Avelumab With Laser Interstitial Therapy for Recurrent Glioblastoma

Phase I Study of PD-L1 Inhibition With Avelumab and Laser Interstitial Thermal Therapy in Patients With Recurrent Glioblastoma

The purpose of the study is to characterize the safety and tolerability of avelumab in combination with Laser Interstitial Thermal Therapy (LITT) for blood barrier disruption in patients with recurrent glioblastoma.

Study Overview

• Status: Completed
• Conditions: Glioblastoma; GBM
• Intervention / Treatment: Drug: Avelumab; Combination product: MRI-guided LITT therapy

Detailed Description

This is an open label, non-randomized Phase I study of intravenous avelumab every 2 weeks to be administered after real-time MRI-guided LITT therapy for patients with a first recurrence of a glioblastoma.

The primary objective of the study is to characterize the tolerability and safety profile of avelumab in combination with MRI guided LITT administered to patients diagnosed with recurrent GBM.

Part A, the initial cohort of patients will be treated with intravenous avelumab alone. Part B, patients will receive avelumab in combination with MRI-guided LITT to characterize the tolerability and safety of the combined treatment.

• Study Type: Interventional
• Enrollment (Actual): 13
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • New York
    • New York, New York, United States, 10029
      • Icahn School of Medicine at Mount Sinai

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patients must have histologically proven GBM from the initial resection.
• Patients must have a life expectancy > 16 weeks. Patients must have a Karnofsky performance status of ≥ 60 or ECOG 0 - 2
• Patient's requirement for dexamethasone should be ≤ 4mg daily or a stable dose at enrollment.
• Patients must have adequate bone marrow, hepatic and renal function and hemoglobin and the test musts be performed within 14 days prior to study Day 1.
• Highly effective contraception for both male and female subjects if the risk of conception exists.

Exclusion Criteria:

• Known history of autoimmune disorder except diabetes mellitus type 1, vitiligo or hypothyroidism only requiring hormone replacement
• Patients who have received any other therapeutic investigational agent within 30 days of enrollment with the exception of the personalized MTA vaccine (NCT03223103) that can be continued throughout the study.
• Patients who have received any other therapeutic investigational agent within 30 days of enrollment or prior
• Prior placement of intracavitary BCNU-impregnated wafers (Gliadel).
• Prior treatment with checkpoint inhibitors, CTL-4 antibody or other immunotherapy agents
• Presence of any other active malignancy or prior history of malignancy, except for: basal cell carcinoma of the skin, cervical carcinoma in situ, early stage prostate carcinoma not requiring active treatment.
• Prior organ transplantation, including allogeneic stem cell transplantation
• Significant acute or chronic infections including, among others: HIV, AIDS, HBV
• Pregnancy or lactation

Contact site for full inclusion/exclusion list.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Patients with Recurrent Glioblastoma; Part A - Avelumab Part B - Avelumab + MRI-guided LITT therapy	Drug: Avelumab; Avelumab will be administered intravenously every 2 weeks at a dose of 10 mg/kg for 2 cycles; Combination product: MRI-guided LITT therapy; (Part B) prior to receiving Avelumab 10 mg/kg every 2 weeks + LITT

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Dose Limiting Toxicity level	Toxicity will be measured by severity of Adverse events with toxicity grading defined by Cancer Therapy Evaluation Program's (CTEP) v4.0 of National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) scale.	4 weeks
Objective response rate (ORR)	Tumor response to treatment with avelumab in combination with MRI-guided LITT administered to patients with recurrent GBM by estimation of the objective response rate (ORR) -classified according to the RANO Response Criteria (Proportion of Complete Response, Partial Response, Stable Disease and Progressive Disease)	6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-free survival	The % of progression free survival at 6 months	6 months
Overall response rate	Overall response rate (proportion of partial and complete responses) will be evaluated according to Rano criteria.	6 months

Collaborators and Investigators

• Sponsor: Icahn School of Medicine at Mount Sinai
• Investigators: Principal Investigator: Adilia Hormigo, MD, PhD, Icahn School of Medicine at Mount Sinai

Study record dates

Study Major Dates

• Study Start (Actual): June 13, 2018
• Primary Completion (Actual): October 13, 2021
• Study Completion (Actual): October 13, 2021

Study Registration Dates

• First Submitted: November 9, 2017
• First Submitted That Met QC Criteria: November 9, 2017
• First Posted (Actual): November 14, 2017

Study Record Updates

• Last Update Posted (Actual): January 4, 2022
• Last Update Submitted That Met QC Criteria: December 31, 2021
• Last Verified: December 1, 2021

More Information

Terms related to this study

• Keywords: immunotherapy; GBM; LITT; Laser Interstitial Thermal Therapy; Bavencio
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Glioblastoma; Antineoplastic Agents; Antineoplastic Agents, Immunological; Avelumab
• Other Study ID Numbers: GCO 17-1866

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No