of each 21-day cycle until PD or intolerable side effects. Dose and schedule modifications for intolerable side effects to Velcade are detailed in the protocol. Additionally, dexamethasone 20 mg is given on Days 1, 2, 4, 5, 8, 9, 11, and 12 of each 21 day cycle. On days when Velcade is administered, the dexamethasone is to be given 30 minutes to 4 hours prior to Velcade.
    Other Names:
    • Velcade
    • Bortezomib
    • bortezomib
    • Vd
    • vd
  • Experimental: Carfilzomib plus Dexamethasone (Cd)
    Carfilzomib is administered over 30 minutes (± 5 minutes) as an infusion. For Cycle 1 only, carfilzomib is administered at 20 mg/m2 IV on Days 1 and 2, followed by escalation to 56 mg/m2 on Days 8, 9, 15, and 16. Patients who tolerate 56 mg/m2 in Cycle 1 are kept at this dose on Days 1, 2, 8, 9, 15, and 16 on a 28 day cycle. Dose and schedule modifications for intolerable side effects to carfilzomib are detailed in the protocol. Additionally, dexamethasone is administered on Days 1, 2, 8, 9, 15, 16, 22, and 23 of a 28 day cycle. On days when carfilzomib is administered, dexamethasone is to be given 30 minutes to 4 hours prior to carfilzomib.
    Intervention: Drug: Carfilzomib plus dexamethasone
  • Active Comparator: Bortezomib (Velcade®) and Dexamethasone (Vd)
    Velcade 1.3 mg/m2 administered IV or subcutaneously (SC) (route of administration of Velcade in accordance with regulatory approval) administered 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 a 21-day cycle. Patients should be encouraged to continue to receive Velcade by the same route of administration (SC or IV) throughout treatment (i.e., a patient should not begin receiving IV and then switch to SC, or vice versa).
    Intervention: Drug: Velcade plus dexamethasone
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Active, not recruiting
898
March 2019
January 2016   (final data collection date for primary outcome measure)

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 IgA 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 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. 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.

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 × 109/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 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.
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United States,   Australia,   Austria,   Belgium,   Brazil,   Bulgaria,   Canada,   Czech Republic,   France,   Germany,   Greece,   Hungary,   Israel,   Italy,   Japan,   Korea, Republic of,   New Zealand,   Poland,   Romania,   Russian Federation,   Singapore,   Slovakia,   Spain,   Taiwan,   Thailand,   Ukraine,   United Kingdom
 
NCT01568866
2011-003, 2012-000128-16
Yes
Onyx Pharmaceuticals
Onyx Pharmaceuticals
Not Provided
Principal Investigator: Hartmut Goldschmidt, MD Universitätsklinik Heidelberg, Heidelberg, Germany
Principal Investigator: Douglas Joshua, BSc, MBBS, DPhil (Oxon), FRACP Royal Prince Alfred Hospital, Camperdown, Australia
Principal Investigator: Philippe Moreau, MD Hôpital Hôtel-Dieu, NANTES Cedex 01, France
Principal Investigator: Robert Orlowski, PhD, MD UT M.D. Anderson Cancer Center, MD Anderson Cancer Center, Houston, Texas
Onyx Pharmaceuticals
June 2014

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