Malignant Peripheral Nerve Sheath TumorsPhase 2NCT01661283
SARC016: Study of Everolimus With Bevacizumab to Treat Refractory Malignant Peripheral Nerve Sheath Tumors
A Phase 2 study testing everolimus and bevacizumab in people with Malignant Peripheral Nerve Sheath Tumors and MPNST, run by Sarcoma Alliance for Research through Collaboration at 12 sites in United States.
Trial 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). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Malignant Peripheral Nerve Sheath Tumors, MPNST, Sarcoma
- What is being tested?
- everolimus and bevacizumab
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 25 participants
- Where
- 12 sitesUnited States
- Study dates
- Sep 2012to Dec 2017
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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
Who cannot join
- 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
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- 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
Trial locations and contacts
12 sites in 1 country.
12 sites in 1 country
United States12 sites
University of Michigan
Ann Arbor, Michigan, 48109
Johns Hopkins
Baltimore, Maryland, 21218
National Cancer Institute
Bethesda, Maryland, 20892-1101
University of Alabama at Birmingham
Birmingham, Alabama, 35294-0024
Massachusetts General Hospital
Boston, Massachusetts, 02114
Ann and Robert Lurie Children's Hospital of Chicago
Chicago, Illinois, 60611
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, 45229-3039
University of Iowa
Iowa City, Iowa, 52242
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, 19104
Pennsylvania Oncology Hematology Associates
Philadelphia, Pennsylvania, 19106
Washington University in St. Louis
St Louis, Missouri, 63130
Children's National Medical Center
Washington D.C., District of Columbia, 20010
About this study
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
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
- Being tested
- everolimus, bevacizumab
- Keywords
- MPNST, malignant peripheral nerve sheath tumors, RAD001, Everolimus, Bevacizumab, Sarcoma, Avastin, mTOR inhibitor
- Medical subject headings
- Neurofibrosarcoma, Sarcoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
everolimusDrug
Also called Afinitor, everolimus
10 mg tablet once daily
bevacizumabDrug
Also called Avastin
10 mg/kg dose every 14 days
| Study group | Role | What they receive |
|---|---|---|
| Arm A | Experimental | All patients with MPNST will continue everolimus 10 mg daily and bevacizumab 10 mg/kg dose every 14 days Receives: Drug: everolimus; Drug: bevacizumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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
To evaluate the spectrum of germline NF1 mutations in individuals with NF1 associated MPNSTs
Measured: greater than or equal to 4 months
Number of Participants With Response Stratified by Individuals With Sporadic or NF1 Associated MPNST
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.
Measured: 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
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
Measured: 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
To assess changes in Vascular Endothelial Growth Factor (VEGF) and Vascular Endothelial Growth Factor Receptor 2 (VEGFR2) Levels in peripheral blood specimens during treatment.
Measured: 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
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
Measured: greater than or equal to 4 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Aug 2012 (estimated)
- Study startSep 2012
- Primary completionJun 2017
- Study completionDec 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Malignant Peripheral Nerve Sheath TumorsStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 25 participants (actual)
Sponsor and investigators
- Lead sponsor
- Sarcoma Alliance for Research through Collaboration
- Sponsor type
- University, hospital or other
- Collaborators
- Novartis Pharmaceuticals, Genentech, Inc., United States Department of Defense
- Responsible party
- Sponsor
- Investigators
- Brigitte C. Widemann, MD, Principal investigator, National Cancer Institute (NCI)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01661283
- Sponsor's protocol ID
- SARC016
- Status last verified
- Feb 2019
- First submitted
- 7 Aug 2012
- Last updated
- 6 Mar 2019
- Results posted
- Yes, on ClinicalTrials.gov
Study at a glance
From the registry record, last updated by the sponsor on 6 Mar 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT01661283
- Acronym / sponsor ID
- SARC016
- Conditions
- Malignant Peripheral Nerve Sheath Tumors, MPNST, Sarcoma
- Keywords
- MPNST, malignant peripheral nerve sheath tumors, RAD001, Everolimus, Bevacizumab, Sarcoma, Avastin, mTOR inhibitor
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 25 participants (actual)
- Lead sponsor
- Sarcoma Alliance for Research through CollaborationUniversity, hospital or other
- Collaborators
- Novartis Pharmaceuticals, Genentech, Inc., United States Department of Defense
- Study start
- Sep 2012
- Primary completion
- Jun 2017 (actual)
- Study completion
- Dec 2017 (actual)
- First posted
- 9 Aug 2012 (estimated)
- Results
- Posted 6 Mar 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Arm A | Experimental | Drug: everolimus, Drug: bevacizumabAll patients with MPNST will continue everolimus 10 mg daily and bevacizumab 10 mg/kg dose every 14 days |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- 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
Key exclusion criteria (17 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| everolimusAlso: Afinitor, everolimus10 mg tablet once daily | Drug | Arm A |
| bevacizumabAlso: Avastin10 mg/kg dose every 14 days | Drug | Arm A |
Primary outcome
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.
5 secondary outcomes
Spectrum of Germline NF1 Mutations in Individuals With NF1 Associated MPNSTs
Time frame: greater than or equal to 4 months
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
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
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
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
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Mar 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- SARC WebsiteLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Brigitte C. Widemann, MD principal investigator
National Cancer Institute (NCI)
12 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing everolimus and bevacizumab in people with Malignant Peripheral Nerve Sheath Tumors and MPNST, run by Sarcoma Alliance for Research through Collaboration at 12 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 12 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 6 Mar 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 12 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 6 Mar 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome 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). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Mar 2019.