GlioblastomaPhase 1NCT05700955
Neoadjuvant Chemoimmunotherapy in Recurrent Glioblastoma
A Phase 1 study testing Pembrolizumab and Temozolomide in people with Glioblastoma, run by University of Louisville at 1 site in United States.
Trial 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.. Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- Glioblastoma
- What is being tested?
- Pembrolizumab and Temozolomide
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 30 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Nov 2022to Jan 2025
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- -Inclusion Criteria Patients are eligible to be included in the only if they meet all of the following criteria
- Histopathologically proven diagnosis of glioblastoma prior to registration, by pathology report;
- The tumor must be confined to the supratentorial compartment
- The tumor tissue block from the primary diagnosis must be available to be sent for pathology review, after registration.
- History/physical examination within 7 days prior to registration
- Karnofsky performance status ≥ 60 within 7 days prior to registration.
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- 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
- The patient must have completed chemoradiation with Radiotherapy and Temozolomide of the primary tumor according to standard of care.
- Patients must have received no more than 3 prior therapies for Recurrent High Grade Glioma.
- Subjects must have the ability to understand and willingness to sign a written informed consent document.
- 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.
- 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.
- 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.
Who cannot join
- -Exclusion Criteria Patients will be excluded from the study if they meet any of the following criteria
- Previous use of an immunotherapy such as a vaccine therapy, dendritic cell vaccine or intracavitary or convectional enhanced delivery of therapy.
- Prior invasive malignancy (except non-melanomatous skin cancer) within the previous three years
- Severe, active co-morbidity defined as follows:
- Transmural myocardial infarction or unstable angina within the last 6 months prior to registration
- History of stroke, cerebral vascular accident (CVA) or transient ischemic attack within 6 months prior to registration
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- Significant vascular disease (e.g., aortic aneurysm, history of aortic dissection) or clinically significant peripheral vascular disease
- Known history of Tuberculosis or acute bacterial or fungal infection requiring intravenous antibiotics at the time of registration
- Chronic obstructive pulmonary disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy at the time of registration
- Patients with active autoimmune disease or history of autoimmune disease that might recur, will be considered on an individual basis
- Any other major medical illnesses or psychiatric impairments that in the investigator's opinion will prevent administration or completion of protocol therapy.
- Is pregnant or breastfeeding
- Has received prior therapy with an anti-Programmed Death 1 (PD-1), anti- Programmed Death-ligand 1 (PD-L1), or anti- Programmed Death-ligand 1 (PD-L2) agent.
- Patient must have < 1.5 cm midline shift pre-operative
- History of severe hypersensitivity reaction to any monoclonal antibody including pembrolizumab.
- Patients who cannot safely undergo MRI due to non-MRI compatible pacemaker, or other reason.
Trial locations and contacts
1 site in 1 country.
United States1 site, 1 recruiting
- Recruiting
James Graham Brown Cancer Ctr.
Louisville, Kentucky, 40202
Donald Miller, MD, 502-562-4370, Donald.miller@louisville.edu
Donald Miller, MD
About this study
Official title: A Phase I Trial of Neoadjuvant Chemoimmunotherapy in Recurrent Glioblastoma
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..
Read the 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.
- Conditions
- Glioblastoma
- Being tested
- Pembrolizumab and Temozolomide
- Medical subject headings
- Glioblastoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Pembrolizumab and TemozolomideDrug
Also called Pembro and Temodar
Characterize the safety and immunologic/genomic/metabolomic effects of neoadjuvant Pembrolizumab and Temozolomide in recurrent glioblastoma.
| Study group | Role | What they receive |
|---|---|---|
| temozolomide | Experimental | Participants will take Temozolomide pills at home at a dose determined by body weight. They will take the pills for five days every 3 weeks. It will be dispensed by the pharmacy and must be stored in a closed container at room temperature, away from heat, moisture, and direct light and kept from freezing. It will be kept out of the reach of children. Outdated medicine or medicine no longer needed will be returned to the Brown Cancer Center pharmacy for disposal. Receives: Drug: Pembrolizumab and Temozolomide |
| Pembrolizumab | Experimental | Pembrolizumab will be administered at a dose of 200 mg as an IV infusion through a freely flowing IV. The diluted solution will be administered intravenously over 30 minutes through an intravenous line containing a sterile, non-pyrogenic, low-protein binding 0.2 micron to 5 micron in-line or add-on filter. Other drugs will not be co-administered through the same infusion line. Pembrolizumab doses will be repeated every three weeks. Receives: Drug: Pembrolizumab and Temozolomide |
What is being measured
The primary outcome is the main question the study is designed to answer.
Treatment toxicity
Quantification of the frequency of adverse events in patients treated with neoadjuvant Pembrolizumab and Temozolomide with gross total resection of recurrent glioblastoma.
Measured: Change in frequency of adverse events prior to gross total resection or recurrent glioblastoma
Secondary outcomes (3)
Overall Survival
Progression and response to treatment will be determined using the Response Assessment in Neuro-Oncology (RANO) criteria.
Measured: Every 8 weeks for 24 months
Neurologic function and quality of life
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.
Measured: Every 8 weeks for 24 months
Treatment Toxicity
Quantification of the frequency of adverse events in patients treated with neoadjuvant Pembrolizumab and Temozolomide after gross total resection of recurrent glioblastoma.
Measured: Change in frequency of adverse events after gross total resection or recurrent glioblastoma
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Jan 2023
- Study start1 Nov 2022
- Primary completionJan 2025 (estimated)
- Study completionJan 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for GlioblastomaStudies of the same condition, open and under way.
- More trials run by University of LouisvilleThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- 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.
- Masking
- None (open label)
- Enrolment
- 30 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Louisville
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Donald Miller, University of Louisville
- Investigators
- Donald Miller, MD, Principal investigator, University of Louisville/James Graham Brown Cancer Ctr.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05700955
- Sponsor's protocol ID
- 22.0676
- Status last verified
- Jan 2023
- First submitted
- 28 Sep 2022
- Last updated
- 26 Jan 2023
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 26 Jan 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I Trial of Neoadjuvant Chemoimmunotherapy in Recurrent Glioblastoma
- ClinicalTrials.gov ID
- NCT05700955
- Acronym / sponsor ID
- 22.0676
- Conditions
- Glioblastoma
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 30 participants (estimated)
- Lead sponsor
- University of LouisvilleUniversity, hospital or other
- Study start
- 1 Nov 2022 (actual)
- Primary completion
- Jan 2025 (estimated)
- Study completion
- Jan 2025 (estimated)
- First posted
- 26 Jan 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 2
- 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.
| Arm | Type | Receives |
|---|---|---|
| temozolomide | Experimental | Drug: Pembrolizumab and TemozolomideParticipants will take Temozolomide pills at home at a dose determined by body weight. They will take the pills for five days every 3 weeks. It will be dispensed by the pharmacy and must be stored in a closed container at room temperature, away from heat, moisture, and direct light and kept from freezing. It will be kept out of the reach of children. Outdated medicine or medicine no longer needed will be returned to the Brown Cancer Center pharmacy for disposal. |
| Pembrolizumab | Experimental | Drug: Pembrolizumab and TemozolomidePembrolizumab will be administered at a dose of 200 mg as an IV infusion through a freely flowing IV. The diluted solution will be administered intravenously over 30 minutes through an intravenous line containing a sterile, non-pyrogenic, low-protein binding 0.2 micron to 5 micron in-line or add-on filter. Other drugs will not be co-administered through the same infusion line. Pembrolizumab doses will be repeated every three weeks. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (19 listed)
- -Inclusion Criteria Patients are eligible to be included in the only if they meet all of the following criteria
- Histopathologically proven diagnosis of glioblastoma prior to registration, by pathology report;
- The tumor must be confined to the supratentorial compartment
- The tumor tissue block from the primary diagnosis must be available to be sent for pathology review, after registration.
- History/physical examination within 7 days prior to registration
Key exclusion criteria (16 listed)
- -Exclusion Criteria Patients will be excluded from the study if they meet any of the following criteria
- Previous use of an immunotherapy such as a vaccine therapy, dendritic cell vaccine or intracavitary or convectional enhanced delivery of therapy.
- Prior invasive malignancy (except non-melanomatous skin cancer) within the previous three years
- Severe, active co-morbidity defined as follows:
- Patient must have < 1.5 cm midline shift pre-operative
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Pembrolizumab and TemozolomideAlso: Pembro and TemodarCharacterize the safety and immunologic/genomic/metabolomic effects of neoadjuvant Pembrolizumab and Temozolomide in recurrent glioblastoma. | Drug | Pembrolizumab, temozolomide |
Primary outcome
Treatment toxicity
Time frame: 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.
3 secondary outcomes
Overall Survival
Time frame: Every 8 weeks for 24 months
Neurologic function and quality of life
Time frame: Every 8 weeks for 24 months
Treatment Toxicity
Time frame: Change in frequency of adverse events after gross total resection or recurrent glioblastoma
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Jan 2023.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Donald Miller, MD principal investigator
University of Louisville/James Graham Brown Cancer Ctr.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Pembrolizumab and Temozolomide in people with Glioblastoma, run by University of Louisville at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 19 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 26 Jan 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Donald Miller, MD (502-562-4370, Donald.miller@louisville.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Treatment toxicity (time frame: Change in frequency of adverse events prior to gross total resection or recurrent glioblastoma). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Jan 2023.