Phase I Study of PD-L1 Inhibition With Avelumab and Laser Interstitial Thermal Therapy in Patients With Recurrent Glioblastoma
Trial Snapshot
- Phase
- Phase 1
- Status
- Completed
- Enrollment
- 13
- Locations
- 1
- Primary Endpoint
- Dose Limiting Toxicity level
Study Overview
Brief Summary
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.
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 Design
- Study Type
- Interventional
- Allocation
- Na
- Intervention Model
- Single Group
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
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
- •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.
Arms & Interventions
Patients with Recurrent Glioblastoma
Part A - Avelumab Part B - Avelumab + MRI-guided LITT therapy
Intervention: Avelumab (Drug)
Patients with Recurrent Glioblastoma
Part A - Avelumab Part B - Avelumab + MRI-guided LITT therapy
Intervention: MRI-guided LITT therapy (Combination Product)
Outcomes
Primary Outcomes
Dose Limiting Toxicity level
Time Frame: 4 weeks
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.
Objective response rate (ORR)
Time Frame: 6 months
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)
Secondary Outcomes
- Progression-free survival(6 months)
- Overall response rate(6 months)
Investigators
Adilia Hormigo
Associate Professor
Icahn School of Medicine at Mount Sinai