Description:
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
Title
- Brief Title: 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
Clinical Trial IDs
- ORG STUDY ID:
SARC016
- NCT ID:
NCT01661283
Conditions
- Malignant Peripheral Nerve Sheath Tumors
- MPNST
- Sarcoma
Interventions
| Drug | Synonyms | Arms |
|---|
| everolimus | Afinitor, everolimus | Arm A |
| bevacizumab | Avastin | Arm A |
Purpose
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
Trial Arms
| Name | Type | Description | Interventions |
|---|
| Arm A | Experimental | All patients with MPNST will continue everolimus 10 mg daily and bevacizumab 10 mg/kg dose every 14 days | |
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
| Maximum Eligible Age: | N/A |
| Minimum Eligible Age: | 18 Years |
| Eligible Gender: | All |
| Healthy Volunteers: | No |
Primary Outcome Measures
| 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 |
| Time Frame: | Assessed at Baseline and prior to Cycle 3, 5, 7, 9, etc., for up to 2 years. 1 cycle =28 days |
| Safety Issue: | |
| Description: | 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
| Measure: | Spectrum of Germline NF1 Mutations in Individuals With NF1 Associated MPNSTs |
| Time Frame: | greater than or equal to 4 months |
| Safety Issue: | |
| Description: | To evaluate the spectrum of germline NF1 mutations in individuals with NF1 associated MPNSTs |
| Measure: | 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 |
| Safety Issue: | |
| Description: | 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. |
| Measure: | 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 |
| Safety Issue: | |
| Description: | 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 |
| Measure: | 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 |
| Safety Issue: | |
| Description: | To assess changes in Vascular Endothelial Growth Factor (VEGF) and Vascular Endothelial Growth Factor Receptor 2 (VEGFR2) Levels in peripheral blood specimens during treatment. |
| 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 |
| Time Frame: | greater than or equal to 4 months |
| Safety Issue: | |
| Description: | 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 |
Details
| Phase: | Phase 2 |
| Primary Purpose: | Interventional |
| Overall Status: | Completed |
| Lead Sponsor: | Sarcoma Alliance for Research through Collaboration |
Trial Keywords
- MPNST
- malignant peripheral nerve sheath tumors
- RAD001
- Everolimus
- Bevacizumab
- Sarcoma
- Avastin
- mTOR inhibitor
Last Updated
March 6, 2019
