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

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborators:
Novartis Pharmaceuticals
Genentech
Information provided by (Responsible Party):
Sarcoma Alliance for Research through Collaboration
ClinicalTrials.gov Identifier:
NCT01661283
First received: August 7, 2012
Last updated: January 16, 2014
Last verified: January 2014
  Purpose

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
MPNST
Sarcoma
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

  Eligibility

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

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 ClinicalTrials.gov identifier: NCT01661283

Locations
United States, Alabama
University of Alabama at Birmingham
Birmingham, Alabama, United States, 35294-0024
United States, District of Columbia
Children's National Medical Center
Washington D.C., District of Columbia, United States, 20010
United States, Illinois
Ann and Robert Lurie Children's Hospital of Chicago
Chicago, Illinois, United States, 60611
United States, Iowa
University of Iowa
Iowa City, Iowa, United States, 52242
United States, Maryland
Johns Hopkins
Baltimore, Maryland, United States, 21218
National Cancer Institute
Bethesda, Maryland, United States, 20892-1101
United States, Massachusetts
Massachusetts General Hospital
Boston, Massachusetts, United States, 02114
United States, Michigan
University of Michigan
Ann Arbor, Michigan, United States, 48109
United States, Missouri
Washington University in St. Louis
St. Louis, Missouri, United States, 63130
United States, Ohio
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, United States, 45229-3039
United States, Pennsylvania
Pennsylvania Oncology Hematology Associates
Philadelphia, Pennsylvania, United States, 19106
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, United States, 19104
Sponsors and Collaborators
Sarcoma Alliance for Research through Collaboration
Novartis Pharmaceuticals
Genentech
Investigators
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
ClinicalTrials.gov Identifier: NCT01661283     History of Changes
Other Study ID Numbers: SARC016
Study First Received: August 7, 2012
Last Updated: January 16, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Sarcoma Alliance for Research through Collaboration:
MPNST
malignant peripheral nerve sheath tumors
RAD001
Everolimus
Bevacizumab
Sarcoma
Avastin
mTOR inhibitor

Additional relevant MeSH terms:
Neurofibromatosis 1
Neurofibromatoses
Nerve Sheath Neoplasms
Neurofibrosarcoma
Neurilemmoma
Sarcoma
Neurofibroma
Neoplasms, Nerve Tissue
Neoplasms by Histologic Type
Neoplasms
Neoplastic Syndromes, Hereditary
Neurocutaneous Syndromes
Nervous System Diseases
Heredodegenerative Disorders, Nervous System
Neurodegenerative Diseases
Peripheral Nervous System Diseases
Neuromuscular Diseases
Genetic Diseases, Inborn
Peripheral Nervous System Neoplasms
Nervous System Neoplasms
Fibrosarcoma
Neoplasms, Fibrous Tissue
Neoplasms, Connective Tissue
Neoplasms, Connective and Soft Tissue
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neuroma
Everolimus
Sirolimus

ClinicalTrials.gov processed this record on July 26, 2014