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| ID | Type | Description | Link |
|---|---|---|---|
| 17-C-0034 |
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Study closed early due to poor accrual.
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Background:
Glioblastoma (GBM) refers to a specific kind of brain cancer called glioblastoma. The standard treatment for GBM is radiation plus temozolomide, an oral chemotherapy drug. Pembrolizumab is an immune therapy that is now used to treat other cancers. The addition of pembrolizumab to the standard treatment of radiation and temozolomide has been shown to be well tolerated. Researchers want to see if adding a vaccine made from the person's own tumor will improve the effect of the pembrolizumab. The vaccine which is developed from fresh tumor taken at the time of surgery is called heat shock protein peptide complex-96 (HSPPC-96).
Objectives:
To see if the adding of pembrolizumab and HSPPC-96 improves the standard treatment for glioblastoma.
Eligibility:
Adults at least 18 years old with glioblastoma.
Design:
Participants will be screened with typical cancer tests:
Brain scan
Medical history
Blood and urine tests
Questions about quality of life and symptoms
These tests will be repeated throughout the study.
Participants will have surgery to remove their tumor. A tissue sample from the tumor will be sent to a lab. A vaccine will be made from it.
Some participants will get pembrolizumab and vaccine. Some will get pembrolizumab and placebo. Participants will not know which they get.
Participants will get radiation for 6 weeks.
Participants will take temozolomide by mouth before each treatment.
Participants will get pembrolizumab by intravenous (IV) for 30 minutes 3 times over the radiation cycle.
Participants will keep taking the 2 drugs every few weeks for about a year. Some may take pembrolizumab for an additional year.
Most participants will get the vaccine or placebo after radiation. They will get it 5 times over 6 weeks. Some participants will continue to get the vaccine every few weeks for 1 or 2 years.
Participants will repeat the screening tests when they stop study treatment. They will also have follow-up phone calls.
Background:
Eligibility:
Objective:
- The primary endpoint is to determine whether the one-year overall survival (OS) rate is improved in newly diagnosed GBM patients whose tumors have an unmethylated MGMT promoter and are IDH wildtype treated with radiation therapy (RT) + temozolomide (TMZ) + Pembrolizumab followed by TMZ + Pembrolizumab + HSPPC-96 vaccine or Placebo vaccine x 6 cycles (1 cycle is 9 weeks).
Design:
This will be a randomized, double blind phase II trial of surgery, RT + TMZ + Pembrolizumab followed by TMZ + Pembrolizumab +/- HSPPC-96 in newly diagnosed GBM patients whose tumors have an unmethylated MGMT promoter and are IDH wildtype.
Subjects will be assigned to intervention based on ability to generate vaccine as follows:
If >= 80 % of tumor removed, >=7 g of tumor is resected but HSPPC-96 cannot be generated, subjects will be treated on the ancillary arm of RT+TMZ +Pembrolizumab followed by TMZ+ Pembrolizumab.
If>= 80% of contrasting enhanced tumor removed (based on T1 Post contrast magnetic resonance imaging (MRI) using cross sectional measurement), >= 7 g of tumor is resected and sufficient HSPPC-96 is generated, subjects will be included in the main cohort and will be randomized on a 1:1 basis to receive:
OR
--- RT+TMZ +Pembrolizumab followed by TMZ+Pembrolizumab+HSPPC-96
-Subjects whose tumor does not meet the criteria (unmethylated MGMT promoter and IDH wildtype by pathology) and for whom < 80 % of tumor is removed or < 7g of tumor is resected are not eligible for further intervention. Approximately 8 potentially eligible patients are screened per month, and it is anticipated that at least 1-2 per month will be accrued per site.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 1/Temozolomide + Pembrolizumab + Radiation Therapy | Other | Standard treatment with experimental treatment (pembro) added. |
|
| 2/Temozolomide+Pembrolizumab | Experimental | Temozolomide+Pembrolizumab |
|
| 3/Temozolomide+Pembrolizumab+ Heat Shock Protein Peptide Complex-96 (HSPPC-96) Vaccine | Experimental | Temozolomide+Pembrolizumab+ HSPPC96 Vaccine |
|
| 4/Temozolomide+Pembrolizumab+ Placebo | Placebo Comparator | Temozolomide+Pembrolizumab+ Placebo |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Pembrolizumab | Drug | Pembrolizumab at 200mg will be administered on day 1 as a 30-minute intravenous (IV) infusion (prior to radiation therapy (RT) every 3 weeks during RT on days 1, 22 and 43. At one year, if participants are doing well, they may continue pembrolizumab for 12 more months alone or in conjunction with heat shock protein peptide complex -96 (HSPPC 96) or placebo vaccine if any is available. |
| Measure | Description | Time Frame |
|---|---|---|
| One-year Overall Survival (OS) Rate | One-year overall survival (OS) rate is defined as the percentage of participants who from time of registration survived to one year in newly diagnosed O6-methylguanine-deoxyribonucleic acid (DNA) methyltransferase (MGMT) unmethylated Glioblastoma (GBM) participants treated with radiation therapy (RT) + Temozolomide (TMZ) + Pembrolizumab followed by Pembrolizumab + TMZ +/- heat-shock protein peptide complex-96 (HSPPC-96) x 6 cycles (1 cycle is 9 weeks) months. Rate of OS is measured by Kaplan-Meier method. | One year |
| Measure | Description | Time Frame |
|---|---|---|
| Response Rate | Response was determined by the Response Assessment in Neuro-Oncology Criteria (RANO) criteria and reported with 95% confidence intervals using exact binomial probability distributions. Complete response is no T1 gadolinium enhancing disease or stable or decreasing T2/fluid-attenuated inversion recovery (FLAIR). Partial response is ≥ 50% decrease in T1 gadolinium enhancing disease or stable or decreasing T2/FLAIR. Stable disease is <50% decrease but <25% increase in T1 gadolinium enhancing disease or stable or decreasing T2/FLAIR. Progressive disease is ≥25% incT1 gadolinium enhancing disease, appearance of new lesions or increase in T2/FLAIR. |
| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants With Serious and/or Non-serious Adverse Events Assessed by the Common Terminology Criteria for Adverse Events (CTCAE v5.0) | Here is the number of participants with serious and/or non-serious adverse events assessed by the Common Terminology Criteria for Adverse Events (CTCAE v5.0). A non-serious adverse event is any untoward medical occurrence. A serious adverse event is an adverse event or suspected adverse reaction that results in death, a life-threatening adverse drug experience, hospitalization, disruption of the ability to conduct normal life functions, congenital anomaly/birth defect or important medical events that jeopardize the patient or subject and may require medical or surgical intervention to prevent one of the previous outcomes mentioned. |
Pre-Surgery (Step 1) Inclusion:
Post-Surgery (Step 2) Inclusion:
Pathology must be a GBM, O6-methylguanine-deoxyribonucleic acid (DNA) methyltransferase (MGMT) promoter region determined to be unmethylated and isocitrate Dehydrogenase (IDH) wild type greater than or equal to 80 % resection of contrast enhanced tumor on post operative MRI and greater than 7 grams of tumor resected are required otherwise patient is ineligible.
Treatment must be initiated greater than or equal to 14 days and < 6 weeks from surgery.
Craniotomy site must be adequately healed and free of drainage or cellulitis, and the underlying cranioplasty must appear intact at the time of radiation. Radiation must start within 6 weeks of surgery.
Dexamethasone dose should be less than or equal to 4 mg/day or steroid equivalent prior to starting treatment. If higher doses are needed, consult with Study Chair.
Female subjects of childbearing potential should have a negative urine or serum pregnancy within 7 days prior to receiving the first dose of study medication. If the urine test is positive or cannot be confirmed as negative, a negative serum pregnancy test will be required.
Patients must have adequate organ and bone marrow function within 14 days prior to step 2 registration, as defined below:
Females of child-bearing potential (FOCBP) and males must agree to use two adequate contraception methods (give examples, e.g., hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation, and for 120 days following completion of therapy. Should a female patient become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately. Male patients who father a child should notify the treating physician.
NOTE: A FOCBP is any woman (regardless of sexual orientation, having undergone a tubal ligation, or remaining celibate by choice) who meets the following criteria:
Has not undergone a hysterectomy or bilateral oophorectomy
Has had menses at any time in the preceding 12 consecutive months (and therefore has not been naturally postmenopausal for > 12 months)
EXCLUSION CRITERIA:
Pre-Surgery (Step 1) Exclusion:
Known history of immunodeficiency (HIV). This medical entity can be exacerbated by programmed cell death protein 1 (PD-1) blockade.
History of another malignancy in the previous 3 years, with a disease-free interval of < 3 years. Exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or in situ cervical cancer that has undergone potentially curative therapy. Patients who have undergone a bone marrow or stem-cell transplant for any malignancy are excluded.
Has an active autoimmune disease requiring systemic treatment within the past 3 months or a documented history of clinically severe autoimmune disease, or a syndrome that requires chronic systemic steroids or immunosuppressive agents except as noted above. Subjects with vitiligo or resolved childhood asthma/atopy would be an exception to this rule. Subjects that require intermittent use of bronchodilators or local steroid injections will not be excluded from the study. Subjects with hypothyroidism stable on hormone replacement or Sjorgren's syndrome will not be excluded from the study.
Has a history of interstitial lung disease, non-infectious pneumonitis, or pneumonitis.
Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject's participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator. Examples include:
Is pregnant or breastfeeding or expecting to conceive or father children within the projected duration of the trial, starting with the pre-screening or screening visit through 120 days after the last dose of trial treatment.
The effects of pembrolizumab and HSPPC-96 on the developing human fetus are unknown. For this reason and because checkpoint inhibitors and immunotherapeutic vaccines as well as other therapeutic agents used in this trial are known to be teratogenic, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately.
Has received prior therapy with an anti-PD-1, anti-programmed death-ligand 1 (PD-L1), anti-PD-L2, anti-4-1BB (CD137), or anti-Cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) antibody (including ipilimumab or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways).
On treatment for Hepatitis B or Hepatitis C or history of tuberculosis (TB).
Patients who have a history of allergic reactions attributed to compounds of similar chemical or biologic composition to Pembrolizumab are not eligible. Known hypersensitivity to any excipients of Pembrolizumab.
Post-Surgery (Step 2) Exclusion:
Patients are ineligible if the tumor is not a GBM, MGMT promoter region determined to be unmethylated and IDH wild type, or if < 80 % resection of contrast enhanced tumor on post-operative MRI or < 7 grams of tumor is resected.
Patients who are receiving any other investigational agents.
Known history of immunodeficiency (HIV). This medical entity can be exacerbated by PD-1 blockade.
Any form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment excluding steroids. Attempts should be made to have patient on lowest possible dose of steroids. These medical entities can be exacerbated by PD-1 blockade.
History of another malignancy in the previous 3 years, with a disease-free interval of < 3 years. Exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or in situ cervical cancer that has undergone potentially curative therapy. Patients who have undergone a bone marrow or stem-cell transplant for any malignancy are excluded.
Has an active autoimmune disease requiring systemic treatment within the past 3 months or a documented history of clinically severe autoimmune disease, or a syndrome that requires chronic systemic steroids or immunosuppressive agents except as noted above. Subjects with vitiligo or resolved childhood asthma/atopy would be an exception to this rule. Subjects that require intermittent use of bronchodilators or local steroid injections will not be excluded from the study. Subjects with hypothyroidism stable on hormone replacement or Sjorgen's syndrome will not be excluded from the study.
Has a history of interstitial lung disease, non-infectious pneumonitis, or pneumonitis.
Has an active infection requiring systemic antibiotics within 10 days of surgery.
Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject's participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator. Examples include:
Is pregnant or breastfeeding or expecting to conceive or father children within the projected duration of the trial, starting with the pre-screening or screening visit through 120 days after the last dose of trial treatment.
The effects of pembrolizumab and HSPPC-96 on the developing human fetus are unknown. For this reason and because checkpoint inhibitors and immunotherapeutic vaccines as well as other therapeutic agents used in this trial are known to be teratogenic, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately.
Has received prior therapy with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or anti- Cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) antibody (including ipilimumab or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways).
On treatment for Hepatitis B or Hepatitis C or history of TB.
Has received a live vaccine within 30 days prior to the first dose of trial treatment
Patients who have a history of allergic reactions attributed to compounds of similar chemical or biologic composition to Pembrolizumab are not eligible. Known hypersensitivity to any excipients of Pembrolizumab.
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| Name | Affiliation | Role |
|---|---|---|
| Kevin Camphausen, M.D. | National Cancer Institute (NCI) | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| National Institutes of Health Clinical Center | Bethesda | Maryland | 20892 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 42396282 | Derived | Ozer BH, Lindhorst SM, Merrell RT, Trevino CR, Rudnick JD, Avgeropoulos NG, Ramakrishna N, Khagi S, Rauf Y, Walbert T, Pan E, Youssef M, Fink KL, Mandel JJ, Taylor LP, Colman H, Dunbar EM, Paleologos N, Burton EC, Wu J, Leeper HE, Gonzalez J, Penas-Prado M, Raizer JJ, Veglia E, Craig S, Yuan Y, Chambers C, Wall K, Grajkowska E, Mendoza T, Armstrong TS, Gilbert MR. Pembrolizumab, Temozolomide and HSPPC-96 Vaccine in Newly Diagnosed Glioblastoma Post-Chemoradiation: Results from a Multi-institutional, Phase 2, Randomized, Placebo-Controlled Trial. medRxiv [Preprint]. 2026 Jun 24:2026.06.22.26354817. doi: 10.64898/2026.06.22.26354817. |
| Label | URL |
|---|---|
| NIH Clinical Center Detailed Web Page | View source |
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All individual participant data (IPD) recorded in the medical record will be shared with intramural investigators upon request. In addition, all large-scale genomic sequencing data will be shared with subscribers to the database of Genotypes and Phenotypes (dbGaP). All collected IPD will be shared with collaborators under the terms of collaborative agreements.
Clinical data available during the study and indefinitely. Genomic data are available once genomic data are uploaded per protocol Genomic Data Sharing (GDS) plan for as long as database is active. All collected individual participant data (IPD) will be available after primary analysis has been published.
Clinical data will be made available via subscription to Biomedical Translational Research Information System (BTRIS) and with the permission of the study principal investigator (PI). Genomic data are made available via the database of Genotypes and Phenotypes (dbGaP) through requests to the data custodians.
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| ID | Title | Description |
|---|---|---|
| FG000 | Vaccine | Radiation therapy (RT)+Temozolomide (TZ)+Pembrolizumab+Heat Shock Protein Peptide Complex-96.(HSPPC-96). Pembrolizumab at 200mg will be administered on day 1 as a 30-minute intravenous (IV) infusion (prior to radiation therapy during RT phase) every 3 weeks on days 1, 22 and 43. Post RT, participants continue on Pembrolizumab 200mg on day 1 as a 30-minute IV infusion every 3 weeks on days 1, 22, and 43. At one year, if participants are doing well, they may continue pembrolizumab for 12 more months alone or in conjunction with HSPPC-96 vaccine if any is available. One week post RT, patients will receive weekly x 4 a dose of HSPPC-96 0.4mL intradermal vaccine. HSPPC-96 vaccine will then be given 21 days after the day 5 dose of temozolomide. HSPPC-96 vaccine will be given for 6 cycles or until supply runs out. At one year, if patients are doing well, they may continue pembrolizumab for 12 more months alone or in conjunction with HSPPC-96 if any is available. Temozolomide: TMZ will be administered on day 1 of radiation therapy (before RT treatment) and continue throughout RT at the dose of 75 mg/m^2. Post RT: The starting TMZ dose will be 150 mg/m^2/day for cycle 1, days 1-5, with a single dose escalation to 200 mg/m^2/day (days 29-33) and for all subsequent treatment if no treatment-related adverse events greater than Grade 2 are noted. TMZ will be given for 6 cycles. |
| FG001 | Placebo | Radiation therapy (RT)+Temozolomide (TZ)+Pembrolizumab+Placebo Vaccine. Pembrolizumab at 200mg will be administered on day 1 as a 30-minute intravenous (IV) infusion (prior to radiation therapy during RT phase) every 3 weeks on days 1, 22 and 43. Post RT, participants continue on Pembrolizumab 200mg on day 1 as a 30-minute IV infusion every 3 weeks on days 1, 22, and 43. At one year, if participants are doing well, they may continue pembrolizumab for 12 more months alone or in conjunction with placebo vaccine if any is available. One week post RT, patients will receive weekly x 4 a dose of placebo vaccine. Placebo vaccine will then be given 21 days after the day 5 dose of temozolomide. Placebo vaccine will be given for 6 cycles or until supply runs out. Participants who receive placebo will be matched for number of vaccine injections that were generated by their tumor tissue. At one year, if patients are doing well, they may continue pembrolizumab for 12 more months alone or in conjunction with placebo vaccine if any is available. Temozolomide: TMZ will be administered on day 1 of radiation therapy (before RT treatment) and continue throughout RT at the dose of 75 mg/m^2. Post RT: The starting TMZ dose will be 150 mg/m^2/day for cycle 1, days 1-5, with a single dose escalation to 200 mg/m^2/day (days 29-33) and for all subsequent treatment if no treatment-related adverse events greater than Grade 2 are noted. TMZ will be given for 6 cycles. |
| FG002 | Ancillary Treatment | Radiation therapy (RT) + Temozolomide (TMZ) + Pembrolizumab. Pembrolizumab at 200mg will be administered on day 1 as a 30-minute intravenous (IV) infusion (prior to radiation therapy during RT phase) every 3 weeks on days 1, 22 and 43. Post RT, participants continue on Pembrolizumab 200mg on day 1 as 30-minute IV infusion every 3 weeks on days 1, 22, and 43. After completion of 6 cycles, participants may continue on Pembrolizumab for an additional 12 months if felt to be of benefit by the treating physician. Temozolomide: TMZ will be administered on day 1 of radiation therapy (before RT treatment) and continue throughout RT at the dose of 75 mg/m^2. Post RT: The starting TMZ dose will be 150 mg/m^2/day for cycle 1, days 1-5, with a single dose escalation to 200 mg/m^2/day (days 29-33) and for all subsequent treatment if no treatment-related adverse events greater than Grade 2 are noted. TMZ will be given for 6 cycles. |
| FG003 | Enrolled But Not Treated | Participants were enrolled but not treated. |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Vaccine | Radiation therapy (RT)+Temozolomide (TZ)+Pembrolizumab+Heat Shock Protein Peptide Complex-96.(HSPPC-96). Pembrolizumab at 200mg will be administered on day 1 as a 30-minute intravenous (IV) infusion (prior to radiation therapy during RT phase) every 3 weeks on days 1, 22 and 43. Post RT, participants continue on Pembrolizumab 200mg on day 1 as a 30-minute IV infusion every 3 weeks on days 1, 22, and 43. At one year, if participants are doing well, they may continue pembrolizumab for 12 more months alone or in conjunction with HSPPC-96 vaccine if any is available. One week post RT, patients will receive weekly x 4 a dose of HSPPC-96 0.4mL intradermal vaccine. HSPPC-96 vaccine will then be given 21 days after the day 5 dose of temozolomide. HSPPC-96 vaccine will be given for 6 cycles or until supply runs out. At one year, if patients are doing well, they may continue pembrolizumab for 12 more months alone or in conjunction with HSPPC-96 if any is available. Temozolomide: TMZ will be administered on day 1 of radiation therapy (before RT treatment) and continue throughout RT at the dose of 75 mg/m^2. Post RT: The starting TMZ dose will be 150 mg/m^2/day for cycle 1, days 1-5, with a single dose escalation to 200 mg/m^2/day (days 29-33) and for all subsequent treatment if no treatment-related adverse events greater than Grade 2 are noted. TMZ will be given for 6 cycles. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | One-year Overall Survival (OS) Rate | One-year overall survival (OS) rate is defined as the percentage of participants who from time of registration survived to one year in newly diagnosed O6-methylguanine-deoxyribonucleic acid (DNA) methyltransferase (MGMT) unmethylated Glioblastoma (GBM) participants treated with radiation therapy (RT) + Temozolomide (TMZ) + Pembrolizumab followed by Pembrolizumab + TMZ +/- heat-shock protein peptide complex-96 (HSPPC-96) x 6 cycles (1 cycle is 9 weeks) months. Rate of OS is measured by Kaplan-Meier method. | Posted | Number | 95% Confidence Interval | percentage of participants | One year |
|
Date treatment consent signed to date off study, approximately 61.5 months.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Vaccine | Radiation therapy (RT)+Temozolomide (TZ)+Pembrolizumab+Heat Shock Protein Peptide Complex-96.(HSPPC-96). Pembrolizumab at 200mg will be administered on day 1 as a 30-minute intravenous (IV) infusion (prior to radiation therapy during RT phase) every 3 weeks on days 1, 22 and 43. Post RT, participants continue on Pembrolizumab 200mg on day 1 as a 30-minute IV infusion every 3 weeks on days 1, 22, and 43. At one year, if participants are doing well, they may continue pembrolizumab for 12 more months alone or in conjunction with HSPPC-96 vaccine if any is available. One week post RT, patients will receive weekly x 4 a dose of HSPPC-96 0.4mL intradermal vaccine. HSPPC-96 vaccine will then be given 21 days after the day 5 dose of temozolomide. HSPPC-96 vaccine will be given for 6 cycles or until supply runs out. At one year, if patients are doing well, they may continue pembrolizumab for 12 more months alone or in conjunction with HSPPC-96 if any is available. Temozolomide: TMZ will be administered on day 1 of radiation therapy (before RT treatment) and continue throughout RT at the dose of 75 mg/m^2. Post RT: The starting TMZ dose will be 150 mg/m^2/day for cycle 1, days 1-5, with a single dose escalation to 200 mg/m^2/day (days 29-33) and for all subsequent treatment if no treatment-related adverse events greater than Grade 2 are noted. TMZ will be given for 6 cycles. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Alanine aminotransferase increased | Investigations | CTCAE (5.0) | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Abdominal pain | Gastrointestinal disorders | CTCAE (5.0) | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Kevin Camphausen | National Cancer Institute | 240-760-6205 | camphauk@mail.nih.gov |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Jun 25, 2025 | Jul 30, 2025 | Prot_SAP_003.pdf |
| ICF | No | No | Yes | Informed Consent Form | Aug 24, 2021 | Oct 4, 2023 | ICF_001.pdf |
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| ID | Term |
|---|---|
| D005909 | Glioblastoma |
| D005910 | Glioma |
| ID | Term |
|---|---|
| D001254 | Astrocytoma |
| D018302 | Neoplasms, Neuroepithelial |
| D017599 | Neuroectodermal Tumors |
| D009373 | Neoplasms, Germ Cell and Embryonal |
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| ID | Term |
|---|---|
| C582435 | pembrolizumab |
| C484813 | vitespin |
| D000077204 | Temozolomide |
| D013514 | Surgical Procedures, Operative |
| ID | Term |
|---|---|
| D003606 | Dacarbazine |
| D014226 | Triazenes |
| D009930 | Organic Chemicals |
| D007093 | Imidazoles |
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|
|
| HSPPC-96 | Biological | One week post RT, patients will receive weekly x 4 a dose of heat shock protein peptide complex -96 (HSPPC 96) 0.4mL intradermal vaccine or placebo. HSPPC-96 vaccine or placebo will then be given 21 days after the day 5 dose of temozolomide (TMZ). HSPPC-96 vaccine or placebo vaccine will be given for 6 cycles or until supply runs out. Participants who receive placebo will be matched for number of vaccine injections that were generated by their tumor tissue. At one year, if participants are doing well, they may continue pembrolizumab for 12 more months alone or in conjunction with HSPPC-96 or placebo vaccine if any is available. |
|
|
| Temozolomide | Drug | Temozolomide (TMZ) will be administered on day 1 of radiation therapy (before radiation therapy (RT) treatment) and continue throughout RT at the dose of 75 mg/m^2. Post RT: The starting TMZ dose will be 150 mg/m^2/day for cycle 1, days 1-5, with a single dose escalation to 200 mg/m^2/day (days 29-33) and for all subsequent treatment if no treatment-related adverse events greater than Grade 2 are noted. TMZ will be given for 6 cycles. |
|
|
| Placebo | Other | One week post radiation therapy (RT), participants will receive weekly x 4 a dose of heat shock protein peptide complex -96 (HSPPC 96) 0.4mL intradermal vaccine or placebo. HSPPC-96 vaccine or placebo will then be given 21 days after the day 5 dose of Temozolomide (TMZ). HSPPC-96 vaccine or placebo vaccine will be given for 6 cycles or until supply runs out. Participants who receive placebo will be matched for number of vaccine injections that were generated by their tumor tissue. At one year, if participants are doing well, they may continue pembrolizumab for 12 more months alone or in conjunction with HSPPC-96 or placebo vaccine if any is available. |
|
| Surgery | Procedure | Tissue for vaccine production and neo-epitope monitoring. |
|
| After treatment, up to 26 months |
| Overall Survival (OS) | OS is defined as the time from registration to the time of death. Kaplan-Meier curves will be used to analyze overall survival. | Time from registration to the time of death or off study up to 26 months |
| Overall Survival at 6, 12 and 24 Months, Post-registration | Participants who are alive at 6, 12 and 24 months, post-registration determined from the level of the Kaplan-Meier curves at these time points. | 6, 12 and 24 months, post-registration |
| Vaccine Cohort: Number of Adverse Events Grades 2-5, Unrelated, Unlikely, Possibly, Probably, and/or Definitely Related to Pembrolizumab | Adverse events were assessed by the Common Terminology Criteria for Adverse Events (CTCAE v5.0). Grade 2 is moderate. Grade 3 is severe. Grade 4 is life-threatening. And Grade 5 is death related to adverse event. | Start of treatment until participant is off study, approximately 61.5 months |
| Placebo Cohort: Number of Adverse Events Grades 2-5, Unrelated, Unlikely, Possibly, Probably, and/or Definitely Related to Pembrolizumab | Adverse events were assessed by the Common Terminology Criteria for Adverse Events (CTCAE v5.0). Grade 2 is moderate. Grade 3 is severe. Grade 4 is life-threatening. And Grade 5 is death related to adverse event. | Start of treatment until participant is off study, approximately 61.5 months |
| Ancillary Treatment Cohort: Number of Adverse Events Grades 2-5, Unrelated, Unlikely, Possibly, Probably, and/or Definitely Related to Pembrolizumab | Adverse events were assessed by the Common Terminology Criteria for Adverse Events (CTCAE v5.0). Grade 2 is moderate. Grade 3 is severe. Grade 4 is life-threatening. And Grade 5 is death related to adverse event. | Start of treatment until participant is off study, approximately 61.5 months |
| Mean Symptom Severity Using the MD Anderson Symptom Inventory-Brain Tumor Module (MDASI-BT). | To evaluate the occurrence of symptoms and correlate to disease progression and tolerance to treatment using the MD Anderson Symptom Inventory-Brain Tumor Module (MDASI-BT). Participants rate their symptoms on a questionnaire using an 11-point scale (0-10). 0 is "not present" and 10 is "as bad as you can imagine." Differences of at least 2 points will be classified as the minimum clinically meaningful change in the symptom severity measures. Higher score indicates worse severity. | Baseline, end of treatment or discontinuation, and 30 days after last dose |
| Mean Symptom Interference Using the MD Anderson Symptom Inventory-Brain Tumor Module (MDASI-BT). | To evaluate the occurrence of symptoms and correlate to disease progression and tolerance to treatment using the MD Anderson Symptom Inventory-Brain Tumor Module (MDASI-BT). Participants rate their symptoms on a questionnaire using an 11-point scale (0-10) of how much symptoms interfered with different aspects of a patient's life in the last 24 hours such as general activity, mood, work, relations with other people, walking and enjoyment of life. 0 is "not present" and 10 is "as bad as you can imagine." Differences of at least 2 points will be classified as the minimum clinically meaningful change in the symptom severity measures. | Baseline, end of treatment or discontinuation, and 30 days after last dose |
| Percentage of Participants Rating Their Symptom Severity to Be 5 or Greater (on a 0-10) Scale Using the MD Anderson Symptom Inventory-Brain Tumor Module (MDASI-BT) | Percentage of participants rating their symptom severity to be 5 or greater (on a 0-10) scale using the MD Anderson Symptom Inventory-Brain Tumor Module (MDASI-BT). Participants rate their symptoms on a questionnaire using an 11-point scale (0-10). 0 is "not present" and 10 is "as bad as you can imagine." | Baseline, end of treatment or discontinuation, and 30 days after last dose |
| Progression Free Survival (PFS) | PFS is defined as the time from registration to the time of confirmed progression. Progression was measured by the immunotherapy response assessment for neuro-oncology (iRANO) criteria. Progressive disease is ≥25% increase in the sum of bi-perpendicular diameters of enhancing disease or new lesions or significant worsened T2/fluid-attenuated inversion recovery (FLAIR) or significant clinical decline. | Time from registration to the time of confirmed progression, an average of 9 months |
| Date treatment consent signed to date off study, approximately 61.5 months. |
| Participant withdrew consent. |
|
| Switched to alternative treatment. |
|
| Participant withdrew consent for personal reasons. |
|
| Screen failures |
|
| Chose treatment outside of UNC |
|
| Unable to comply with protocol requirements |
|
| Participant declined to participate (before treatment started) |
|
| Physician Decision |
|
| BG001 | Placebo | Radiation therapy (RT)+Temozolomide (TZ)+Pembrolizumab+Placebo Vaccine. Pembrolizumab at 200mg will be administered on day 1 as a 30-minute intravenous (IV) infusion (prior to radiation therapy during RT phase) every 3 weeks on days 1, 22 and 43. Post RT, participants continue on Pembrolizumab 200mg on day 1 as a 30-minute IV infusion every 3 weeks on days 1, 22, and 43. At one year, if participants are doing well, they may continue pembrolizumab for 12 more months alone or in conjunction with placebo vaccine if any is available. One week post RT, patients will receive weekly x 4 a dose of placebo vaccine. Placebo vaccine will then be given 21 days after the day 5 dose of temozolomide. Placebo vaccine will be given for 6 cycles or until supply runs out. Participants who receive placebo will be matched for number of vaccine injections that were generated by their tumor tissue. At one year, if patients are doing well, they may continue pembrolizumab for 12 more months alone or in conjunction with placebo vaccine if any is available. Temozolomide: TMZ will be administered on day 1 of radiation therapy (before RT treatment) and continue throughout RT at the dose of 75 mg/m^2. Post RT: The starting TMZ dose will be 150 mg/m^2/day for cycle 1, days 1-5, with a single dose escalation to 200 mg/m^2/day (days 29-33) and for all subsequent treatment if no treatment-related adverse events greater than Grade 2 are noted. TMZ will be given for 6 cycles. |
| BG002 | Ancillary Treatment | Radiation therapy (RT) + Temozolomide (TMZ) + Pembrolizumab. Pembrolizumab at 200mg will be administered on day 1 as a 30-minute intravenous (IV) infusion (prior to radiation therapy during RT phase) every 3 weeks on days 1, 22 and 43. Post RT, participants continue on Pembrolizumab 200mg on day 1 as 30-minute IV infusion every 3 weeks on days 1, 22, and 43. After completion of 6 cycles, participants may continue on Pembrolizumab for an additional 12 months if felt to be of benefit by the treating physician. Temozolomide: TMZ will be administered on day 1 of radiation therapy (before RT treatment) and continue throughout RT at the dose of 75 mg/m^2. Post RT: The starting TMZ dose will be 150 mg/m^2/day for cycle 1, days 1-5, with a single dose escalation to 200 mg/m^2/day (days 29-33) and for all subsequent treatment if no treatment-related adverse events greater than Grade 2 are noted. TMZ will be given for 6 cycles. |
| BG003 | Enrolled But Not Treated | Participants were enrolled but not treated. |
| BG004 | Total | Total of all reporting groups |
| Participants |
|
| Age, Continuous | Mean | Standard Deviation | years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| OG001 | Placebo | Radiation therapy (RT)+Temozolomide (TZ)+Pembrolizumab+Placebo Vaccine. Pembrolizumab at 200mg will be administered on day 1 as a 30-minute intravenous (IV) infusion (prior to radiation therapy during RT phase) every 3 weeks on days 1, 22 and 43. Post RT, participants continue on Pembrolizumab 200mg on day 1 as a 30-minute IV infusion every 3 weeks on days 1, 22, and 43. At one year, if participants are doing well, they may continue pembrolizumab for 12 more months alone or in conjunction with placebo vaccine if any is available. One week post RT, patients will receive weekly x 4 a dose of placebo vaccine. Placebo vaccine will then be given 21 days after the day 5 dose of temozolomide. Placebo vaccine will be given for 6 cycles or until supply runs out. Participants who receive placebo will be matched for number of vaccine injections that were generated by their tumor tissue. At one year, if patients are doing well, they may continue pembrolizumab for 12 more months alone or in conjunction with placebo vaccine if any is available. Temozolomide: TMZ will be administered on day 1 of radiation therapy (before RT treatment) and continue throughout RT at the dose of 75 mg/m^2. Post RT: The starting TMZ dose will be 150 mg/m^2/day for cycle 1, days 1-5, with a single dose escalation to 200 mg/m^2/day (days 29-33) and for all subsequent treatment if no treatment-related adverse events greater than Grade 2 are noted. TMZ will be given for 6 cycles. |
| OG002 | Ancillary Treatment | Radiation therapy (RT) + Temozolomide (TMZ) + Pembrolizumab. Pembrolizumab at 200mg will be administered on day 1 as a 30-minute intravenous (IV) infusion (prior to radiation therapy during RT phase) every 3 weeks on days 1, 22 and 43. Post RT, participants continue on Pembrolizumab 200mg on day 1 as 30-minute IV infusion every 3 weeks on days 1, 22, and 43. After completion of 6 cycles, participants may continue on Pembrolizumab for an additional 12 months if felt to be of benefit by the treating physician. Temozolomide: TMZ will be administered on day 1 of radiation therapy (before RT treatment) and continue throughout RT at the dose of 75 mg/m^2. Post RT: The starting TMZ dose will be 150 mg/m^2/day for cycle 1, days 1-5, with a single dose escalation to 200 mg/m^2/day (days 29-33) and for all subsequent treatment if no treatment-related adverse events greater than Grade 2 are noted. TMZ will be given for 6 cycles. |
|
|
| Secondary | Response Rate | Response was determined by the Response Assessment in Neuro-Oncology Criteria (RANO) criteria and reported with 95% confidence intervals using exact binomial probability distributions. Complete response is no T1 gadolinium enhancing disease or stable or decreasing T2/fluid-attenuated inversion recovery (FLAIR). Partial response is ≥ 50% decrease in T1 gadolinium enhancing disease or stable or decreasing T2/FLAIR. Stable disease is <50% decrease but <25% increase in T1 gadolinium enhancing disease or stable or decreasing T2/FLAIR. Progressive disease is ≥25% incT1 gadolinium enhancing disease, appearance of new lesions or increase in T2/FLAIR. | 4 out of 8 participants in vaccine group were evaluable for response. 6 out of the 9 participants in the placebo group were evaluable for response. 7 out of the 15 ancillary participants were evaluable for response. | Posted | Number | 95% Confidence Interval | percentage of participants | After treatment, up to 26 months |
|
|
|
| Secondary | Overall Survival (OS) | OS is defined as the time from registration to the time of death. Kaplan-Meier curves will be used to analyze overall survival. | Posted | Median | 95% Confidence Interval | Months | Time from registration to the time of death or off study up to 26 months |
|
|
|
| Secondary | Overall Survival at 6, 12 and 24 Months, Post-registration | Participants who are alive at 6, 12 and 24 months, post-registration determined from the level of the Kaplan-Meier curves at these time points. | Posted | Number | 95% Confidence Interval | Percentage of participants | 6, 12 and 24 months, post-registration |
|
|
|
| Secondary | Vaccine Cohort: Number of Adverse Events Grades 2-5, Unrelated, Unlikely, Possibly, Probably, and/or Definitely Related to Pembrolizumab | Adverse events were assessed by the Common Terminology Criteria for Adverse Events (CTCAE v5.0). Grade 2 is moderate. Grade 3 is severe. Grade 4 is life-threatening. And Grade 5 is death related to adverse event. | Posted | Number | adverse events | Start of treatment until participant is off study, approximately 61.5 months |
|
|
|
| Secondary | Placebo Cohort: Number of Adverse Events Grades 2-5, Unrelated, Unlikely, Possibly, Probably, and/or Definitely Related to Pembrolizumab | Adverse events were assessed by the Common Terminology Criteria for Adverse Events (CTCAE v5.0). Grade 2 is moderate. Grade 3 is severe. Grade 4 is life-threatening. And Grade 5 is death related to adverse event. | Posted | Number | Adverse events | Start of treatment until participant is off study, approximately 61.5 months |
|
|
|
| Secondary | Ancillary Treatment Cohort: Number of Adverse Events Grades 2-5, Unrelated, Unlikely, Possibly, Probably, and/or Definitely Related to Pembrolizumab | Adverse events were assessed by the Common Terminology Criteria for Adverse Events (CTCAE v5.0). Grade 2 is moderate. Grade 3 is severe. Grade 4 is life-threatening. And Grade 5 is death related to adverse event. | Posted | Number | Adverse Events | Start of treatment until participant is off study, approximately 61.5 months |
|
|
|
| Secondary | Mean Symptom Severity Using the MD Anderson Symptom Inventory-Brain Tumor Module (MDASI-BT). | To evaluate the occurrence of symptoms and correlate to disease progression and tolerance to treatment using the MD Anderson Symptom Inventory-Brain Tumor Module (MDASI-BT). Participants rate their symptoms on a questionnaire using an 11-point scale (0-10). 0 is "not present" and 10 is "as bad as you can imagine." Differences of at least 2 points will be classified as the minimum clinically meaningful change in the symptom severity measures. Higher score indicates worse severity. | There are different numbers for overall participants analyzed because we don't have that data available (i.e., a few participants didn't do a baseline questionnaire). | Posted | Mean | Standard Deviation | Score on a scale | Baseline, end of treatment or discontinuation, and 30 days after last dose |
|
|
|
| Secondary | Mean Symptom Interference Using the MD Anderson Symptom Inventory-Brain Tumor Module (MDASI-BT). | To evaluate the occurrence of symptoms and correlate to disease progression and tolerance to treatment using the MD Anderson Symptom Inventory-Brain Tumor Module (MDASI-BT). Participants rate their symptoms on a questionnaire using an 11-point scale (0-10) of how much symptoms interfered with different aspects of a patient's life in the last 24 hours such as general activity, mood, work, relations with other people, walking and enjoyment of life. 0 is "not present" and 10 is "as bad as you can imagine." Differences of at least 2 points will be classified as the minimum clinically meaningful change in the symptom severity measures. | There are different numbers for overall participants analyzed because we don't have that data available (i.e., a few participants didn't do a baseline questionnaire). | Posted | Mean | Standard Deviation | Score on a scale | Baseline, end of treatment or discontinuation, and 30 days after last dose |
|
|
|
| Secondary | Percentage of Participants Rating Their Symptom Severity to Be 5 or Greater (on a 0-10) Scale Using the MD Anderson Symptom Inventory-Brain Tumor Module (MDASI-BT) | Percentage of participants rating their symptom severity to be 5 or greater (on a 0-10) scale using the MD Anderson Symptom Inventory-Brain Tumor Module (MDASI-BT). Participants rate their symptoms on a questionnaire using an 11-point scale (0-10). 0 is "not present" and 10 is "as bad as you can imagine." | There are different numbers for overall participants analyzed because we don't have that data available (i.e., a few participants didn't do a baseline questionnaire). | Posted | Number | 95% Confidence Interval | Percentage of participants | Baseline, end of treatment or discontinuation, and 30 days after last dose |
|
|
|
| Secondary | Progression Free Survival (PFS) | PFS is defined as the time from registration to the time of confirmed progression. Progression was measured by the immunotherapy response assessment for neuro-oncology (iRANO) criteria. Progressive disease is ≥25% increase in the sum of bi-perpendicular diameters of enhancing disease or new lesions or significant worsened T2/fluid-attenuated inversion recovery (FLAIR) or significant clinical decline. | Posted | Median | 95% Confidence Interval | Months | Time from registration to the time of confirmed progression, an average of 9 months |
|
|
|
| Other Pre-specified | Number of Participants With Serious and/or Non-serious Adverse Events Assessed by the Common Terminology Criteria for Adverse Events (CTCAE v5.0) | Here is the number of participants with serious and/or non-serious adverse events assessed by the Common Terminology Criteria for Adverse Events (CTCAE v5.0). A non-serious adverse event is any untoward medical occurrence. A serious adverse event is an adverse event or suspected adverse reaction that results in death, a life-threatening adverse drug experience, hospitalization, disruption of the ability to conduct normal life functions, congenital anomaly/birth defect or important medical events that jeopardize the patient or subject and may require medical or surgical intervention to prevent one of the previous outcomes mentioned. | Posted | Count of Participants | Participants | Date treatment consent signed to date off study, approximately 61.5 months. |
|
|
|
| 6 |
| 8 |
| 6 |
| 8 |
| 8 |
| 8 |
| EG001 | Placebo | Radiation therapy (RT)+Temozolomide (TZ)+Pembrolizumab+Placebo Vaccine. Pembrolizumab at 200mg will be administered on day 1 as a 30-minute intravenous (IV) infusion (prior to radiation therapy during RT phase) every 3 weeks on days 1, 22 and 43. Post RT, participants continue on Pembrolizumab 200mg on day 1 as a 30-minute IV infusion every 3 weeks on days 1, 22, and 43. At one year, if participants are doing well, they may continue pembrolizumab for 12 more months alone or in conjunction with placebo vaccine if any is available. One week post RT, patients will receive weekly x 4 a dose of placebo vaccine. Placebo vaccine will then be given 21 days after the day 5 dose of temozolomide. Placebo vaccine will be given for 6 cycles or until supply runs out. Participants who receive placebo will be matched for number of vaccine injections that were generated by their tumor tissue. At one year, if patients are doing well, they may continue pembrolizumab for 12 more months alone or in conjunction with placebo vaccine if any is available. Temozolomide: TMZ will be administered on day 1 of radiation therapy (before RT treatment) and continue throughout RT at the dose of 75 mg/m^2. Post RT: The starting TMZ dose will be 150 mg/m^2/day for cycle 1, days 1-5, with a single dose escalation to 200 mg/m^2/day (days 29-33) and for all subsequent treatment if no treatment-related adverse events greater than Grade 2 are noted. TMZ will be given for 6 cycles. | 4 | 9 | 4 | 9 | 9 | 9 |
| EG002 | Ancillary Treatment | Radiation therapy (RT) + Temozolomide (TMZ) + Pembrolizumab. Pembrolizumab at 200mg will be administered on day 1 as a 30-minute intravenous (IV) infusion (prior to radiation therapy during RT phase) every 3 weeks on days 1, 22 and 43. Post RT, participants continue on Pembrolizumab 200mg on day 1 as 30-minute IV infusion every 3 weeks on days 1, 22, and 43. After completion of 6 cycles, participants may continue on Pembrolizumab for an additional 12 months if felt to be of benefit by the treating physician. Temozolomide: TMZ will be administered on day 1 of radiation therapy (before RT treatment) and continue throughout RT at the dose of 75 mg/m^2. Post RT: The starting TMZ dose will be 150 mg/m^2/day for cycle 1, days 1-5, with a single dose escalation to 200 mg/m^2/day (days 29-33) and for all subsequent treatment if no treatment-related adverse events greater than Grade 2 are noted. TMZ will be given for 6 cycles. | 10 | 15 | 8 | 15 | 12 | 15 |
| EG003 | Enrolled But Not Treated | Participants were enrolled but not treated. | 0 | 58 | 2 | 58 | 2 | 58 |
| Aspiration | Injury, poisoning and procedural complications | CTCAE (5.0) | Systematic Assessment |
|
| Blood and lymphatic system disorders - Other, hyponatremia | Blood and lymphatic system disorders | CTCAE (5.0) | Systematic Assessment |
|
| Confusion | Psychiatric disorders | CTCAE (5.0) | Systematic Assessment |
|
| Creatinine increased | Investigations | CTCAE (5.0) | Systematic Assessment |
|
| Dehydration | Metabolism and nutrition disorders | CTCAE (5.0) | Systematic Assessment |
|
| Diarrhea | Gastrointestinal disorders | CTCAE (5.0) | Systematic Assessment |
|
| Disease progression | General disorders | CTCAE (5.0) | Systematic Assessment |
|
| Edema cerebral | Nervous system disorders | CTCAE (5.0) | Systematic Assessment |
|
| Encephalopathy | Nervous system disorders | CTCAE (5.0) | Systematic Assessment |
|
| Fatigue | General disorders | CTCAE (5.0) | Systematic Assessment |
|
| Febrile neutropenia | Blood and lymphatic system disorders | CTCAE (5.0) | Systematic Assessment |
|
| Fever | General disorders | CTCAE (5.0) | Systematic Assessment |
|
| Generalized muscle weakness | Musculoskeletal and connective tissue disorders | CTCAE (5.0) | Systematic Assessment |
|
| Headache | Nervous system disorders | CTCAE (5.0) | Systematic Assessment |
|
| Hydrocephalus | Nervous system disorders | CTCAE (5.0) | Systematic Assessment |
|
| Hyperglycemia | Metabolism and nutrition disorders | CTCAE (5.0) | Systematic Assessment |
|
| Hypertension | Vascular disorders | CTCAE (5.0) | Systematic Assessment |
|
| Hyponatremia | Metabolism and nutrition disorders | CTCAE (5.0) | Systematic Assessment |
|
| Hypotension | Vascular disorders | CTCAE (5.0) | Systematic Assessment |
|
| Intracranial hemorrhage | Nervous system disorders | CTCAE (5.0) | Systematic Assessment |
|
| Muscle weakness left-sided | Musculoskeletal and connective tissue disorders | CTCAE (5.0) | Systematic Assessment |
|
| Muscle weakness right-sided | Musculoskeletal and connective tissue disorders | CTCAE (5.0) | Systematic Assessment |
|
| Nausea | Gastrointestinal disorders | CTCAE (5.0) | Systematic Assessment |
|
| Nervous system disorders - Other, altered mental status | Nervous system disorders | CTCAE (5.0) | Systematic Assessment |
|
| Seizure | Nervous system disorders | CTCAE (5.0) | Systematic Assessment |
|
| Sepsis | Infections and infestations | CTCAE (5.0) | Systematic Assessment |
|
| Sinus tachycardia | Cardiac disorders | CTCAE (5.0) | Systematic Assessment |
|
| Somnolence | Nervous system disorders | CTCAE (5.0) | Systematic Assessment |
|
| Supraventricular tachycardia | Cardiac disorders | CTCAE (5.0) | Systematic Assessment |
|
| Thromboembolic event | Vascular disorders | CTCAE (5.0) | Systematic Assessment |
|
| Urinary incontinence | Renal and urinary disorders | CTCAE (5.0) | Systematic Assessment |
|
| Urinary tract infection | Infections and infestations | CTCAE (5.0) | Systematic Assessment |
|
| Vomiting | Gastrointestinal disorders | CTCAE (5.0) | Systematic Assessment |
|
| Stroke | Nervous system disorders | CTCAE (5.0) | Systematic Assessment |
|
| Acidosis | Metabolism and nutrition disorders | CTCAE (5.0) | Systematic Assessment |
|
| Activated partial thromboplastin time prolonged | Investigations | CTCAE (5.0) | Systematic Assessment |
|
| Adrenal insufficiency | Endocrine disorders | CTCAE (5.0) | Systematic Assessment |
|
| Agitation | Psychiatric disorders | CTCAE (5.0) | Systematic Assessment |
|
| Alanine aminotransferase increased | Investigations | CTCAE (5.0) | Systematic Assessment |
|
| Alkaline phosphatase increased | Investigations | CTCAE (5.0) | Systematic Assessment |
|
| Alkalosis | Metabolism and nutrition disorders | CTCAE (5.0) | Systematic Assessment |
|
| Alopecia | Skin and subcutaneous tissue disorders | CTCAE (5.0) | Systematic Assessment |
|
| Anemia | Blood and lymphatic system disorders | CTCAE (5.0) | Systematic Assessment |
|
| Anorexia | Metabolism and nutrition disorders | CTCAE (5.0) | Systematic Assessment |
|
| Anxiety | Psychiatric disorders | CTCAE (5.0) | Systematic Assessment |
|
| Arthralgia | Musculoskeletal and connective tissue disorders | CTCAE (5.0) | Systematic Assessment |
|
| Aspartate aminotransferase increased | Investigations | CTCAE (5.0) | Systematic Assessment |
|
| Back pain | Musculoskeletal and connective tissue disorders | CTCAE (5.0) | Systematic Assessment |
|
| Blood bicarbonate decreased | Investigations | CTCAE (5.0) | Systematic Assessment |
|
| Blood bilirubin increased | Investigations | CTCAE (5.0) | Systematic Assessment |
|
| Blurred vision | Eye disorders | CTCAE (5.0) | Systematic Assessment |
|
| Breast pain | Reproductive system and breast disorders | CTCAE (5.0) | Systematic Assessment |
|
| Chills | General disorders | CTCAE (5.0) | Systematic Assessment |
|
| Cognitive disturbance | Nervous system disorders | CTCAE (5.0) | Systematic Assessment |
|
| Confusion | Psychiatric disorders | CTCAE (5.0) | Systematic Assessment |
|
| Constipation | Gastrointestinal disorders | CTCAE (5.0) | Systematic Assessment |
|
| Cough | Respiratory, thoracic and mediastinal disorders | CTCAE (5.0) | Systematic Assessment |
|
| Creatinine increased | Investigations | CTCAE (5.0) | Systematic Assessment |
|
| Cytomegalovirus infection reactivation | Infections and infestations | CTCAE (5.0) | Systematic Assessment |
|
| Dehydration | Metabolism and nutrition disorders | CTCAE (5.0) | Systematic Assessment |
|
| Depression | Psychiatric disorders | CTCAE (5.0) | Systematic Assessment |
|
| Dermatitis | Skin and subcutaneous tissue disorders | CTCAE (5.0) | Systematic Assessment |
|
| Dermatitis radiation | Injury, poisoning and procedural complications | CTCAE (5.0) | Systematic Assessment |
|
| Diarrhea | Gastrointestinal disorders | CTCAE (5.0) | Systematic Assessment |
|
| Dizziness | Nervous system disorders | CTCAE (5.0) | Systematic Assessment |
|
| Dry eye | Eye disorders | CTCAE (5.0) | Systematic Assessment |
|
| Dry mouth | Gastrointestinal disorders | CTCAE (5.0) | Systematic Assessment |
|
| Dysarthria | Nervous system disorders | CTCAE (5.0) | Systematic Assessment |
|
| Dysgeusia | Nervous system disorders | CTCAE (5.0) | Systematic Assessment |
|
| Dyspepsia | Gastrointestinal disorders | CTCAE (5.0) | Systematic Assessment |
|
| Dysphagia | Gastrointestinal disorders | CTCAE (5.0) | Systematic Assessment |
|
| Dysphasia | Nervous system disorders | CTCAE (5.0) | Systematic Assessment |
|
| Dyspnea | Respiratory, thoracic and mediastinal disorders | CTCAE (5.0) | Systematic Assessment |
|
| Ear and labyrinth disorders - Other, Hearing Loss | Ear and labyrinth disorders | CTCAE (5.0) | Systematic Assessment |
|
| Ear pain | Ear and labyrinth disorders | CTCAE (5.0) | Systematic Assessment |
|
| Eczema | Skin and subcutaneous tissue disorders | CTCAE (5.0) | Systematic Assessment |
|
| Edema face | General disorders | CTCAE (5.0) | Systematic Assessment |
|
| Edema limbs | General disorders | CTCAE (5.0) | Systematic Assessment |
|
| Endocrine disorders - Other, Thyroiditis | Endocrine disorders | CTCAE (5.0) | Systematic Assessment |
|
| Erythema multiforme | Skin and subcutaneous tissue disorders | CTCAE (5.0) | Systematic Assessment |
|
| Eye disorders - Other, Eye Pressure | Eye disorders | CTCAE (5.0) | Systematic Assessment |
|
| Eye disorders - Other, left eye rotating lateral side | Eye disorders | CTCAE (5.0) | Systematic Assessment |
|
| Eye disorders - Other, left eyelid droop | Eye disorders | CTCAE (5.0) | Systematic Assessment |
|
| Facial muscle weakness | Musculoskeletal and connective tissue disorders | CTCAE (5.0) | Systematic Assessment |
|
| Fall | Injury, poisoning and procedural complications | CTCAE (5.0) | Systematic Assessment |
|
| Fatigue | General disorders | CTCAE (5.0) | Systematic Assessment |
|
| Fecal incontinence | Gastrointestinal disorders | CTCAE (5.0) | Systematic Assessment |
|
| Fever | General disorders | CTCAE (5.0) | Systematic Assessment |
|
| Floaters | Eye disorders | CTCAE (5.0) | Systematic Assessment |
|
| Gait disturbance | General disorders | CTCAE (5.0) | Systematic Assessment |
|
| Gastroesophageal reflux disease | Gastrointestinal disorders | CTCAE (5.0) | Systematic Assessment |
|
| Generalized muscle weakness | Musculoskeletal and connective tissue disorders | CTCAE (5.0) | Systematic Assessment |
|
| Headache | Nervous system disorders | CTCAE (5.0) | Systematic Assessment |
|
| Hearing impaired | Ear and labyrinth disorders | CTCAE (5.0) | Systematic Assessment |
|
| Hematoma | Vascular disorders | CTCAE (5.0) | Systematic Assessment |
|
| Hematuria | Renal and urinary disorders | CTCAE (5.0) | Systematic Assessment |
|
| Hyperglycemia | Metabolism and nutrition disorders | CTCAE (5.0) | Systematic Assessment |
|
| Hyperkalemia | Metabolism and nutrition disorders | CTCAE (5.0) | Systematic Assessment |
|
| Hypernatremia | Metabolism and nutrition disorders | CTCAE (5.0) | Systematic Assessment |
|
| Hyperphosphatemia | Metabolism and nutrition disorders | CTCAE (5.0) | Systematic Assessment |
|
| Hypertension | Vascular disorders | CTCAE (5.0) | Systematic Assessment |
|
| Hyperthyroidism | Endocrine disorders | CTCAE (5.0) | Systematic Assessment |
|
| Hypoalbuminemia | Metabolism and nutrition disorders | CTCAE (5.0) | Systematic Assessment |
|
| Hypocalcemia | Metabolism and nutrition disorders | CTCAE (5.0) | Systematic Assessment |
|
| Hypoglycemia | Metabolism and nutrition disorders | CTCAE (5.0) | Systematic Assessment |
|
| Hypokalemia | Metabolism and nutrition disorders | CTCAE (5.0) | Systematic Assessment |
|
| Hypomagnesemia | Metabolism and nutrition disorders | CTCAE (5.0) | Systematic Assessment |
|
| Hyponatremia | Metabolism and nutrition disorders | CTCAE (5.0) | Systematic Assessment |
|
| Hypophosphatemia | Metabolism and nutrition disorders | CTCAE (5.0) | Systematic Assessment |
|
| Hypotension | Vascular disorders | CTCAE (5.0) | Systematic Assessment |
|
| Hypothyroidism | Endocrine disorders | CTCAE (5.0) | Systematic Assessment |
|
| Infections and infestations - Other, COVID-19 | Infections and infestations | CTCAE (5.0) | Systematic Assessment |
|
| Insomnia | Psychiatric disorders | CTCAE (5.0) | Systematic Assessment |
|
| Left ear pain | Ear and labyrinth disorders | CTCAE (5.0) | Systematic Assessment |
|
| Lethargy | Nervous system disorders | CTCAE (5.0) | Systematic Assessment |
|
| Leukocytosis | Blood and lymphatic system disorders | CTCAE (5.0) | Systematic Assessment |
|
| Localized edema | General disorders | CTCAE (5.0) | Systematic Assessment |
|
| Lymphocyte count decreased | Investigations | CTCAE (5.0) | Systematic Assessment |
|
| Memory impairment | Nervous system disorders | CTCAE (5.0) | Systematic Assessment |
|
| Muscle cramp | Musculoskeletal and connective tissue disorders | CTCAE (5.0) | Systematic Assessment |
|
| Muscle weakness left-sided | Musculoskeletal and connective tissue disorders | CTCAE (5.0) | Systematic Assessment |
|
| Muscle weakness right-sided | Musculoskeletal and connective tissue disorders | CTCAE (5.0) | Systematic Assessment |
|
| Muscle weakness upper limb | Musculoskeletal and connective tissue disorders | CTCAE (5.0) | Systematic Assessment |
|
| Musculoskeletal and connective tissue disorder - Other, Bilateral Lower Extremity Pain | Musculoskeletal and connective tissue disorders | CTCAE (5.0) | Systematic Assessment |
|
| Musculoskeletal and connective tissue disorder - Other, Bilateral Shin Discomfort | Musculoskeletal and connective tissue disorders | CTCAE (5.0) | Systematic Assessment |
|
| Myalgia | Musculoskeletal and connective tissue disorders | CTCAE (5.0) | Systematic Assessment |
|
| Nausea | Gastrointestinal disorders | CTCAE (5.0) | Systematic Assessment |
|
| Neck pain | Musculoskeletal and connective tissue disorders | CTCAE (5.0) | Systematic Assessment |
|
| Nervous system disorders - Other, Phantosmia | Nervous system disorders | CTCAE (5.0) | Systematic Assessment |
|
| Nervous system disorders - Other, left hand numbness | Nervous system disorders | CTCAE (5.0) | Systematic Assessment |
|
| Nervous system disorders - Other, left hemineglect | Nervous system disorders | CTCAE (5.0) | Systematic Assessment |
|
| Neutrophil count decreased | Investigations | CTCAE (5.0) | Systematic Assessment |
|
| Oral hemorrhage | Gastrointestinal disorders | CTCAE (5.0) | Systematic Assessment |
|
| Pain | General disorders | CTCAE (5.0) | Systematic Assessment |
|
| Pain in extremity | Musculoskeletal and connective tissue disorders | CTCAE (5.0) | Systematic Assessment |
|
| Paresthesia | Nervous system disorders | CTCAE (5.0) | Systematic Assessment |
|
| Platelet count decreased | Investigations | CTCAE (5.0) | Systematic Assessment |
|
| Pruritus | Skin and subcutaneous tissue disorders | CTCAE (5.0) | Systematic Assessment |
|
| Pulmonary infiltrate | Respiratory, thoracic and mediastinal disorders | CTCAE (5.0) | Systematic Assessment |
|
| Rash acneiform | Skin and subcutaneous tissue disorders | CTCAE (5.0) | Systematic Assessment |
|
| Rash maculo-papular | Skin and subcutaneous tissue disorders | CTCAE (5.0) | Systematic Assessment |
|
| Renal and urinary disorders - Other, kidney stones | Renal and urinary disorders | CTCAE (5.0) | Systematic Assessment |
|
| Renal and urinary disorders - Other, polydypsia | Renal and urinary disorders | CTCAE (5.0) | Systematic Assessment |
|
| Renal and urinary disorders - Other, polyuria | Renal and urinary disorders | CTCAE (5.0) | Systematic Assessment |
|
| Renal colic | Renal and urinary disorders | CTCAE (5.0) | Systematic Assessment |
|
| Rhinorrhea | Respiratory, thoracic and mediastinal disorders | CTCAE (5.0) | Systematic Assessment |
|
| Scrotal infection | Infections and infestations | CTCAE (5.0) | Systematic Assessment |
|
| Seizure | Nervous system disorders | CTCAE (5.0) | Systematic Assessment |
|
| Sepsis | Infections and infestations | CTCAE (5.0) | Systematic Assessment |
|
| Sinus bradycardia | Cardiac disorders | CTCAE (5.0) | Systematic Assessment |
|
| Sinusitis | Infections and infestations | CTCAE (5.0) | Systematic Assessment |
|
| Skin and subcutaneous tissue disorders - Other, Increased Facial Hair | Skin and subcutaneous tissue disorders | CTCAE (5.0) | Systematic Assessment |
|
| Skin and subcutaneous tissue disorders - Other, Oral Lesion | Skin and subcutaneous tissue disorders | CTCAE (5.0) | Systematic Assessment |
|
| Skin and subcutaneous tissue disorders - Other, psoriasis(flare) | Skin and subcutaneous tissue disorders | CTCAE (5.0) | Systematic Assessment |
|
| Skin hyperpigmentation | Skin and subcutaneous tissue disorders | CTCAE (5.0) | Systematic Assessment |
|
| Skin ulceration | Skin and subcutaneous tissue disorders | CTCAE (5.0) | Systematic Assessment |
|
| Somnolence | Nervous system disorders | CTCAE (5.0) | Systematic Assessment |
|
| Stomach pain | Gastrointestinal disorders | CTCAE (5.0) | Systematic Assessment |
|
| Surgical and medical procedures - Other, Head pain | Surgical and medical procedures | CTCAE (5.0) | Systematic Assessment |
|
| Thromboembolic event | Vascular disorders | CTCAE (5.0) | Systematic Assessment |
|
| Thyroid stimulating hormone increased | Investigations | CTCAE (5.0) | Systematic Assessment |
|
| Tremor | Nervous system disorders | CTCAE (5.0) | Systematic Assessment |
|
| Urinary incontinence | Renal and urinary disorders | CTCAE (5.0) | Systematic Assessment |
|
| Urinary tract infection | Infections and infestations | CTCAE (5.0) | Systematic Assessment |
|
| Urticaria | Skin and subcutaneous tissue disorders | CTCAE (5.0) | Systematic Assessment |
|
| Vaccination site lymphadenopathy | General disorders | CTCAE (5.0) | Systematic Assessment |
|
| Ventricular arrhythmia | Cardiac disorders | CTCAE (5.0) | Systematic Assessment |
|
| Vision decreased | Eye disorders | CTCAE (5.0) | Systematic Assessment |
|
| Vomiting | Gastrointestinal disorders | CTCAE (5.0) | Systematic Assessment |
|
| Weight gain | Investigations | CTCAE (5.0) | Systematic Assessment |
|
| Weight loss | Investigations | CTCAE (5.0) | Systematic Assessment |
|
| White blood cell decreased | Investigations | CTCAE (5.0) | Systematic Assessment |
|
| Wound infection | Infections and infestations | CTCAE (5.0) | Systematic Assessment |
|
Not provided
Not provided
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
| D009375 | Neoplasms, Glandular and Epithelial |
| D009380 | Neoplasms, Nerve Tissue |
| D001393 |
| Azoles |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
|
| Stable Disease |
|
| Progressive Disease |
|
|
| 24 months post registration |
|
| Grade 3 |
|
| Grade 4 |
|
| Grade 5 |
|
| Grade 3 |
|
| Grade 4 |
|
| Grade 5 |
|
| Grade 3 |
|
| Grade 4 |
|
| Grade 5 |
|
| End of treatment or discontinuation |
|
|
| 30 days after last dose |
|
|
| End of treatment or discontinuation |
|
|
| 30 days after last dose |
|
|
| End of treatment or discontinuation |
|
|
| 30 days after last dose |
|
|