Full Text View  
  Tabular View  
  Contacts and Locations  
  No Study Results Posted  
  Related Studies  
Sorafenib and Everolimus in Treating Patients With Relapsed or Refractory Lymphoma or Multiple Myeloma
This study is currently recruiting participants.
Verified by National Cancer Institute (NCI), January 2009
Sponsors and Collaborators: Mayo Clinic
National Cancer Institute (NCI)
Information provided by: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00474929
  Purpose

RATIONALE: Sorafenib and everolimus may stop the growth of cancer cells by blocking blood flow to the cancer and by blocking some of the enzymes needed for cell growth.

PURPOSE: This phase I/II trial is studying the side effects and best dose of sorafenib and everolimus and to see how well they work in treating patients with relapsed or refractory non-Hodgkin's lymphoma, Hodgkin's lymphoma, or multiple myeloma.


Condition Intervention Phase
Lymphoma
Multiple Myeloma and Plasma Cell Neoplasm
Drug: everolimus
Drug: sorafenib tosylate
Procedure: flow cytometry
Procedure: immunoenzyme technique
Procedure: immunohistochemistry staining method
Procedure: pharmacological study
Phase I
Phase II

Genetics Home Reference related topics: aceruloplasminemia hemophilia
MedlinePlus related topics: Cancer Hodgkin's Disease Lymphoma Multiple Myeloma
Drug Information available for: Sorafenib Sorafenib tosylate Everolimus
U.S. FDA Resources
Study Type: Interventional
Study Design: Treatment
Official Title: A Phase I/II Study of the Raf Kinase/VEGFR Inhibitor Sorafenib in Combination With the mTOR Inhibitor RAD001 (Everolimus) in Patients With Relapsed Non-Hodgkin Lymphoma, Hodgkin Lymphoma, or Multiple Myeloma

Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Toxicity profile as assessed by NCI CTCAE v 3.0 (Phase I) [ Designated as safety issue: Yes ]
  • Adverse events profile (Phase I) [ Designated as safety issue: Yes ]
  • Proportion of confirmed tumor response (Phase II) [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Survival time (Phase II) [ Designated as safety issue: No ]
  • Time to disease progression (Phase II) [ Designated as safety issue: No ]

Estimated Enrollment: 103
Study Start Date: August 2007
Estimated Primary Completion Date: December 2011 (Final data collection date for primary outcome measure)
Detailed Description:

OBJECTIVES:

  • Determine the maximum tolerated dose (MTD) of sorafenib tosylate and everolimus in patients with relapsed or refractory non-Hodgkin's lymphoma, Hodgkin's lymphoma, or multiple myeloma.
  • Determine the toxicity of this regimen in this patients.
  • Evaluate the therapeutic activity of this regimen in these patients.
  • Evaluate the pharmacokinetic interaction of this regimen.
  • Correlate clinical (toxicity and/or tumor response or activity) effects with pharmacologic (pharmacokinetic/pharmacodynamic) parameters and/or biologic (correlative laboratory) results.

OUTLINE: This is a multicenter, dose-escalation, phase I study followed by a phase II study.

  • Phase I: Patients receive oral sorafenib tosylate and oral everolimus on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of sorafenib tosylate and everolimus until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 1 of 3 or 2 of 6 patients experience dose-limiting toxicity.

  • Phase II: Patients receive oral sorafenib tosylate and oral everolimus at the MTD determined in phase I. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Blood and bone marrow are collected periodically during the study and analyzed by flow cytometry, immunohistochemistry, and enzyme-linked immunosorbent assay. Patients enrolled in phase I also undergo blood sample collection on days 8 and 15 during course 1 and on day 1 of each subsequent course for pharmacokinetic studies.

After completion of study treatment, patients are followed every 6 months for 3 years.

PROJECTED ACCRUAL: A total of 103 patients will be accrued for this study.

  Eligibility

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

DISEASE CHARACTERISTICS:

  • Histologically or cytologically confirmed diagnosis of 1 of the following:

    • Multiple myeloma
    • Non-Hodgkin's lymphoma
    • Hodgkin's lymphoma
  • Relapsed or refractory disease
  • Measurable disease, as defined according to diagnosis as follows:

    • Multiple myeloma, meeting 1 of the following criteria:

      • Serum monoclonal protein ≥ 1.0 g by protein electrophoresis
      • Urine monoclonal protein ≥ 200 mg by 24-hour electrophoresis
      • Serum immunoglobulin free light chain ≥ 10 mg/dL AND abnormal serum immunoglobulin kappa to lambda free light chain ratio
      • Monoclonal bone marrow plasmacytosis ≥ 30% (evaluable disease)
    • Lymphoma, meeting 1 of the following criteria:

      • Measurable disease by CT scan or MRI or PET/CT scan, defined as ≥ 1 lesion that has a single diameter of ≥ 2 cm OR tumor cells in the blood ≥ 5 x10^9/L

        • Skin lesions can be used if the area is ≥ 2 cm in ≥ 1 diameter and photographed with a ruler
    • Lymphoplasmacytic lymphoma without measurable lymphadenopathy, meeting both of the following criteria:

      • Bone marrow lymphoplasmacytosis with > 10% lymphoplasmacytic cells or aggregates, sheets, lymphocytes, plasma cells, or lymphoplasmacytic cells on bone marrow biopsy
      • Quantitative IgM monoclonal protein > 1,000 mg/dL
  • Not a candidate for known standard potentially curative therapy

PATIENT CHARACTERISTICS:

  • ECOG performance status 0-2
  • Life expectancy ≥ 12 weeks
  • ANC ≥ 1,500/mm³
  • Hemoglobin ≥ 9 g/dL
  • Platelet count ≥ 75,000/mm³
  • Bilirubin ≤ 1.5 times upper limit of normal (ULN) OR direct bilirubin normal
  • AST ≤ 3 times ULN (5 times ULN if liver involvement)
  • Creatinine ≤ 2.5 times ULN
  • INR < 1.5 or activated PTT < 1.5 times ULN (no concurrent anticoagulants)
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective barrier contraception during and for at least 2 weeks after completion of study treatment
  • No uncontrolled infection
  • No NYHA class III-IV congestive heart failure
  • No unstable angina (anginal symptoms at rest) or new onset angina (began within the last 3 months)
  • No myocardial infarction within the past 6 months
  • No uncontrolled hypertension, defined as systolic blood pressure (BP) > 150 mm Hg or diastolic BP > 90 mm Hg, despite optimal medical management
  • No known HIV positivity
  • No other active malignancy requiring treatment
  • No inability to swallow
  • No gastrointestinal (GI) function impairment or GI disease that may significantly alter the absorption of the study drugs (e.g., ulcerative disease, uncontrolled nausea, vomiting, or diarrhea, malabsorption syndrome, or small bowel resection) or preclude use of oral medications
  • No thrombolic or embolic events (e.g., cerebrovascular accident, including transient ischemic attacks) within the past 6 months
  • No pulmonary hemorrhage or bleeding event ≥ grade 3 within the past 4 weeks
  • No severe or uncontrolled medical conditions or other conditions that would preclude study compliance
  • No liver disease, such as cirrhosis, chronic hepatitis or chronic persistent hepatitis, or uncontrolled infections
  • No serious nonhealing wound, ulcer, or bone fracture
  • No evidence or history of serious bleeding diathesis or coagulopathy, such as hemophilia or von Willebrand's disease
  • No significant traumatic injury within the past 4 weeks
  • No known hypersensitivity to everolimus or other rapamycins (sirolimus, temsirolimus)

PRIOR CONCURRENT THERAPY:

  • More than 3 weeks since prior myelosuppressive chemotherapy or biological therapy and recovered
  • More than 4 weeks since prior major surgery or open biopsy

    • Lymph node biopsy within past 4 weeks allowed
  • Prior everolimus allowed
  • No concurrent immunosuppressant therapy

    • Concurrent stable chronic doses of steroids (≤ 20 mg of prednisone per day) for disorders other than lymphoma (i.e., rheumatoid arthritis, polymyalgia rheumatica, adrenal insufficiency, asthma) or for pruritus or fever associated with lymphoma allowed
    • Concurrent corticosteroids at the lowest possible dose necessary to control symptoms in patients with CNS lymphoma allowed
  • No concurrent CYP450 enzyme-inducing antiepileptic drugs (e.g., phenytoin, carbamazepine, or phenobarbital), rifampin, or Hypericum perforatum (St. John's wort)
  • No other concurrent immunotherapy, radiotherapy, or chemotherapy
  • No concurrent chronic oxygen therapy
  • No concurrent warfarin or heparin
  • No other concurrent investigational therapy
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00474929

Locations
United States, Iowa
Holden Comprehensive Cancer Center at University of Iowa Recruiting
Iowa City, Iowa, United States, 52242-1002
Contact: Cancer Information Service     800-237-1225        
United States, Minnesota
Mayo Clinic Cancer Center Recruiting
Rochester, Minnesota, United States, 55905
Contact: Clinical Trials Office - All Mayo Clinic Locations     507-538-7623        
Sponsors and Collaborators
Mayo Clinic
Investigators
Principal Investigator: Thomas E. Witzig, MD Mayo Clinic
Principal Investigator: Shaji K. Kumar, MD Mayo Clinic
  More Information

Clinical trial summary from the National Cancer Institute's PDQ® database  This link exits the ClinicalTrials.gov site

Study ID Numbers: CDR0000544786, MAYO-LS0689, MAYO-07-000710
Study First Received: May 16, 2007
Last Updated: January 7, 2009
ClinicalTrials.gov Identifier: NCT00474929  
Health Authority: Unspecified

Keywords provided by National Cancer Institute (NCI):
recurrent adult Hodgkin lymphoma
recurrent cutaneous T-cell non-Hodgkin lymphoma
stage III multiple myeloma
refractory multiple myeloma
Waldenstrom macroglobulinemia
recurrent adult Burkitt lymphoma
recurrent adult diffuse large cell lymphoma
recurrent adult diffuse mixed cell lymphoma
recurrent adult diffuse small cleaved cell lymphoma
recurrent adult immunoblastic large cell lymphoma
recurrent adult lymphoblastic lymphoma
recurrent grade 1 follicular lymphoma
recurrent grade 2 follicular lymphoma
recurrent grade 3 follicular lymphoma
recurrent mantle cell lymphoma
recurrent marginal zone lymphoma
recurrent small lymphocytic lymphoma
cutaneous B-cell non-Hodgkin lymphoma
extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue
nodal marginal zone B-cell lymphoma
splenic marginal zone lymphoma
recurrent mycosis fungoides/Sezary syndrome
recurrent adult grade III lymphomatoid granulomatosis

Study placed in the following topic categories:
Sezary syndrome
Lymphoma, Mantle-Cell
Hodgkin lymphoma, adult
Lymphoma, small cleaved-cell, diffuse
Lymphoma, large-cell, immunoblastic
Mycoses
Lymphomatoid granulomatosis
Hemorrhagic Disorders
Multiple myeloma
Leukemia, Lymphocytic, Chronic, B-Cell
Hodgkin Disease
Chronic lymphocytic leukemia
Lymphoma, Large B-Cell, Diffuse
Immunoproliferative Disorders
Hematologic Diseases
Blood Coagulation Disorders
Leukemia, B-cell, chronic
Multiple Myeloma
Waldenstrom Macroglobulinemia
B-cell lymphomas
Lymphoma, Non-Hodgkin
Lymphoma, T-Cell, Cutaneous
Hodgkin's disease
Blood Protein Disorders
Cutaneous T-cell lymphoma
Lymphoma, Follicular
Lymphoma, B-Cell, Marginal Zone
Sezary Syndrome
Paraproteinemias
Mycosis Fungoides

Additional relevant MeSH terms:
Neoplasms by Histologic Type
Immune System Diseases
Immunologic Factors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Physiological Effects of Drugs
Enzyme Inhibitors
Immunosuppressive Agents
Protein Kinase Inhibitors
Pharmacologic Actions
Neoplasms
Therapeutic Uses
Cardiovascular Diseases

ClinicalTrials.gov processed this record on January 16, 2009