Neoadjuvant Avelumab and Hypofractionated Proton Radiation Therapy Followed by Surgery for Recurrent Radiation-refractory Meningioma
NCT03267836
ABOUT THIS STUDY
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- Diagnosis of recurrent or progressive histologically confirmed WHO grade I-III meningioma which has failed maximal safe resection and radiation therapy.
- At least one prior surgery with available archival formalin-fixed paraffin-embedded (FFPE) tumor blocks. In the case that tumor block is unavailable, unstained tissue sections may be used in its place.
- Prior treatment must include external beam radiation, radiosurgery, or combination of both.
- Deemed eligible for additional partial resection by treating physician and determined to be safe to receive 3 months of neoadjuvant therapy before planned surgery.
- Age ≥ 18 years old. 6. Karnofsky performance status (KPS) ≥ 60.
- Adequate organ and bone marrow function (as defined by the following laboratory values):
- Absolute neutrophil count ≥ 1.5 × 10⁹ cells per L
- Platelet count ≥ 100 × 10⁹ platelets per L
- Hemoglobin ≥ 9 g/dL but transfusion allowed
- Total bilirubin concentration of ≤ 1.5 × the upper limit of normal [ULN] range
- Aspartate aminotransferase and alanine aminotransferase concentrations of ≤ 2.5 × ULN)
- Estimated creatinine clearance ≥ 30 mL/min according to the Cockcroft-Gault formula.
- Dexamethasone dose ≤ 4mg daily.
- Women of childbearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control, abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while participating in the study, she must inform her treating physician immediately.
- Able to understand and willing to sign an IRB approved written informed consent document (or legally authorized representative, if applicable)
- Previous treatment with PD-1 or PD-L1 directed therapy.
- Active infection requiring systemic therapy.
- Uncontrolled intercurrent illness including, but not limited to, clinically
significant (i.e. active) cardiovascular disease: cerebral vascular accident/stroke (<
6 months prior to enrollment), myocardial infarction (< 6 months prior to enrollment),
congestive heart failure (≥ NYHA class II), unstable angina pectoris, or serious
cardiac arrhythmia requiring medication.
- Known history of testing positive for human immunodeficiency virus (HIV) or known
acquired immunodeficiency syndrome (AIDS).
- Hepatitis B virus (HBV) or hepatitis C virus (HCV) infection at screening (positive
HBV surface antigen or HCV RNA if anti-HCV antibody screening test positive).
- Currently receiving any other investigational agents.
- Current use of immunosuppressive medication, EXCEPT for the following:
- Intranasal, inhaled, topical steroids, or local steroid injection (e.g.
intra-articular injection)
- Systemic corticosteroids at physiologic doses ≤ 10 mg/day of prednisone or
equivalent
- Steroids as premedication for hypersensitivity reactions (e.g. CT scan
premedication)
- Active autoimmune disease that might deteriorate when receiving an immuno-stimulatory
agent. Patients with diabetes type I, vitiligo, psoriasis, or hypo- or hyperthyroid
disease not requiring immunosuppressive treatment are eligible.
- Prior organ transplantation including allogeneic stem cell transplantation.
- Other severe acute or chronic medical conditions including immune colitis,
inflammatory bowel disease, immune pneumonitis, pulmonary fibrosis, or psychiatric
conditions including recent (within the past year) or active suicidal ideation or
behavior, or laboratory abnormalities that may increase the risk associated with study
participation or study treatment administration or may interfere with the
interpretation of study results and, in the judgment of the investigator, would make
the patient inappropriate for entry into this study.
- Vaccination within 4 weeks of the first dose of avelumab and while on trial is
prohibited except for administration of inactivated vaccines.
- History of allergic reactions or hypersensitivity attributed to compounds of similar
chemical or biologic composition to avelumab or other agents used in the study (or
monoclonal antibodies).
- Persisting toxicity related to prior therapy (CTCAE > grade 1); however, alopecia,
sensory neuropathy ≤ grade 2, or other ≤ grade 2 not constituting a safety risk based
on the investigator's judgment are acceptable.
- Pregnant and/or breastfeeding. Women of childbearing potential must have a negative
pregnancy test within 14 days of study entry.
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Descriptive Information | |||||||
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Brief Title ICMJE | Neoadjuvant Avelumab and Hypofractionated Proton Radiation Therapy Followed by Surgery for Recurrent Radiation-refractory Meningioma | ||||||
Official Title ICMJE | A Phase Ib Study of Neoadjuvant Avelumab and Hypofractionated Proton Radiation Therapy Followed by Surgery for Recurrent Radiation-refractory Meningioma | ||||||
Brief Summary | Meningioma is the most common central nervous system (CNS) tumor and accounts for approximately 30% of all CNS tumors. For meningioma recurring after surgery and radiation therapy, there is no effective medical therapy. Repeat surgery or radiation therapy may be possible, but they are temporizing measures with limited durable relief. PD-L1 expression in meningioma is increased for recurrent tumors or prior radiation therapy, and a recent case study reported significant reduction of an intracranial meningioma after 6 months of PD-L1 blockade. Radiation has been shown to augment immune response when combined with PD-L1 blockade. Proton radiation therapy has higher relative biological effectiveness (RBE) and may further amplify the above immunological signals. Combination of proton radiation therapy administered concurrently with PD-L1 inhibitor may maximize immune response for recurrent meningioma. However, confirmation of the increased immunogenicity or increased tumor infiltrating lymphocytes using the combination of radiation therapy and PD-L1 blockade have not been confirmed in patients. The proposed study will be a single institution, single-arm, open-label, phase Ib study to combine neoadjuvant avelumab (a PD-L1 inhibitor) with hypofractionated proton therapy of 20 CGE (cobalt gray equivalent) over 5 fractions followed by planned surgery for recurrent radiation-refractory meningioma. This study is designed to provide proof of concept to demonstrate on-target effect of the combination to increase immunogenicity by directly examining the resected tumor for immune response and to evaluate preliminary clinical efficacy | ||||||
Detailed Description | Not Provided | ||||||
Study Type ICMJE | Interventional | ||||||
Study Phase ICMJE | Phase 1 | ||||||
Study Design ICMJE | Allocation: N/A Intervention Model: Single Group Assignment Masking: None (Open Label) Primary Purpose: Treatment | ||||||
Condition ICMJE |
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Intervention ICMJE |
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Study Arms ICMJE | Experimental: Avelumab + Proton Therapy
Interventions:
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Publications * | Not Provided | ||||||
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline. | |||||||
Recruitment Information | |||||||
Recruitment Status ICMJE | Recruiting | ||||||
Estimated Enrollment ICMJE | 12 | ||||||
Original Estimated Enrollment ICMJE | Same as current | ||||||
Estimated Study Completion Date ICMJE | July 31, 2022 | ||||||
Estimated Primary Completion Date | July 31, 2022 (Final data collection date for primary outcome measure) | ||||||
Eligibility Criteria ICMJE | Inclusion Criteria:
Exclusion Criteria:
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Sex/Gender ICMJE |
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Ages ICMJE | 18 Years and older (Adult, Older Adult) | ||||||
Accepts Healthy Volunteers ICMJE | No | ||||||
Contacts ICMJE |
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Listed Location Countries ICMJE | United States | ||||||
Removed Location Countries | |||||||
Administrative Information | |||||||
NCT Number ICMJE | NCT03267836 | ||||||
Other Study ID Numbers ICMJE | 201711195 | ||||||
Has Data Monitoring Committee | Yes | ||||||
U.S. FDA-regulated Product |
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IPD Sharing Statement ICMJE |
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Responsible Party | Washington University School of Medicine | ||||||
Study Sponsor ICMJE | Washington University School of Medicine | ||||||
Collaborators ICMJE | Pfizer | ||||||
Investigators ICMJE |
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PRS Account | Washington University School of Medicine | ||||||
Verification Date | September 2020 | ||||||
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP |