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

NCT01661283 | Completed Phase 2 Results

• 1 other identifier: SARC016
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 12

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

Conditions

Malignant Peripheral Nerve Sheath Tumors; MPNST; Sarcoma

Keywords

MPNST; malignant peripheral nerve sheath tumors; RAD001; Everolimus; Bevacizumab; Sarcoma; Avastin; mTOR inhibitor

Outcome Measures

Primary Outcomes (1)

• 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

  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.

  Assessed at Baseline and prior to Cycle 3, 5, 7, 9, etc., for up to 2 years. 1 cycle =28 days

Secondary Outcomes (5)

• Spectrum of Germline NF1 Mutations in Individuals With NF1 Associated MPNSTs

  greater than or equal to 4 months

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

  Assessed at Baseline and prior to Cycle 3, 5, 7, 9, etc., for up to 2 years. 1 cycle =28 days

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

  greater than or equal to 4 months

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

  Baseline, Pre-Cycle 3, Pre-Cycle 5

• 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

  greater than or equal to 4 months

Study Arms (1)

Arm A

EXPERIMENTAL

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

Drug: everolimus; Drug: bevacizumab

Interventions

everolimus DRUG

10 mg tablet once daily

Also known as: Afinitor, everolimus

Arm A

bevacizumab DRUG

10 mg/kg dose every 14 days

Also known as: Avastin

Arm A

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Sarcoma Alliance for Research through Collaboration: lead
• Novartis Pharmaceuticals: collaborator
• Genentech, Inc.: collaborator
• United States Department of Defense: collaborator

Study Sites (12)

University of Alabama at Birmingham

Birmingham, Alabama, 35294-0024, United States

Location

Children's National Medical Center

Washington D.C., District of Columbia, 20010, United States

Location

Ann and Robert Lurie Children's Hospital of Chicago

Chicago, Illinois, 60611, United States

Location

University of Iowa

Iowa City, Iowa, 52242, United States

Location

Johns Hopkins

Baltimore, Maryland, 21218, United States

Location

National Cancer Institute

Bethesda, Maryland, 20892-1101, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

University of Michigan

Ann Arbor, Michigan, 48109, United States

Location

Washington University in St. Louis

St Louis, Missouri, 63130, United States

Location

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, 45229-3039, United States

Location

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, 19104, United States

Location

Pennsylvania Oncology Hematology Associates

Philadelphia, Pennsylvania, 19106, United States

Location

Related Links

• SARC Website

MeSH Terms

Conditions

Neurofibrosarcoma; Sarcoma

Interventions

Everolimus; Bevacizumab

Condition Hierarchy (Ancestors)

Fibrosarcoma; Neoplasms, Fibrous Tissue; Neoplasms, Connective Tissue; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Neurofibroma; Nerve Sheath Neoplasms; Neoplasms, Nerve Tissue; Peripheral Nervous System Neoplasms; Nervous System Neoplasms; Nervous System Diseases; Peripheral Nervous System Diseases; Neuromuscular Diseases

Intervention Hierarchy (Ancestors)

Sirolimus; Macrolides; Lactones; Organic Chemicals; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: SARC
• Organization: SARC

sarc@sarctrials.org

(734) 930-7600

Study Officials

• Brigitte C. Widemann, MD

  National Cancer Institute (NCI)

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 7, 2012
• First Posted: August 9, 2012
• Study Start: September 1, 2012
• Primary Completion: June 1, 2017
• Study Completion: December 1, 2017
• Last Updated: March 6, 2019
• Results First Posted: March 6, 2019

Record last verified: 2019-02

Locations

US (12)