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Completed

NCT Number: NCT01661283

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

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

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Key information

Conditions

Malignant Peripheral Nerve Sheath Tumors Fibrosarcoma MPNST Neoplasms Neoplasms by Histologic Type Neoplasms, Connective Tissue Neoplasms, Connective and Soft Tissue Neoplasms, Fibrous Tissue Neoplasms, Nerve Tissue Nerve Sheath Neoplasms Nervous System Diseases Nervous System Neoplasms Neurofibroma Neurofibrosarcoma Neuromuscular Diseases Peripheral Nervous System Diseases Peripheral Nervous System Neoplasms Sarcoma

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

University of Alabama at Birmingham, Birmingham, Alabama, United States

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Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

Everolimus

Drug

10 mg tablet once daily

Other names: Afinitor, everolimus

Bevacizumab

Drug

10 mg/kg dose every 14 days

Other names: Avastin

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

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

    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 outcomes

  1. Spectrum of Germline NF1 Mutations in Individuals With NF1 Associated MPNSTs

    Time frame: greater than or equal to 4 months

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

  2. 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

    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.

  3. 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

    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

  4. 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

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

  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

    Time frame: greater than or equal to 4 months

    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

Sponsors and collaborators

Lead sponsor

Sarcoma Alliance for Research through Collaboration

Other

Collaborators

  • Genentech, Inc.
  • Novartis Pharmaceuticals
  • United States Department of Defense

Registry information

Official study 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

Important dates

Study start
2012
Primary completion
2017
Study completion
2017
First posted
Aug 9, 2012
Registry last updated
Mar 6, 2019

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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