GBM, Glioblastoma
Conditions
Keywords
GBM, LITT, Laser Interstitial Thermal Therapy, Bavencio, immunotherapy
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.
Interventions
DRUGAvelumab
Avelumab will be administered intravenously every 2 weeks at a dose of 10 mg/kg for 2 cycles
COMBINATION_PRODUCTMRI-guided LITT therapy
(Part B) prior to receiving Avelumab 10 mg/kg every 2 weeks + LITT
Sponsors
Icahn School of Medicine at Mount Sinai
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
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 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Dose Limiting Toxicity level | 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) | 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
| Measure | Time frame | Description |
|---|---|---|
| Progression-free survival | 6 months | The % of progression free survival at 6 months |
| Overall response rate | 6 months | Overall response rate (proportion of partial and complete responses) will be evaluated according to Rano criteria. |
Countries
United States
Outcome results
None listed