Phase 2
Completed N=25
SARC016: Study of Everolimus With Bevacizumab to Treat Refractory Malignant Peripheral Nerve Sheath Tumors
Malignant Peripheral Nerve Sheath Tumors · MPNST · sarcoma
Source: ClinicalTrials.gov NCT01661283 ↗
Enrolled (actual)
25
Serious AEs
44.0%
Results posted
Mar 2019
Primary outcomePrimary: 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
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
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 |
— | — |
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
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. Informational only — not medical advice.