Neoplasms

All Conditions

Nervous System Diseases

Diseases and Abnormalities at or Before Birth

Skin and Connective Tissue Diseases

Rare Diseases

Sarcoma

Neurofibromatoses

Neurofibromatosis 1

Neurofibroma

Nerve Sheath Neoplasms

Neurofibrosarcoma

Neoplasms, Connective and Soft Tissue

Neoplasms by Histologic Type

Neoplasms, Nerve Tissue

Nervous System Neoplasms

Peripheral Nervous System Neoplasms

Peripheral Nervous System Diseases

Neuromuscular Diseases

Fibrosarcoma

Neoplasms, Fibrous Tissue

Neoplasms, Connective Tissue

Soft Tissue Sarcoma

Neurofibromatosis

Neurofibromatosis Type 1

Malignant Peripheral Nerve Sheath Tumor

Antineoplastic Agents

All Drugs and Chemicals

Anti-Infective Agents

Bevacizumab

Everolimus

Sirolimus

Temsirolimus

MTOR Inhibitors

Antineoplastic Agents, Immunological

Angiogenesis Inhibitors

Growth Inhibitors

Protein Kinase Inhibitors

Enzyme Inhibitors

Immunosuppressive Agents

Immunologic Factors

All patients with MPNST will continue everolimus 10 mg daily and bevacizumab 10 mg/kg dose every 14 days

everolimus

bevacizumab

Brigitte C. Widemann, MD

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

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

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.

To evaluate the spectrum of germline NF1 mutations in individuals with NF1 associated MPNSTs

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.

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

To assess changes in Vascular Endothelial Growth Factor (VEGF) and Vascular Endothelial Growth Factor Receptor 2 (VEGFR2) Levels in peripheral blood specimens during treatment.

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

Novartis Pharmaceuticals

Genentech, Inc.

United States Department of Defense

Sarcoma Alliance for Research through Collaboration

Everolimus (2.5, 5, and 10 mg tablets) was administered at 10 mg per dose once daily at the same time on a continuous dosing schedule.

Bevacizumab (400 mg vials) was administered at 10 mg/kg as intravenous infusion over 30-90 minutes every 2 weeks (days 1 and 15).

One treatment cycle was 28 days.

Treatment

Sporadic

17 patients enrolled with NF1 and 8 patients enrolled with sporadic MPNST.

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

Was the primary tumor resected

Patient had prior chemotherapy

Patient had prior radiation

Eastern Cooperative Oncology Group (ECOG) Performance Status Scale:

Grade 0: Normal activity. Fully active, able to carry on all pre-disease performance without restriction.

Grade 1: Symptoms, but ambulatory. Restricted in physically strenuous activity, but ambulatory and able to carry out work of a light or sedentary nature.

Grade 2: In bed \<50% of the time. Ambulatory and capable of all self-care, but unable to carry out any work activities. Up and about more than 50% of waking hours.

ECOG performance score at baseline

20 subjects had the primary tumor resected out of the 25 total subjects.

Margins of surgical resection

SARC

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

NF1 germline mutations were not analyzed.

Spectrum of Germline NF1 Mutations in Individuals With NF1 Associated MPNSTs

NF1 associated MPNST

Sporadic MPNST

The rows are broken up by patients with NF1 associated MPNST (n=17) and sporadic MPNST (n=8)

Number of Participants With Response Stratified by Individuals With Sporadic or NF1 Associated MPNST

Tumor samples were not analyzed for NF1 mutations.

Relationship Between Response to Everolimus in Combination With Bevacizumab and the Presence of NF1 Mutations or NF1 Inactivation in MPNST Tumor Samples

VEGF- Baseline

VEGF- Pre Cycle 3

VEGF- Pre Cycle 5

VEGFR2- Baseline

VEGFR2 Pre Cycle 3

VEGFR2 Pre Cycle 5

Paired samples for analysis were collected for 14 patients at baseline and time of first restaging and 8 patients at time of second restaging.

Vascular Endothelial Growth Factor (VEGF) and Vascular Endothelial Growth Factor Receptor 2 (VEGFR2) Levels at Baseline and Pre-Cycles 3 and 5

Imaging studies of sufficient quality to analyze tumors were not collected. Therefore, unable to analyze volumes and compare 3-D to 1-D and 2-D measurements.

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

Overall Study

Spots Global Cancer Trial Database for SARC016: Study of Everolimus With Bevacizumab to Treat Refractory Malignant Peripheral Nerve Sheath Tumors

Trial Identification

Conditions

Interventions

Study Description

Keywords

Eligibility

Locations

Contact Details

Useful links and downloads for this trial