Neoadjuvant Avelumab and Hypofractionated Proton Radiation Therapy Followed by Surgery for Recurrent Radiation-refractory Meningioma

NCT03267836

Last updated date
Study Location
Washington University School of Medicine
Saint Louis, Missouri, 63110, United States
Contact
314-362-8567

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Eligibility Criteria
condition
The disease, disorder, syndrome, illness, or injury that is being studied.
Meningioma, Adult Meningioma
Sex
Females and Males
Age
Pediatric Trials: 0-17 Years
Adult Trials: 18+ Years
18 + years
Inclusion Criteria
The factors, or reasons, that allow a person to participate in a clinical study.
Show details

- 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)

Exclusion Criteria
The factors, or reasons, that prevent a person from participating in a clinical study.
Show details


- 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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Meningioma, Adult MeningiomaNeoadjuvant Avelumab and Hypofractionated Proton Radiation Therapy Followed by Surgery for Recurrent Radiation-refractory Meningioma
NCT03267836
  1. Saint Louis, Missouri
ALL GENDERS
18 Years+
years
MULTIPLE SITES
Advanced Information
Descriptive Information
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
  • Meningioma
  • Meningioma, Adult
Intervention  ICMJE
  • Drug: Avelumab
    -10mg/kg IV
    Other Name: Bavencio
  • Radiation: Proton Therapy
    -Proton therapy will start concurrently with the first dose of avelumab (up to 3 days before or after is permissible) and will be administered once daily during weekdays (Monday through Friday).
  • Procedure: Surgery
    -Standard of care
Study Arms  ICMJE Experimental: Avelumab + Proton Therapy
  • Avelumab will be started concurrently with proton therapy (up to 3 days before or after is permissible) and administered every 2 weeks for 3 months
  • Proton therapy 20 CGE (cobalt gray equivalent) will be given over 5 daily fractions of 4 CGE per day during weekdays
  • After 3 months of avelumab, patient will have a brain MRI evaluation, and radiological response will be assigned based on the iRANO criteria. Surgery will be performed as per routine clinical care
  • If the brain MRI after 3 months of avelumab shows complete response with no signs of residual tumor, no surgery will be indicated, and the patient may continue to take adjuvant avelumab for an additional 3 months.
  • After the patient has recovered from the surgery and if deemed medically eligible by the treating physician to receive additional immunotherapy, avelumab will be restarted and administered every 2 weeks for an additional 3 months
Interventions:
  • Drug: Avelumab
  • Radiation: Proton Therapy
  • Procedure: Surgery
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
 (submitted: August 29, 2017)
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:

  • 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 × 10? cells per L
    • Platelet count ? 100 × 10? 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)

Exclusion Criteria:

  • 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.
Sex/Gender  ICMJE
Sexes Eligible for Study:All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Jiayi Huang, M.D.314-362-8567[email protected]
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
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: Yes
Product Manufactured in and Exported from the U.S.: Yes
IPD Sharing Statement  ICMJE
Plan to Share IPD:No
Responsible Party Washington University School of Medicine
Study Sponsor  ICMJE Washington University School of Medicine
Collaborators  ICMJE Pfizer
Investigators  ICMJE
Principal Investigator:Jiayi Huang, M.D.Washington University School of Medicine
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