Avelumab With Hypofractionated Radiation Therapy in Adults With Isocitrate Dehydrogenase (IDH) Mutant Glioblastoma

NCT02968940 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: 16-01179
• Study Type: interventional
• Target: 6
• Locations: 1 country
• Sites: 4

Brief Summary

The purpose of this study is to test how safe and effective treatment with the combination of Avelumab and radiation is for IDH mutant gliomas that have transformed to glioblastoma after chemotherapy.

Conditions

Glioblastoma

Keywords

Programmed cell death protein 1 (PD-1); Programmed death-ligand 1 (PD-L1); Immunotherapy; Hypofractionated Radiotherapy (HFRT); Isocitrate dehydrogenase (IDH); Glioma

Outcome Measures

Primary Outcomes (2)

• Number of Dose Limiting Toxicities

  Subjects are evaluable for DLTs (defined in section 5.2.1.2) if they have received at least one dose of Avelumab, have completed HFRT per protocol and have completed safety assessments over the entire DLT evaluation period (days 1 through 28).

  Day 28

• Median Progression-free Survival (PFS6)

  PFS, defined as the time between treatment initiation and first occurrence of disease progression or death, will be censored at last follow-up if the patient remained alive without disease progression

  Month 6

Secondary Outcomes (2)

• Median Overall Survival (OS)

  Month 12

• Median Progression-free Survival (PFS12)

  Month 12

Study Arms (1)

Avelumab and hypofractionated radiation therapy(HFRT)

EXPERIMENTAL

* Avelumab 10 mg/kg intravenously (IV) every 2 weeks. * Hypofractionated radiation therapy to a total dose of 30 Gy, delivered in 6 Gy per fraction for 5 consecutive daily fractions

Biological: Avelumab; Radiation: Hypofractionated radiation therapy (HFRT)

Interventions

Avelumab BIOLOGICAL

Avelumab 10 mg/kg intravenously (IV) every 2 weeks

Also known as: MSB0010718C

Avelumab and hypofractionated radiation therapy(HFRT)

Hypofractionated radiation therapy (HFRT) RADIATION

Hypofractionated radiation therapy to a total dose of 30 Gy, delivered in 6 Gy per fraction for 5 consecutive daily fractions

Avelumab and hypofractionated radiation therapy(HFRT)

Eligibility Criteria

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

You may qualify if:

• Male or female subjects aged ≥18 years.
• Documentation of IDH1 or IDH2 mutation in any tumor specimen.
• Pathologic evidence (either diagnostic pathology slides or pathology report) of a diagnosis of WHO grade II or III glioma prior to treatment with temozolomide or PCV chemotherapy.
• Histopathological evidence of glioblastoma (WHO grade IV) on a progressive tumor specimen after treatment with temozolomide or PCV chemotherapy. The diagnosis of glioblastoma must be confirmed on central review by a study-designated neuropathologist at NYULMC at screening.
• Exceptions to this eligibility include the following:
• a. Any progressive glioma with IDH1 or IDH2 mutation, regardless of WHO grade, histopathological diagnosis, or prior therapy, will be eligible if the progressive tumor specimen is found to have one of the genetic alterations below:
• ≥20 somatic mutations per Mb by whole-exome sequencing
• High mutation burden or microsatellite instability (MSI) identified by Foundation Medicine panel next-generation sequencing (FoundationOne®, FoundationOne CDx™). Foundation Medicine's threshold for high mutation burden (HMB) in their panel NGS assays is ≥20 somatic mutations per Mb. Foundation Medicine's panel NGS assay has been validated by whole-exome and whole-genome sequencing to correlate tightly with tumor mutation burden (R2 = 0.94).96
• Mutation in a mismatch repair gene or other genes known to be associated with hypermutator phenotypes or microsatellite instability, including but not limited to MSH2, MSH6, MLH1, POLE, PMS2, POLD as determined by validated methods.
• Microsatellite instability as identified by polymerase chain reaction (PCR) or other validated methods.
• b. Progressive oligodendroglioma (with 1p/19q codeletion) that has hallmark histopathological features of glioblastoma (i.e. necrosis, pseudopalisading necrosis, or microvascular proliferation) is eligible as IDH1/2 mutant, 1p/19q codeleted oligodendrogliomas that have progressed after chemotherapy have been shown to develop hypermutation phenotype.
• Criteria 4a. Notes or records from the treating oncologist are required for documentation of treatment history. Prior treatment with at least one of the following chemotherapy schedules is required to be eligible:
• At least one 6 week course of continuous daily temozolomide
• At least six 28-day cycles given in one of the following schedules:
• Daily for 5 days of a 28-day cycle

You may not qualify if:

• Investigational drug use within 28 days of the first dose of Avelumab.
• Planned participation in another study of an investigational agent or investigational device or use of a therapeutic device intended for therapy of glioma.
• Prior therapy with an agent that blocks the PD-1/PD-L1 pathway.
• Primary brainstem or spinal cord tumor.
• Diffuse leptomeningeal disease at recurrence
• Recurrent infratentorial tumor
• Prior re-irradiation or stereotactic radiosurgery for recurrent disease at the same tumor location intended for HFRT in this study.
• Maximal tumor diameter \>4 cm
• Patients with evidence of significant intracranial mass effect that requires \>4 mg of dexamethasone or bioequivalent per day for 5 consecutive days for management of symptoms at any time within 14 days of registration.
• Subjects on a standard high-dose steroid taper after craniotomy may receive a higher dose of corticosteroids within 14 days of registration, however must be at a dose ≤4 mg of dexamethasone or bioequivalent per day within 5 days prior to registration.
• Administration of steroids through a route known to result in a minimal systemic exposure \[i.e., intranasal, intraocular, inhaled, topical, or local injection (e.g., intra-articular injection) corticosteroids (\<5% of body surface area)\] are permitted.
• Subjects requiring hormone replacement with corticosteroids are eligible if the steroids are at doses ≤ 10 mg prednisone or bioequivalent per day.
• Steroids as premedication for hypersensitivity reactions (e.g., CT scan premedication) are allowed.
• a. Patients with diabetes type I, vitiligo, hypo- or hyperthyroid diseases, or psoriasis not requiring systemic immunosuppressive treatment are eligible.
• Prior organ transplantation, including allogeneic stem cell transplantation.

Sponsors & Collaborators

• NYU Langone Health: lead
• EMD Serono: collaborator

Study Sites (4)

University of California, Los Angeles (UCLA)

Los Angeles, California, 90095, United States

Location

UCSF Medical Center

San Francisco, California, 94143, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Laura & Isaac Perlmutter Cancer Center & NYU Langone Medical Center

New York, New York, 10016, United States

Location

MeSH Terms

Conditions

Glioblastoma; Parkinson Disease 4, Autosomal Dominant Lewy Body; Glioma

Interventions

avelumab

Condition Hierarchy (Ancestors)

Astrocytoma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Results Point of Contact

• Title: Sylvia Kurz, MD, PhD
• Organization: NYU Langone Health - Perlmutter Cancer Center

Sylvia.Kurz@nyulangone.org

212-731-6267

Study Officials

• Sylvia Kurz, MD

  NYU Perlmutter Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

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: November 17, 2016
• First Posted: November 21, 2016
• Study Start: March 17, 2017
• Primary Completion: August 29, 2019
• Study Completion: August 29, 2019
• Last Updated: June 29, 2022
• Results First Posted: June 29, 2022

Record last verified: 2022-06

Locations

US (4)