Clinical trial NCT01661283: SARC016: Study of Everolimus With Bevacizumab to Treat Refractory Malignant Peripheral Nerve Sheath Tumors
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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Malignant Peripheral Nerve Sheath Tumors
MPNST
Sarcoma
Keywords: MPNST
malignant peripheral nerve sheath tumors
RAD001
Everolimus
Bevacizumab
Sarcoma
Avastin
mTOR inhibitor
Lead sponsor: Sarcoma Alliance for Research through Collaboration
Sponsor class: OTHER
Collaborators: name: Novartis Pharmaceuticals
name: Genentech, Inc.
name: United States Department of Defense
First posted: 2012-08-09
Enrollment: 25
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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


Eligibility 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

Primary outcomes:
measure: 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
timeFrame: Assessed at Baseline and prior to Cycle 3, 5, 7, 9, etc., for up to 2 years. 1 cycle =28 days
Secondary outcomes:
measure: Spectrum of Germline NF1 Mutations in Individuals With NF1 Associated MPNSTs
timeFrame: greater than or equal to 4 months
measure: Number of Participants With Response Stratified by Individuals With Sporadic or NF1 Associated MPNST
timeFrame: Assessed at Baseline and prior to Cycle 3, 5, 7, 9, etc., for up to 2 years. 1 cycle =28 days
measure: Relationship Between Response to Everolimus in Combination With Bevacizumab and the Presence of NF1 Mutations or NF1 Inactivation in MPNST Tumor Samples
timeFrame: greater than or equal to 4 months
measure: Vascular Endothelial Growth Factor (VEGF) and Vascular Endothelial Growth Factor Receptor 2 (VEGFR2) Levels at Baseline and Pre-Cycles 3 and 5
timeFrame: Baseline, Pre-Cycle 3, Pre-Cycle 5
measure: 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
timeFrame: greater than or equal to 4 months
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham
state: Alabama
city: Washington
country: United States
facility: Children's National Medical Center
state: District of Columbia
city: Chicago
country: United States
facility: Ann and Robert Lurie Children's Hospital of Chicago
state: Illinois
city: Iowa City
country: United States
facility: University of Iowa
state: Iowa
city: Baltimore
country: United States
facility: Johns Hopkins
state: Maryland
city: Bethesda
country: United States
facility: National Cancer Institute
state: Maryland
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Ann Arbor
country: United States
facility: University of Michigan
state: Michigan
city: Saint Louis
country: United States
facility: Washington University in St. Louis
state: Missouri
city: Cincinnati
country: United States
facility: Cincinnati Children's Hospital Medical Center
state: Ohio
city: Philadelphia
country: United States
facility: Children's Hospital of Philadelphia
state: Pennsylvania
city: Philadelphia
country: United States
facility: Pennsylvania Oncology Hematology Associates
state: Pennsylvania
Study officials:
affiliation: National Cancer Institute (NCI)
name: Brigitte C. Widemann, MD
role: PRINCIPAL_INVESTIGATOR
References: