Glioblastoma
Conditions
Brief summary
The primary purpose of this study is to test the safety of Pembrolizumab and Temozolomide in treating recurrent glioblastoma and to characterize the effect of this treatment on the participants tumor and immune system..
Detailed description
Participants will undergo screening tests to determine if they are eligible to participate. This will involve a complete history and physical examination, vital signs, blood tests including complete blood count (CBC), and serum chemistry (CMP). Participants will receive one cycle of Temozolomide and Pembrolizumab prior to removing recurrent tumor, followed by three weekly cycles of treatment until progression.
Interventions
DRUGPembrolizumab and Temozolomide
Characterize the safety and immunologic/genomic/metabolomic effects of neoadjuvant Pembrolizumab and Temozolomide in recurrent glioblastoma.
Sponsors
University of Louisville
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
The experience with neoadjuvant immunotherapy has raised the possibility of utilizing surgical resection/immunotherapy as a combination treatment for patients with recurrent glioblastoma. There are several reasons that suggest that surgical resection will likely enhance the activity of immunotherapy in glioblastoma.This includes 1) direct impact on tumor cells; 2) impact on immune cells; and 3) impact on immune infiltration. The combination of the evidence that neoadjuvant Pembrolizumab has a positive effect on GBM survival, the evidence in lung cancer that chemotherapy and checkpoint inhibitor therapies are synergistic and the clinical utility of surgery in patients with recurrent glioblastoma has suggested that the neoadjuvant administration of Pembrolizumab and temozolomide prior to and following maximal surgical resection represents a very attractive experimental combination for the treatment of recurrent glioblastoma.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
-Inclusion Criteria Patients are eligible to be included in the only if they meet all of the following criteria 1. Histopathologically proven diagnosis of glioblastoma prior to registration, by pathology report; 2. The tumor must be confined to the supratentorial compartment 3. The tumor tissue block from the primary diagnosis must be available to be sent for pathology review, after registration. 4. History/physical examination within 7 days prior to registration 5. Karnofsky performance status ≥ 60 within 7 days prior to registration. 6. Adequate Organ Function Laboratory Values * Absolute neutrophil count (ANC) ≥1,500/mcL * Platelets ≥100,000/mcL * Hemoglobin ≥9.0 g/gL or ≥5.6 mmol/L, without recent transfusion * Creatine ≤1.7 x upper limit of normal (ULN) or Measure or Calculated creatinine clearance ≥ 60.0mL/min for subject with creatinine levels \> 1.5 X institutional ULN (GFR can also be used in place of creatinine or CrCl) * Total bilirubin ≤ 1.5 x ULN or Direct bilirubin ≤ ULN for subjects with total bilirubin levels \> 1.5 x ULN * AST (SGOT) and ALT (SGPT) ≤ 2.5 x ULN or ≤ 5 x ULN for subjects with liver metastases 7. The patient must have completed chemoradiation with Radiotherapy and Temozolomide of the primary tumor according to standard of care. 8. Patients must have received no more than 3 prior therapies for Recurrent High Grade Glioma. 9. Subjects must have the ability to understand and willingness to sign a written informed consent document. 10. Female subjects of childbearing potential should have a negative urine or serum pregnancy test within 72 hours prior to receiving the first dose of study medication. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required. 11. Female subjects of childbearing potential should be willing to use 2 methods of birth control or be surgically sterile, or abstain from heterosexual activity for the course of the study through 120 days after the last dose of study medication. 12. Male subjects should agree to use an adequate method of contraception starting with the first dose of study therapy through 120 days after the last dose of study therapy.
Exclusion criteria
-
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Treatment toxicity | Change in frequency of adverse events prior to gross total resection or recurrent glioblastoma | Quantification of the frequency of adverse events in patients treated with neoadjuvant Pembrolizumab and Temozolomide with gross total resection of recurrent glioblastoma. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival | Every 8 weeks for 24 months | Progression and response to treatment will be determined using the Response Assessment in Neuro-Oncology (RANO) criteria. |
| Neurologic function and quality of life | Every 8 weeks for 24 months | Using the Neurologic Assessment in Neuro-oncology (NANO) scale on each visit. In addition, the Eastern Cooperative Oncology Group (ECOG) performance status will be monitored. |
| Treatment Toxicity | Change in frequency of adverse events after gross total resection or recurrent glioblastoma | Quantification of the frequency of adverse events in patients treated with neoadjuvant Pembrolizumab and Temozolomide after gross total resection of recurrent glioblastoma. |
Countries
United States
Contacts
Primary ContactDonald Miller, MD
Outcome results
None listed