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Trial record 16 of 20 for:    "Neurofibromatosis, Type I" | "Anti-Infective Agents"

SARC016: Study of Everolimus With Bevacizumab to Treat Refractory Malignant Peripheral Nerve Sheath Tumors

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ClinicalTrials.gov Identifier: NCT01661283
Recruitment Status : Completed
First Posted : August 9, 2012
Results First Posted : March 6, 2019
Last Update Posted : March 6, 2019
Sponsor:
Collaborators:
Novartis Pharmaceuticals
Genentech, Inc.
United States Department of Defense
Information provided by (Responsible Party):
Sarcoma Alliance for Research through Collaboration

Brief Summary:
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 or disease Intervention/treatment Phase
Malignant Peripheral Nerve Sheath Tumors MPNST Sarcoma Drug: everolimus Drug: bevacizumab Phase 2

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 25 participants
Intervention Model: Single Group Assignment
Masking: None (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
Study Start Date : September 2012
Actual Primary Completion Date : June 2017
Actual Study Completion Date : December 2017


Arm Intervention/treatment
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




Primary Outcome Measures :
  1. Clinical Benefit Rate (Complete Response, Partial Response, and Stable Disease at ≥ 4 Months Using World Health Organization (WHO) Criteria) of Everolimus in Combination With Bevacizumab [ Time Frame: Assessed at Baseline and prior to Cycle 3, 5, 7, 9, etc., for up to 2 years. 1 cycle =28 days ]

    Evaluate if the combination of the mTOR inhibitor everolimus combined with the angiogenesis inhibitor bevacizumab would result in a modest clinical benefit rate, which included confirmed partial and complete responses and disease stability for four or more treatment cycles based on WHO Response Criteria. Per WHO for target lesions: Complete Response (CR): Disappearance of all known disease, determined by two consecutive observations not less than 4 weeks apart.

    Partial Response (PR): A > 50% decrease in the total tumor load of the lesions that have been measured to determine the effect of therapy not less than four weeks apart. The observations must be consecutive. Stable Disease (SD): A 50% decrease in total tumor area cannot be established nor has a 25% increase in the size of one or more measurable lesions been demonstrated.



Secondary Outcome Measures :
  1. Spectrum of Germline NF1 Mutations in Individuals With NF1 Associated MPNSTs [ Time Frame: greater than or equal to 4 months ]
    To evaluate the spectrum of germline NF1 mutations in individuals with NF1 associated MPNSTs

  2. Number of Participants With Response Stratified by Individuals With Sporadic or NF1 Associated MPNST [ Time Frame: Assessed at Baseline and prior to Cycle 3, 5, 7, 9, etc., for up to 2 years. 1 cycle =28 days ]
    To explore differences in the response rate to everolimus in combination with bevacizumab in individuals with sporadic and NF1 associated MPNST. Responses include confirmed partial and complete responses and disease stability for four or more treatment cycles based on WHO Response Criteria. Per WHO for target lesions: Complete Response (CR): Disappearance of all known disease, determined by two consecutive observations not less than 4 weeks apart. Partial Response (PR): A > 50% decrease in the total tumor load of the lesions that have been measured to determine the effect of therapy not less than four weeks apart. The observations must be consecutive. Stable Disease (SD): A 50% decrease in total tumor area cannot be established nor has a 25% increase in the size of one or more measurable lesions been demonstrated.

  3. Relationship Between Response to Everolimus in Combination With Bevacizumab and the Presence of NF1 Mutations or NF1 Inactivation in MPNST Tumor Samples [ Time Frame: greater than or equal to 4 months ]
    To explore the relationship between response to everolimus in combination with bevacizumab and the presence of NF1 mutations or NF1 inactivation in MPNST tumor samples

  4. Vascular Endothelial Growth Factor (VEGF) and Vascular Endothelial Growth Factor Receptor 2 (VEGFR2) Levels at Baseline and Pre-Cycles 3 and 5 [ Time Frame: Baseline, Pre-Cycle 3, Pre-Cycle 5 ]
    To assess changes in Vascular Endothelial Growth Factor (VEGF) and Vascular Endothelial Growth Factor Receptor 2 (VEGFR2) Levels in peripheral blood specimens during treatment.

  5. Utility of 3-D MRI Analysis in Comparison to 1-D and 2-D Measurements to More Sensitively Monitor Response to Everolimus in Combination With Bevacizumab [ Time Frame: greater than or equal to 4 months ]
    To evaluate the utility of 3-D MRI analysis in comparison to 1-D and 2-D measurements to more sensitively monitor response to everolimus in combination with bevacizumab



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
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
  • Eastern Cooperative Oncology Group (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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01661283


Locations
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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, 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
Saint Louis, Missouri, United States, 63130
United States, Ohio
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, United States, 45229-3039
United States, Pennsylvania
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, United States, 19104
Pennsylvania Oncology Hematology Associates
Philadelphia, Pennsylvania, United States, 19106
Sponsors and Collaborators
Sarcoma Alliance for Research through Collaboration
Novartis Pharmaceuticals
Genentech, Inc.
United States Department of Defense
Investigators
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Principal Investigator: Brigitte C. Widemann, MD National Cancer Institute (NCI)
  Study Documents (Full-Text)

Documents provided by Sarcoma Alliance for Research through Collaboration:

Additional Information:
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Responsible Party: Sarcoma Alliance for Research through Collaboration
ClinicalTrials.gov Identifier: NCT01661283     History of Changes
Other Study ID Numbers: SARC016
First Posted: August 9, 2012    Key Record Dates
Results First Posted: March 6, 2019
Last Update Posted: March 6, 2019
Last Verified: February 2019
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:
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Anti-Infective Agents
Sarcoma
Nerve Sheath Neoplasms
Neurofibrosarcoma
Neoplasms
Neoplasms, Connective and Soft Tissue
Neoplasms by Histologic Type
Neoplasms, Nerve Tissue
Peripheral Nervous System Neoplasms
Nervous System Neoplasms
Nervous System Diseases
Peripheral Nervous System Diseases
Neuromuscular Diseases
Fibrosarcoma
Neoplasms, Fibrous Tissue
Neoplasms, Connective Tissue
Neurofibroma
Sirolimus
Bevacizumab
Everolimus
Antineoplastic Agents, Immunological
Antineoplastic Agents
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Physiological Effects of Drugs
Growth Inhibitors
Immunosuppressive Agents
Immunologic Factors
Anti-Bacterial Agents