Study of Everolimus With Bevacizumab to Treat Refractory Malignant Peripheral Nerve Sheath Tumors

This study is currently recruiting participants. (see Contacts and Locations)
Verified January 2014 by Sarcoma Alliance for Research through Collaboration
Novartis Pharmaceuticals
Genentech, Inc.
Information provided by (Responsible Party):
Sarcoma Alliance for Research through Collaboration Identifier:
First received: August 7, 2012
Last updated: September 29, 2014
Last verified: January 2014

To determine the clinical response rate of everolimus in combination with bevacizumab for patients with chemotherapy refractory sporadic or neurofibromatosis type 1 (NF1) associated malignant peripheral nerve sheath tumor (MPNST). To evaluate the toxicity and safety of everolimus in combination with bevacizumab in individuals with MPNST

Condition Intervention Phase
Malignant Peripheral Nerve Sheath Tumors
Drug: everolimus
Drug: bevacizumab
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase 2 Study of the mTOR Inhibitor Everolimus in Combination With Bevacizumab in Patients With Sporadic and Neurofibromatosis Type 1 (NF1) Related Refractory Malignant Peripheral Nerve Sheath Tumors

Resource links provided by NLM:

Further study details as provided by Sarcoma Alliance for Research through Collaboration:

Primary Outcome Measures:
  • Evaluation of lesions for progression or response via Who criteria [ Time Frame: great than or equal to 4 months ] [ Designated as safety issue: No ]

Estimated Enrollment: 25
Study Start Date: September 2012
Estimated Study Completion Date: September 2016
Estimated Primary Completion Date: February 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm A
All patients with MPNST will continue everolimus 10 mg daily and bevacizumab 10 mg/kg dose every 14 days
Drug: everolimus
10 mg tablet once daily
Other Name: Afinitor, everolimus
Drug: bevacizumab
10 mg/kg dose every 14 days
Other Name: Avastin


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

Inclusion Criteria:

  • Patients 18 or older
  • Unresectable or metastatic sporadic or NF1 associated high-grade MPNST
  • Experienced progression after one or more prior regimens of cytotoxic chemotherapy
  • Patients must be able to swallow tablets
  • Patients must have measurable disease, defined as at least one tumor that is measurable
  • Patients who develop a recurrence or progression (WHO criteria) of an MPNST in a previously radiated field may be enrolled if it has been at least 4 weeks since the last dose of radiation therapy
  • Patients must have recovered from the toxic effects of all prior therapy before entering this study
  • Adequate organ function
  • ECOG performance status of 0, 1, or 2
  • Patents who received an anthracycline prior to enrollment must have an ejection fraction ≥ 50%
  • Subjects of childbearing potential requires acceptable form of birth control
  • Informed consent

Exclusion Criteria:

  • Patients currently receiving anticancer therapies or who have received anticancer therapies within 3 weeks of the start of study drug or patients receiving prior treatment with investigational drugs 4 weeks of the start of study drug
  • Patients may not be currently receiving strong inhibitors of CYP3A4, and may not have received these medications within 1 week of entry
  • Prior radiotherapy within 4 weeks of the start of study drug
  • Patients who have had a major surgery or significant traumatic injury within 4 weeks of start of study drug,
  • Patients who have not recovered from the side effects of any major surgery
  • Patients that may require major surgery during the course of the study
  • Less than 7 days have passed from core biopsies or other minor surgical procedures excluding placement of a vascular access device
  • Patients receiving chronic, systemic treatment with corticosteroids or another immunosuppressive agent(Topical or inhaled corticosteroids are allowed)
  • Uncontrolled brain or leptomeningeal metastases, including patients who continue to require glucocorticoids for brain or leptomeningeal metastases
  • Other malignancies within the past 3 years except for adequately treated carcinoma of the cervix or basal or squamous cell carcinomas of the skin
  • Patients who have any severe and/or uncontrolled medical conditions or other conditions that could affect their participation in the study
  • Female patients who are pregnant or breast feeding
  • Patients who have received prior treatment with an mTOR inhibitor or bevacizumab
  • Patients with known hypersensitivity to rapamycins
  • concurrent use of anti-coagulant drugs
  • Patients using Seville orange, star fruit, grapefruit and their juices, and St. John's Wort
  • Patients taking enzyme inducing anticonvulsants
  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 identifier: NCT01661283

Contact: Denise Reinke, MS, NP 734-930-7600

United States, Alabama
University of Alabama at Birmingham Recruiting
Birmingham, Alabama, United States, 35294-0024
Contact: Julia Adams    205-638-2984   
Principal Investigator: Joseph Pressey, MD         
United States, District of Columbia
Children's National Medical Center Recruiting
Washington D.C., District of Columbia, United States, 20010
Contact: Alissa Mun    202-476-5546   
Principal Investigator: AeRang Kim, MD         
United States, Illinois
Ann and Robert Lurie Children's Hospital of Chicago Recruiting
Chicago, Illinois, United States, 60611
Contact: Jillian Tabares    312-227-4810   
Principal Investigator: Stewart Goldman, M.D.         
United States, Iowa
University of Iowa Recruiting
Iowa City, Iowa, United States, 52242
Contact: Leslie Brautigam    319-467-5831   
Principal Investigator: Mohammed Milhem, MD         
United States, Maryland
Johns Hopkins Recruiting
Baltimore, Maryland, United States, 21218
Contact: Margaret Fogle, MS, RN    410-955-7349   
Principal Investigator: Christian Meyer, MD         
Sub-Investigator: Katherine Thornton, MD         
National Cancer Institute Recruiting
Bethesda, Maryland, United States, 20892-1101
Contact: Lauren Long    301-496-0486   
Principal Investigator: Brigitte C. Widemann, MD         
United States, Massachusetts
Massachusetts General Hospital Recruiting
Boston, Massachusetts, United States, 02114
Contact: Kristina Reardon    617-643-6256   
Principal Investigator: Greg Cote, MD, PhD         
United States, Michigan
University of Michigan Recruiting
Ann Arbor, Michigan, United States, 48109
Contact: Gino Metko    734-936-0453   
Principal Investigator: Scott Schuetze, MD         
United States, Missouri
Washington University in St. Louis Recruiting
St. Louis, Missouri, United States, 63130
Contact: Kristina Williams    314-362-6963   
Principal Investigator: Brian Van Tine, MD         
United States, Ohio
Cincinnati Children's Hospital Medical Center Recruiting
Cincinnati, Ohio, United States, 45229-3039
Contact: Laurie Grimme, CCRP    513-636-8616   
Principal Investigator: Brian Turpin, MD         
United States, Pennsylvania
Children's Hospital of Philadelphia Not yet recruiting
Philadelphia, Pennsylvania, United States, 19104
Principal Investigator: Michael Fisher, MD         
Pennsylvania Oncology Hematology Associates Active, not recruiting
Philadelphia, Pennsylvania, United States, 19106
Sponsors and Collaborators
Sarcoma Alliance for Research through Collaboration
Novartis Pharmaceuticals
Genentech, Inc.
Principal Investigator: Brigitte C. Widemann, MD National Cancer Institute (NCI)
  More Information

Additional Information:
No publications provided

Responsible Party: Sarcoma Alliance for Research through Collaboration Identifier: NCT01661283     History of Changes
Other Study ID Numbers: SARC016
Study First Received: August 7, 2012
Last Updated: September 29, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Sarcoma Alliance for Research through Collaboration:
malignant peripheral nerve sheath tumors
mTOR inhibitor

Additional relevant MeSH terms:
Nerve Sheath Neoplasms
Neoplasms by Histologic Type
Neoplasms, Connective Tissue
Neoplasms, Connective and Soft Tissue
Neoplasms, Fibrous Tissue
Neoplasms, Germ Cell and Embryonal
Neoplasms, Nerve Tissue
Nervous System Diseases
Nervous System Neoplasms
Neuroectodermal Tumors
Neuroendocrine Tumors
Neuromuscular Diseases
Peripheral Nervous System Diseases
Peripheral Nervous System Neoplasms
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Anti-Bacterial Agents
Anti-Infective Agents
Antibiotics, Antineoplastic
Antifungal Agents processed this record on March 31, 2015