Phase 2 N=25 Treatment

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

Malignant Peripheral Nerve Sheath Tumors · MPNST · Sarcoma

Bottom Line

View on ClinicalTrials.gov: NCT01661283 ↗

Enrolled (actual)

Serious AEs

44.0%

Results posted

Mar 2019

Primary outcome: Primary: 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 — 3 Participants

Study Design & Population

Study type: Interventional
Phase: Phase 2
Interventions: everolimus (Drug); bevacizumab (Drug)
Age: Adult, Older Adult · 18+ yrs
Sex: All
Sponsor: Sarcoma Alliance for Research through Collaboration
Primary completion: Jun 2017

Outcome Measures

Outcome	Result	p-value
PRIMARY 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	3	—
SECONDARY Spectrum of Germline NF1 Mutations in Individuals With NF1 Associated MPNSTs	—	—
SECONDARY Number of Participants With Response Stratified by Individuals With Sporadic or NF1 Associated MPNST	2; 1	—
SECONDARY Relationship Between Response to Everolimus in Combination With Bevacizumab and the Presence of NF1 Mutations or NF1 Inactivation in MPNST Tumor Samples	—	—
SECONDARY Vascular Endothelial Growth Factor (VEGF) and Vascular Endothelial Growth Factor Receptor 2 (VEGFR2) Levels at Baseline and Pre-Cycles 3 and 5	103.58; 184.24; 192.49; 1363.76; 911.89; 863.85	—
SECONDARY 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	—	—

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

View full record on ClinicalTrials.gov →

Data sourced from ClinicalTrials.gov (NCT01661283). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.