- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01661283
SARC016: Study of Everolimus With Bevacizumab to Treat Refractory Malignant Peripheral Nerve Sheath Tumors
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 Overview
Status
Conditions
Intervention / Treatment
Study Type
Enrollment (Actual)
Phase
- Phase 2
Contacts and Locations
Study Locations
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Alabama
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Birmingham, Alabama, United States, 35294-0024
- University of Alabama at Birmingham
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District of Columbia
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Washington, District of Columbia, United States, 20010
- Children's National Medical Center
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Illinois
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Chicago, Illinois, United States, 60611
- Ann and Robert Lurie Children's Hospital of Chicago
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Iowa
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Iowa City, Iowa, United States, 52242
- University of Iowa
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Maryland
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Baltimore, Maryland, United States, 21218
- Johns Hopkins
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Bethesda, Maryland, United States, 20892-1101
- National cancer institute
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Massachusetts
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Boston, Massachusetts, United States, 02114
- Massachusetts General Hospital
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Michigan
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Ann Arbor, Michigan, United States, 48109
- University of Michigan
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Missouri
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Saint Louis, Missouri, United States, 63130
- Washington University in St. Louis
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Ohio
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Cincinnati, Ohio, United States, 45229-3039
- Cincinnati Children's Hospital Medical Center
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Pennsylvania
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Philadelphia, Pennsylvania, United States, 19104
- Children's Hospital of Philadelphia
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Philadelphia, Pennsylvania, United States, 19106
- Pennsylvania Oncology Hematology Associates
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
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
Study Plan
How is the study designed?
Design Details
- Primary Purpose: TREATMENT
- Allocation: NA
- Interventional Model: SINGLE_GROUP
- Masking: NONE
Arms and Interventions
Participant Group / 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
|
10 mg tablet once daily
Other Names:
10 mg/kg dose every 14 days
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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. |
Assessed at Baseline and prior to Cycle 3, 5, 7, 9, etc., for up to 2 years. 1 cycle =28 days
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Spectrum of Germline NF1 Mutations in Individuals With NF1 Associated MPNSTs
Time Frame: greater than or equal to 4 months
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To evaluate the spectrum of germline NF1 mutations in individuals with NF1 associated MPNSTs
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greater than or equal to 4 months
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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.
|
Assessed at Baseline and prior to Cycle 3, 5, 7, 9, etc., for up to 2 years. 1 cycle =28 days
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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
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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
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greater than or equal to 4 months
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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
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To assess changes in Vascular Endothelial Growth Factor (VEGF) and Vascular Endothelial Growth Factor Receptor 2 (VEGFR2) Levels in peripheral blood specimens during treatment.
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Baseline, Pre-Cycle 3, Pre-Cycle 5
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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
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greater than or equal to 4 months
|
Collaborators and Investigators
Publications and helpful links
Helpful Links
Study record dates
Study Major Dates
Study Start
Primary Completion (ACTUAL)
Study Completion (ACTUAL)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (ESTIMATE)
Study Record Updates
Last Update Posted (ACTUAL)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Nervous System Diseases
- Neoplasms, Connective and Soft Tissue
- Neoplasms by Histologic Type
- Neoplasms
- Neuromuscular Diseases
- Neoplasms, Nerve Tissue
- Peripheral Nervous System Diseases
- Nervous System Neoplasms
- Neoplasms, Connective Tissue
- Peripheral Nervous System Neoplasms
- Neoplasms, Fibrous Tissue
- Fibrosarcoma
- Neurofibroma
- Sarcoma
- Nerve Sheath Neoplasms
- Neurofibrosarcoma
- Physiological Effects of Drugs
- Antineoplastic Agents
- Immunosuppressive Agents
- Immunologic Factors
- Antineoplastic Agents, Immunological
- Angiogenesis Inhibitors
- Angiogenesis Modulating Agents
- Growth Substances
- Growth Inhibitors
- Bevacizumab
- Everolimus
Other Study ID Numbers
- SARC016
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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