GlioblastomaPhase 1PERFORMANCENCT02864368
Peptide Targets for Glioblastoma Against Novel Cytomegalovirus Antigens
A Phase 1 study testing 5-day TMZ, 21-day TMZ and PEP-CMV: Component A in people with Glioblastoma and Glioblastoma Multiforme, run by Eric Thompson, M.D. at 1 site in United States.
Trial summary
Newly diagnosed glioblastoma (GBM) patients with complete or partial surgical resection who were CMV seropositive patients were eligible to enroll on this trial. Patients were enrolled following standard of care chemoradiation and prior to initiation of post-radiation cycles of temozolomide (TMZ) provided they met all… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Glioblastoma, Glioblastoma Multiforme
- What is being tested?
- 5-day TMZ, 21-day TMZ and PEP-CMV: Component A
- Type of treatment
- Vaccines, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 27 participants
- Where
- 1 siteUnited States
- Study dates
- 7 Dec 2016to 15 Jun 2020
- Phase
- Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age ≥ 18 years.
- Histopathologically proven newly-diagnosed primary glioblastoma with complete or partial surgical resection. Biopsy not acceptable.
- Patients must be cytomegalovirus (CMV) seropositive.
- The tumor must be supratentorial.
- Karnofsky performance status of ≥ 70.
- Stable or decreasing steroid dose (≤ 4 mg/day) at time of post-radiation treatment (XRT) adjuvant TMZ initiation. If patients are decreasing steroid use, once they are at 2 mg/day, they may be supplemented with physiologic replacement hydrocortisone therapy (20-30 mg/day in divided doses), at the discretion of the treating oncologist.
- Hematology: absolute neutrophil count (ANC) ≥ 1500 cells/µL, Platelet count ≥ 100,000 cells/µL, Hemoglobin ≥ 9.0 g/dl
- Chemistry: ALT/AST ≤ 3.0 times the upper limit of normal (ULN), Total bilirubin ≤ 1.5 mg x ULN (Exception: Patient has known Gilbert's Syndrome or patient has suspected Gilbert's Syndrome, for which additional lab testing of direct and/or indirect bilirubin supports this diagnosis. In these instances, a total bilirubin of ≤ 3.0 x ULN is acceptable.)
Who cannot join
- Radiographic or cytologic evidence of leptomeningeal or multifocal disease at any time prior to study entry.
- Prior conventional antitumor therapy, other than steroids, RT or TMZ therapy given for glioblastoma.
- Pregnant or need to breast feed during the study period.
- Not adhering to pregnancy prevention recommendations.
- Active infection requiring intravenous antibiotics or an unexplained febrile (> 101.5 F) illness.
- Immunosuppressive disease or human immunodeficiency virus infection.
Show all 11Show fewer
- Patients with unstable or severe intercurrent medical conditions such as severe heart or lung disease.
- Allergic or unable to tolerate TMZ for any reason. Any patient that successfully completed at least 5 weeks of Temodar during standard of care XRT/TMZ and whose blood counts meet the eligibility requirements (inclusion #7) within 4 weeks post XRT/TMZ is eligible.
- Patients with previous inguinal lymph node dissection, radiosurgery, brachytherapy, or radiolabeled monoclonal antibodies.
- Prior allogeneic solid organ transplant.
- Currently receiving or ever received immunosuppressive therapy for an autoimmune disorder or an organ transplant.
Trial locations and contacts
1 site in 1 country.
United States1 site
The Preston Robert Tisch Brain Tumor Center at Duke
Durham, North Carolina, 27710
About this study
Newly diagnosed glioblastoma (GBM) patients with complete or partial surgical resection who were CMV seropositive patients were eligible to enroll on this trial. Patients were enrolled following standard of care chemoradiation and prior to initiation of post-radiation cycles of temozolomide (TMZ) provided they met all eligibility criteria. All eligible patients received a tetanus-diphtheria (Td) vaccination. Patients enrolled on study were randomized to receive either standard TMZ or dose-intensified TMZ (excluding the safety cohort who only received standard TMZ). All patients received a pre-conditioning injection of tetanus on day 22 of the first post-radiation cycle of TMZ. The following day, patients received the first of 3 intradermal (i.d.) injections of the study drug cytomegalovirus peptide (PEP-CMV), which contained either a combination of Component A and Component B or Component A only depending upon when they enrolled on study. Vaccines #2 and #3 will be given at 2 week intervals. Patients who were O[6]-methylguanine-DNA methyltransferase (MGMT) unmethylated received one adjuvant cycle of the TMZ regimen according to their assigned TMZ arm. Patients who were MGMT methylated or whose methylation status was inconclusive continue with up to 12 cycles of TMZ. After the completion of a patient's last TMZ cycle, vaccines continued every 4-6 weeks for a maximum number of 20 vaccines (unless tumor progression occurred). The study ended prematurely due to lack of funds. The preliminary results suggest that the vaccine may be capable of generating an immune response.
Read the detailed description
Patients were enrolled following radiation therapy and prior to initiation of post-radiation therapy cycles of adjuvant TMZ provided they met all eligibility criteria. After signing main consent, patients had immune monitoring blood work collected and received a Tetanus-diphtheria booster vaccination with 0.5 mL of Td (tetanus, diphtheria toxoid, adsorbed). After meeting all eligibility criteria, patients were randomized to receive either standard TMZ (150-200 mg/m^2/day on days 1-5 of each 28-day cycle) with vaccination on Day 23 (-1 day, + 2 days) of each TMZ cycle or to receive dose-intensified TMZ (75-100 mg/m^2/day on days 1-21 of each 28-day cycle) with vaccination on day 23 (-1 day, +2 days) of each TMZ cycle (excluding patients enrolled in the safety cohort who only received standard TMZ).
Patients began their initial cycle of adjuvant TMZ as soon as possible following randomization, if applicable. For Arm 1, the adjuvant TMZ cycle(s) will be given as described above. If a patient had an MGMT unmethylated tumor, they discontinued TMZ after the 1st cycle.
All patients received a tetanus pre-conditioning injection in the right groin on day 22 (+1 day) of cycle 1 of adjuvant TMZ. On the following day, patients receive their study vaccine (either a combination of Component A and Component B or Component A only depending upon when they enrolled on study).
Vaccines #2 and #3 were given at 2 week intervals (+ 3 days), which will resulted in a ~35-day delay before starting TMZ cycle 2. MGMT unmethylated patients did not receive subsequent cycles of TMZ, but continued to receive vaccines approximately every 4 (+2) weeks. Originally, patients received the vaccine as follows: 500 µg of PEP-CMV Component A mixed with Montanide Incomplete Freund's Adjuvant (ISA)-51 intradermally administered in the right groin and 2 hours later, 500 µg of PEP-CMV Component B mixed in 150 µg of Granulocyte Macrophage Colony Stimulating Factor (GM-CSF) intradermally administered in the left groin. A safety cohort was added in 2017 following hypersensitivity reactions in which patient received different schedules of vaccine Components A and B to determine the source of the hypersensitivity reactions. Following this safety cohort, the randomized study was allowed to reinitiate with changes to vaccine administration procedure.
Subsequent revisions were made to the study in the latter part of 2018, due to a continuation of hypersensitivity reactions, and Component B was removed from the study. Patients then received the vaccine as follows: 500 µg of PEP-CMV Component A mixed with Montanide ISA-51 administered intradermally with half in the right groin and half in the left groin.
Patients were imaged with contrast-enhanced magnetic resonance imaging (MRI) within 2 weeks (+3 days) after vaccine 3 and then approximately every 8 weeks. RANO criteria was used for assessment of pseudo-progression, and patients demonstrating definitive progression were removed from study. Blood for immune monitoring was obtained at several time points.
The study ended prematurely due to lack of funds.
- Conditions
- Glioblastoma, Glioblastoma Multiforme
- Being tested
- 5-day TMZ, 21-day TMZ, PEP-CMV: Component A, Tetanus-Diphtheria booster, Tetanus Pre-Conditioning
- Keywords
- PERFORMANCE, Pro00034208, Cytomegalovirus, Ashley
- Medical subject headings
- Glioblastoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
5-day TMZDrug
Also called temozolomide, Temodar
Chemotherapy agent FDA approved to treat newly-diagnosed glioblastoma given as cycles of 150-200 mg/m^2/day on days 1-5 of each 28 day cycle
21-day TMZDrug
Also called temozolomide, Temodar
Chemotherapy agent FDA approved to treat newly-diagnosed glioblastoma given as cycles of dose-intensified TMZ (75-100 mg/m2/day on days 1-21 of each 28 day cycle)
PEP-CMV: Component ABiological
500 µg of PEP-CMV Component A (a synthetic long peptide) mixed with Montanide ISA-51 intradermally administered
Tetanus-Diphtheria boosterDrug
Also called Td, tetanus
At time of enrollment, after signing consent and undergoing immune monitoring blood work, patients will receive Tetanus-diphtheria booster vaccination with 0.5 mL of Td (tetanus, diphtheria toxoid, absorbed)
Tetanus Pre-ConditioningDrug
Also called Td, Tetanus-Diphtheria, tetanus
All patients will receive a tetanus pre-conditioning injection in the right groin intradermally on day 22 (±1 day) of the first post-radiation cycle of TMZ
PEP-CMV: Component BBiological
500 µg of PEP-CMV Component B (a neutralizing antibody epitope from human CMV glycoprotein B conjugated to Keyhole Limpet Hemocyanin) mixed in 150 µg of GM-CSF intradermally administered
| Study group | Role | What they receive |
|---|---|---|
| 5-day TMZ: Components A and B | Experimental | All patients receive Tetanus-Diphtheria booster vaccine at time of enrollment. Cycles of standard TMZ (150-200 mg/m^2/day on days 1-5 of each 28 day cycle) with PEP-CMV vaccination on Day 23 (-1 day, + 2 days) of each TMZ cycle and tetanus pre-conditioning the day before the first vaccine. Receives: Drug: 5-day TMZ; Biological: PEP-CMV: Component A; Drug: Tetanus-Diphtheria booster; Drug: Tetanus Pre-Conditioning; Biological: PEP-CMV: Component B |
| 21-day TMZ: Components A and B | Experimental | All patients receive Tetanus-Diphtheria booster vaccine at time of enrollment. Cycles of dose-intensified TMZ (75-100 mg/m^2/day on days 1-21 of each 28 day cycle) with PEP-CMV vaccination on day 23 (-1 day, + 2 days) of each TMZ cycle and tetanus pre-conditioning the day before the first vaccine. Receives: Drug: 21-day TMZ; Biological: PEP-CMV: Component A; Drug: Tetanus-Diphtheria booster; Drug: Tetanus Pre-Conditioning; Biological: PEP-CMV: Component B |
| 5-day TMZ: Safety Cohort | Experimental | All patients receive Tetanus-Diphtheria booster vaccine at time of enrollment. Cycles of standard TMZ (150-200 mg/m^2/day on days 1-5 of each 28 day cycle) with PEP-CMV vaccination on Day 23 (-1 day, + 2 days) of each TMZ cycle and tetanus pre-conditioning the day before the first vaccine. Vaccine components A and B were administered separately, with a delay between them, to determine if it was an individual component or a combination of the components that resulted in adverse reactions. Receives: Drug: 5-day TMZ; Biological: PEP-CMV: Component A; Drug: Tetanus-Diphtheria booster; Drug: Tetanus Pre-Conditioning; Biological: PEP-CMV: Component B |
| 5-day TMZ: Component A Alone | Experimental | All patients receive Tetanus-Diphtheria booster vaccine at time of enrollment. Cycles of standard TMZ (150-200 mg/m^2/day on days 1-5 of each 28 day cycle) with PEP-CMV vaccination on Day 23 (-1 day, + 2 days) of each TMZ cycle and tetanus pre-conditioning the day before the first vaccine. Receives: Drug: 5-day TMZ; Biological: PEP-CMV: Component A; Drug: Tetanus-Diphtheria booster; Drug: Tetanus Pre-Conditioning |
| 21-day TMZ: Component A Alone | Experimental | All patients receive Tetanus-Diphtheria booster vaccine at time of enrollment. Cycles of dose-intensified TMZ (75-100 mg/m^2/day on days 1-21 of each 28 day cycle) with PEP-CMV vaccination on day 23 (-1 day, + 2 days) of each TMZ cycle and tetanus pre-conditioning the day before the first vaccine. Receives: Drug: 21-day TMZ; Biological: PEP-CMV: Component A; Drug: Tetanus-Diphtheria booster; Drug: Tetanus Pre-Conditioning |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percentage of Participants With Treatment-related Adverse Events
To assess the safety of PEP-CMV vaccination in combination with adjuvant TMZ, the percentage of patients with unacceptable toxicity will be estimated within each arm. All patients who received any PEP-CMV vaccine will be included in these analyses.
Measured: 2 weeks after the 3rd vaccine, which is approximately 12 weeks after consent
Immunologic Response as Measured by Peak Number of T Cells That Secrete IFNγ by ELISPOT in Response to Component A of PEP-CMV
The primary analysis will focus on patients who have follow-up immunologic monitoring after the 3rd vaccination with component A alone and before initiation of the second TMZ/vaccine cycle. Such a patient is considered "evaluable" for the immunologic response primary analyses.
The Wilcoxon rank sum test will compare treatment groups with regard to the median peak number of T cells that secrete IFNγ by ELISPOT in response to component A of PEP-CMV. Analyses will include only those patients who have an assessment of immune response after receiving 3 vaccinations.
Measured: Through study completion, an average of 1.5 years
Secondary outcomes (1)
Antigen Loss
To determine if tumors are CMV antigen negative by immunohistochemical analysis for the presence of the antigen pp65 at the time of disease progression/recurrence
Measured: Through study completion, an average of 1.5 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Aug 2016 (estimated)
- Study start7 Dec 2016
- Primary completion15 Jun 2020
- Study completion15 Jun 2020
Why it stopped: Funding
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for GlioblastomaStudies of the same condition, open and under way.
- 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
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 27 participants (actual)
Sponsor and investigators
- Lead sponsor
- Eric Thompson, M.D.
- Sponsor type
- University, hospital or other
- Collaborators
- Annias Immunotherapeutics, Inc., National Institutes of Health (NIH), National Cancer Institute (NCI)
- Responsible party
- Sponsor-investigator, Eric Thompson, M.D., Duke University
- Investigators
- David Ashley, MBBS, FRACP, PhD, Principal investigator, Duke University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02864368
- Sponsor's protocol ID
- Pro00034208_1
- Other IDs
- 2R42CA153845-02
- Acronym
- PERFORMANCE
- Status last verified
- Jun 2022
- First submitted
- 26 Jul 2016
- Last updated
- 9 Jun 2022
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 9 Jun 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Peptide Targets for Glioblastoma Against Novel Cytomegalovirus Antigens
- ClinicalTrials.gov ID
- NCT02864368
- Acronym / sponsor ID
- PERFORMANCE / Pro00034208_1
- Conditions
- Glioblastoma, Glioblastoma Multiforme
- Keywords
- PERFORMANCE, Pro00034208, Cytomegalovirus, Ashley
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Funding
- Enrolment
- 27 participants (actual)
- Lead sponsor
- Eric Thompson, M.D.University, hospital or other
- Collaborators
- Annias Immunotherapeutics, Inc., National Institutes of Health (NIH), National Cancer Institute (NCI)
- Study start
- 7 Dec 2016 (actual)
- Primary completion
- 15 Jun 2020 (actual)
- Study completion
- 15 Jun 2020 (actual)
- First posted
- 12 Aug 2016 (estimated)
- Results
- Posted 9 Nov 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Newly diagnosed glioblastoma (GBM) patients with complete or partial surgical resection who were CMV seropositive patients were eligible to enroll on this trial. Patients were enrolled following standard of care chemoradiation and prior to initiation of post-radiation cycles of temozolomide (TMZ) provided they met all eligibility criteria. All eligible patients received a tetanus-diphtheria (Td) vaccination. Patients enrolled on study were randomized to receive either standard TMZ or dose-intensified TMZ (excluding the safety cohort who only received standard TMZ). All patients received a pre-conditioning injection of tetanus on day 22 of the first post-radiation cycle of TMZ. The following day, patients received the first of 3 intradermal (i.d.) injections of the study drug cytomegalovirus peptide (PEP-CMV), which contained either a combination of Component A and Component B or Component A only depending upon when they enrolled on study. Vaccines #2 and #3 will be given at 2 week intervals. Patients who were O[6]-methylguanine-DNA methyltransferase (MGMT) unmethylated received one adjuvant cycle of the TMZ regimen according to their assigned TMZ arm. Patients who were MGMT methylated or whose methylation status was inconclusive continue with up to 12 cycles of TMZ. After the completion of a patient's last TMZ cycle, vaccines continued every 4-6 weeks for a maximum number of 20 vaccines (unless tumor progression occurred). The study ended prematurely due to lack of funds. The preliminary results suggest that the vaccine may be capable of generating an immune response.
Detailed description
Patients were enrolled following radiation therapy and prior to initiation of post-radiation therapy cycles of adjuvant TMZ provided they met all eligibility criteria. After signing main consent, patients had immune monitoring blood work collected and received a Tetanus-diphtheria booster vaccination with 0.5 mL of Td (tetanus, diphtheria toxoid, adsorbed). After meeting all eligibility criteria, patients were randomized to receive either standard TMZ (150-200 mg/m^2/day on days 1-5 of each 28-day cycle) with vaccination on Day 23 (-1 day, + 2 days) of each TMZ cycle or to receive dose-intensified TMZ (75-100 mg/m^2/day on days 1-21 of each 28-day cycle) with vaccination on day 23 (-1 day, +2 days) of each TMZ cycle (excluding patients enrolled in the safety cohort who only received standard TMZ).
Patients began their initial cycle of adjuvant TMZ as soon as possible following randomization, if applicable. For Arm 1, the adjuvant TMZ cycle(s) will be given as described above. If a patient had an MGMT unmethylated tumor, they discontinued TMZ after the 1st cycle.
All patients received a tetanus pre-conditioning injection in the right groin on day 22 (+1 day) of cycle 1 of adjuvant TMZ. On the following day, patients receive their study vaccine (either a combination of Component A and Component B or Component A only depending upon when they enrolled on study).
Vaccines #2 and #3 were given at 2 week intervals (+ 3 days), which will resulted in a ~35-day delay before starting TMZ cycle 2. MGMT unmethylated patients did not receive subsequent cycles of TMZ, but continued to receive vaccines approximately every 4 (+2) weeks. Originally, patients received the vaccine as follows: 500 µg of PEP-CMV Component A mixed with Montanide Incomplete Freund's Adjuvant (ISA)-51 intradermally administered in the right groin and 2 hours later, 500 µg of PEP-CMV Component B mixed in 150 µg of Granulocyte Macrophage Colony Stimulating Factor (GM-CSF) intradermally administered in the left groin. A safety cohort was added in 2017 following hypersensitivity reactions in which patient received different schedules of vaccine Components A and B to determine the source of the hypersensitivity reactions. Following this safety cohort, the randomized study was allowed to reinitiate with changes to vaccine administration procedure.
Subsequent revisions were made to the study in the latter part of 2018, due to a continuation of hypersensitivity reactions, and Component B was removed from the study. Patients then received the vaccine as follows: 500 µg of PEP-CMV Component A mixed with Montanide ISA-51 administered intradermally with half in the right groin and half in the left groin.
Patients were imaged with contrast-enhanced magnetic resonance imaging (MRI) within 2 weeks (+3 days) after vaccine 3 and then approximately every 8 weeks. RANO criteria was used for assessment of pseudo-progression, and patients demonstrating definitive progression were removed from study. Blood for immune monitoring was obtained at several time points.
The study ended prematurely due to lack of funds.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 5
| Arm | Type | Receives |
|---|---|---|
| 5-day TMZ: Components A and B | Experimental | Drug: 5-day TMZ, Biological: PEP-CMV: Component A, Drug: Tetanus-Diphtheria booster, Drug: Tetanus Pre-Conditioning, Biological: PEP-CMV: Component BAll patients receive Tetanus-Diphtheria booster vaccine at time of enrollment. Cycles of standard TMZ (150-200 mg/m^2/day on days 1-5 of each 28 day cycle) with PEP-CMV vaccination on Day 23 (-1 day, + 2 days) of each TMZ cycle and tetanus pre-conditioning the day before the first vaccine. |
| 21-day TMZ: Components A and B | Experimental | Drug: 21-day TMZ, Biological: PEP-CMV: Component A, Drug: Tetanus-Diphtheria booster, Drug: Tetanus Pre-Conditioning, Biological: PEP-CMV: Component BAll patients receive Tetanus-Diphtheria booster vaccine at time of enrollment. Cycles of dose-intensified TMZ (75-100 mg/m^2/day on days 1-21 of each 28 day cycle) with PEP-CMV vaccination on day 23 (-1 day, + 2 days) of each TMZ cycle and tetanus pre-conditioning the day before the first vaccine. |
| 5-day TMZ: Safety Cohort | Experimental | Drug: 5-day TMZ, Biological: PEP-CMV: Component A, Drug: Tetanus-Diphtheria booster, Drug: Tetanus Pre-Conditioning, Biological: PEP-CMV: Component BAll patients receive Tetanus-Diphtheria booster vaccine at time of enrollment. Cycles of standard TMZ (150-200 mg/m^2/day on days 1-5 of each 28 day cycle) with PEP-CMV vaccination on Day 23 (-1 day, + 2 days) of each TMZ cycle and tetanus pre-conditioning the day before the first vaccine. Vaccine components A and B were administered separately, with a delay between them, to determine if it was an individual component or a combination of the components that resulted in adverse reactions. |
| 5-day TMZ: Component A Alone | Experimental | Drug: 5-day TMZ, Biological: PEP-CMV: Component A, Drug: Tetanus-Diphtheria booster, Drug: Tetanus Pre-ConditioningAll patients receive Tetanus-Diphtheria booster vaccine at time of enrollment. Cycles of standard TMZ (150-200 mg/m^2/day on days 1-5 of each 28 day cycle) with PEP-CMV vaccination on Day 23 (-1 day, + 2 days) of each TMZ cycle and tetanus pre-conditioning the day before the first vaccine. |
| 21-day TMZ: Component A Alone | Experimental | Drug: 21-day TMZ, Biological: PEP-CMV: Component A, Drug: Tetanus-Diphtheria booster, Drug: Tetanus Pre-ConditioningAll patients receive Tetanus-Diphtheria booster vaccine at time of enrollment. Cycles of dose-intensified TMZ (75-100 mg/m^2/day on days 1-21 of each 28 day cycle) with PEP-CMV vaccination on day 23 (-1 day, + 2 days) of each TMZ cycle and tetanus pre-conditioning the day before the first vaccine. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Age ≥ 18 years.
- Histopathologically proven newly-diagnosed primary glioblastoma with complete or partial surgical resection. Biopsy not acceptable.
- Patients must be cytomegalovirus (CMV) seropositive.
- The tumor must be supratentorial.
- Karnofsky performance status of ≥ 70.
Key exclusion criteria (11 listed)
- Radiographic or cytologic evidence of leptomeningeal or multifocal disease at any time prior to study entry.
- Prior conventional antitumor therapy, other than steroids, RT or TMZ therapy given for glioblastoma.
- Pregnant or need to breast feed during the study period.
- Not adhering to pregnancy prevention recommendations.
- Active infection requiring intravenous antibiotics or an unexplained febrile (> 101.5 F) illness.
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 |
|---|---|---|
| 5-day TMZAlso: temozolomide, TemodarChemotherapy agent FDA approved to treat newly-diagnosed glioblastoma given as cycles of 150-200 mg/m^2/day on days 1-5 of each 28 day cycle | Drug | 5-day TMZ: Component A Alone, 5-day TMZ: Components A and B, 5-day TMZ: Safety Cohort |
| 21-day TMZAlso: temozolomide, TemodarChemotherapy agent FDA approved to treat newly-diagnosed glioblastoma given as cycles of dose-intensified TMZ (75-100 mg/m2/day on days 1-21 of each 28 day cycle) | Drug | 21-day TMZ: Component A Alone, 21-day TMZ: Components A and B |
| PEP-CMV: Component A500 µg of PEP-CMV Component A (a synthetic long peptide) mixed with Montanide ISA-51 intradermally administered | Biological | 21-day TMZ: Component A Alone, 21-day TMZ: Components A and B, 5-day TMZ: Component A Alone, 5-day TMZ: Components A and B, 5-day TMZ: Safety Cohort |
| Tetanus-Diphtheria boosterAlso: Td, tetanusAt time of enrollment, after signing consent and undergoing immune monitoring blood work, patients will receive Tetanus-diphtheria booster vaccination with 0.5 mL of Td (tetanus, diphtheria toxoid, absorbed) | Drug | 21-day TMZ: Component A Alone, 21-day TMZ: Components A and B, 5-day TMZ: Component A Alone, 5-day TMZ: Components A and B, 5-day TMZ: Safety Cohort |
| Tetanus Pre-ConditioningAlso: Td, Tetanus-Diphtheria, tetanusAll patients will receive a tetanus pre-conditioning injection in the right groin intradermally on day 22 (±1 day) of the first post-radiation cycle of TMZ | Drug | 21-day TMZ: Component A Alone, 21-day TMZ: Components A and B, 5-day TMZ: Component A Alone, 5-day TMZ: Components A and B, 5-day TMZ: Safety Cohort |
| PEP-CMV: Component B500 µg of PEP-CMV Component B (a neutralizing antibody epitope from human CMV glycoprotein B conjugated to Keyhole Limpet Hemocyanin) mixed in 150 µg of GM-CSF intradermally administered | Biological | 21-day TMZ: Components A and B, 5-day TMZ: Components A and B, 5-day TMZ: Safety Cohort |
Primary outcome
Percentage of Participants With Treatment-related Adverse Events
Time frame: 2 weeks after the 3rd vaccine, which is approximately 12 weeks after consent
To assess the safety of PEP-CMV vaccination in combination with adjuvant TMZ, the percentage of patients with unacceptable toxicity will be estimated within each arm. All patients who received any PEP-CMV vaccine will be included in these analyses.
Immunologic Response as Measured by Peak Number of T Cells That Secrete IFNγ by ELISPOT in Response to Component A of PEP-CMV
Time frame: Through study completion, an average of 1.5 years
The primary analysis will focus on patients who have follow-up immunologic monitoring after the 3rd vaccination with component A alone and before initiation of the second TMZ/vaccine cycle. Such a patient is considered "evaluable" for the immunologic response primary analyses. The Wilcoxon rank sum test will compare treatment groups with regard to the median peak number of T cells that secrete IFNγ by ELISPOT in response to component A of PEP-CMV. Analyses will include only those patients who have an assessment of immune response after receiving 3 vaccinations.
1 secondary outcome
Antigen Loss
Time frame: Through study completion, an average of 1.5 years
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Jun 2022.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- The Preston Robert Tisch Brain Tumor Center at DukeLink provided by the sponsor.
- Duke Cancer InstituteLink provided by the sponsor.
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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.
David Ashley, MBBS, FRACP, PhD principal investigator
Duke University
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 5-day TMZ, 21-day TMZ and PEP-CMV: Component A in people with Glioblastoma and Glioblastoma Multiforme, run by Eric Thompson, M.D. 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 8 inclusion and 11 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: stopped early, as of the sponsor's last update on 9 Jun 2022. 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?
Yes. Results are posted in the registry (first posted 9 Nov 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Percentage of Participants With Treatment-related Adverse Events (time frame: 2 weeks after the 3rd vaccine, which is approximately 12 weeks after consent). The study lists 2 primary outcomes in all. 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 9 Jun 2022.