GlioblastomaPhase 1NCT03426891
Pembrolizumab and Vorinostat Combined With Temozolomide for Newly Diagnosed Glioblastoma
A Phase 1 study testing Pembrolizumab, Vorinostat and Temozolomide in people with Glioblastoma and Brain Tumor, run by H. Lee Moffitt Cancer Center and Research Institute at 1 site in United States.
Trial summary
The purpose of this research study is to test the safety and tolerability of the combination treatment of the investigational drugs vorinostat and pembrolizumab, in combination with chemotherapy (temozolomide), and radiotherapy. The U.S. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Glioblastoma, Brain Tumor, GBM
- What is being tested?
- Pembrolizumab, Vorinostat and Temozolomide
- Type of treatment
- Pill or oral medicine, Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 21 participants
- Where
- 1 siteUnited States
- Study dates
- 16 Mar 2018to 28 Jun 2023
- 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
- Newly diagnosed glioblastoma or gliosarcoma
- Histologically confirmed diagnosis of World Health Organization Grade IV malignant glioma
- An interval of ≥ 21 days since surgical resection prior to treatment on the trial
- Karnofsky performance status of 70 or higher
- Adequate organ function laboratory values
- Resting baseline O2 saturation by pulse oximetry of ≥ 92% at rest
Show all 14Show fewer
- Willing and able to provide written informed consent/assent for the trial.
- Life expectancy ≥ 12 weeks
- Willingness to discontinue medications known to be associated with risk of Torsades de Pointes such as quinidine, procainamide, disopyramide, amiodarone, erythromycin, clarithromycin, chlorpromazine and haloperidol
- Single lesion < 4 cm in longest diameter (diameter of enhancing lesion)
- Patient shouldn't have received any anti-cancer therapy for glioblastoma in past
- Females of childbearing potential (FOCBP) should have a negative urine or serum pregnancy prior to receiving the first dose of study medication. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
- Females and males of childbearing potential must be willing to use an adequate method of contraception per protocol for the course of the study through 120 days after the last dose of study medication. Note: Abstinence is acceptable if this is the usual lifestyle and preferred contraception for participant.
- Use of Optune device is allowed.
Who cannot join
- Had prior treatment of glioblastoma (GBM) with radiation and temozolomide
- Has evidence of leptomeningeal disease
- Had prior treatment with Gliadel
- Unable (due to existent medical condition) or unwilling to have a contrast enhanced MRI of brain
- Currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks of the first dose of treatment
- Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment. Physiologic doses of steroid therapy (≤ 2 mg/day dexamethasone equivalents) by the time of first dose of treatment are allowed.
Show all 22Show fewer
- Has a known history of active Bacillus Tuberculosis (TB)
- Hypersensitivity to pembrolizumab or any of its excipients
- Has had a prior anti-cancer monoclonal antibody (mAb) within 4 weeks prior to study Day 1 or who has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to agents administered more than 4 weeks earlier
- Has had prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to study Day 1 or who has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to a previously administered agent. Note: Potential participants with ≤ Grade 2 neuropathy are an exception to this criterion and may qualify for the study. Note: If patient received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy.
- Has a known additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer.
- Has active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment. Patients with vitiligo or resolved childhood asthma/atopy would be an exception to this rule. Patients that require intermittent use of bronchodilators or local steroid injections would not be excluded from the study. Patients with hypothyroidism stable on hormone replacement or Sjorgen's syndrome will not be excluded from the study.
- Has known history of, or any evidence of active, interstitial lung disease or non-infectious pneumonitis requiring corticosteroid therapy
- Has an active serious infection requiring systemic therapy
- Had major surgical procedure, open biopsy, or significant traumatic injury within 21 days prior to day 1 of treatment on study
- Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the patient's participation for the full duration of the trial, or is not in the best interest of the patient to participate
- Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial
- 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.
- Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent.
- Has a known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies).
- Has known active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., HCV RNA [qualitative] is detected).
- Has received a live vaccine within 30 days of planned start of study therapy. Note: Seasonal influenza vaccines for injection are generally inactivated flu vaccines and are allowed; however intranasal influenza vaccines (e.g., Flu-Mist®) are live attenuated vaccines, and are not allowed.
Trial locations and contacts
1 site in 1 country.
United States1 site
H. Lee Moffitt Cancer Center and Research Institute
Tampa, Florida, 33612
About this study
Official title: A Phase I Trial of Pembrolizumab and Vorinostat Combined With Temozolomide and Radiation Therapy for Newly Diagnosed Glioblastoma
The purpose of this research study is to test the safety and tolerability of the combination treatment of the investigational drugs vorinostat and pembrolizumab, in combination with chemotherapy (temozolomide), and radiotherapy. The U.S. Food and Drug Administration (FDA) has approved pembrolizumab for use to treat a deadly skin cancer called melanoma and lung cancer and vorinostat to treat some forms of blood and lymph node cancers. However, both vorinostat and pembrolizumab are considered investigational drugs in this study because they are not approved for treatment of glioblastoma.
- Conditions
- Glioblastoma, Brain Tumor, GBM
- Being tested
- Pembrolizumab, Vorinostat, Temozolomide, Radiotherapy
- Keywords
- Immunotherapy, Radiotherapy, Glioblastoma
- Medical subject headings
- Glioblastoma, Brain Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PembrolizumabDrug
Also called Keytruda, immunotherapy
200 mg intravenously (IV) every 3 weeks. The dose of pembrolizumab will remain the same throughout study treatment. During the maintenance phase, participants will receive pembrolizumab (for 12 months).
VorinostatDrug
Also called Zolinza™, chemotherapy, histone deacetylase inhibitor
Dose Escalation Level -1 vorinostat 100 mg/day by mouth on days 1-5 every week during radiotherapy starting on first day of radiotherapy and 300 mg/day 1 week on 1 week off after radiotherapy. Level 1:vorinostat 200 mg/day by mouth on day 1-5 every week during radiotherapy, starting on first day of radiotherapy; and 300 mg/day 1 week on 1 week off after radiotherapy. Dose Escalation Level 2: vorinostat 300 mg/day by mouth on days 1-5 every week during radiotherapy, starting on first day of radiotherapy; and 400 mg/day 1 week on 1 week off after radiotherapy.
TemozolomideDrug
Also called chemotherapy, Temodar, TMZ
All participants will receive standard Temozolomide: Temozolomide (chemotherapy) 75 mg/m^2/day by mouth administered during the course of radiotherapy. Temozolomide will be administered continuously from Day 1 of radiotherapy to the last day of radiation. Maintenance Phase: temozolomide will start 4 weeks (+/- 3 days) after last dose of radiotherapy and will continue for 6 cycles post radiotherapy (150-200 mg/m^2/day, days 1-5 every 4 weeks) as per standard of care. During the maintenance phase, participants will receive Temozolomide (for the first 6 months).
RadiotherapyRadiation
Also called radiation therapy
All participants will receive standard radiotherapy: a total dose of 60 Gy administered in daily doses of 2 Gy, typically on a 5 days on / 2 days off schedule over 6 - 7 weeks.
| Study group | Role | What they receive |
|---|---|---|
| Dose Escalation Phase | Experimental | Level -1: Vorinostat 100 mg/day PO during RTX; 300 mg/day PO after RTX Level 1: Vorinostat 200 mg/day PO during RTX; 300 mg/day PO after RTX Receives: Drug: Pembrolizumab; Drug: Vorinostat; Drug: Temozolomide; Radiation: Radiotherapy |
| Radiotherapy and Maintenance Phase | Experimental | 100 mg/day Vorinostat (+200 mg Pembro) with radiotherapy and 400 mg/day Vorinostat (+200 mg Pembro) maintenance. Receives: Drug: Pembrolizumab; Drug: Vorinostat; Drug: Temozolomide; Radiation: Radiotherapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximum Tolerated Dose (MTD)
The maximum tolerated dose (MTD)/recommended dose expansion dose of vorinostat given in combination with pembrolizumab, temozolomide, and radiotherapy in patients with newly diagnosed glioblastoma. Toxicities will be graded in severity according to the NCI Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0 for toxicity categories as outlined in the study protocol.
Measured: 12 weeks
Secondary outcomes (1)
Overall Survival (OS)
Median overall survival rate, 95% confidence survival. OS: Time from randomization until death from any cause.
Measured: Up to 24 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Feb 2018
- Study start16 Mar 2018
- Primary completion18 Oct 2021
- Study completion28 Jun 2023
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.
- More trials run by H. Lee Moffitt Cancer Center and Research InstituteThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 21 participants (actual)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Collaborators
- Merck Sharp & Dohme LLC
- Responsible party
- Sponsor
- Investigators
- Peter Forsyth, M.D., Principal investigator, H. Lee Moffitt Cancer Center and Research Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03426891
- Sponsor's protocol ID
- MCC-19342
- Status last verified
- Sep 2025
- First submitted
- 2 Feb 2018
- Last updated
- 6 Oct 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 6 Oct 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I Trial of Pembrolizumab and Vorinostat Combined With Temozolomide and Radiation Therapy for Newly Diagnosed Glioblastoma
- ClinicalTrials.gov ID
- NCT03426891
- Acronym / sponsor ID
- MCC-19342
- Conditions
- Glioblastoma, Brain Tumor, GBM
- Keywords
- Immunotherapy, Radiotherapy, Glioblastoma
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 21 participants (actual)
- Lead sponsor
- H. Lee Moffitt Cancer Center and Research InstituteUniversity, hospital or other
- Collaborators
- Merck Sharp & Dohme LLC
- Study start
- 16 Mar 2018 (actual)
- Primary completion
- 18 Oct 2021 (actual)
- Study completion
- 28 Jun 2023 (actual)
- First posted
- 8 Feb 2018 (actual)
- Results
- Posted 6 Oct 2025
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this research study is to test the safety and tolerability of the combination treatment of the investigational drugs vorinostat and pembrolizumab, in combination with chemotherapy (temozolomide), and radiotherapy. The U.S. Food and Drug Administration (FDA) has approved pembrolizumab for use to treat a deadly skin cancer called melanoma and lung cancer and vorinostat to treat some forms of blood and lymph node cancers. However, both vorinostat and pembrolizumab are considered investigational drugs in this study because they are not approved for treatment of glioblastoma.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Dose Escalation Phase | Experimental | Drug: Pembrolizumab, Drug: Vorinostat, Drug: Temozolomide, Radiation: RadiotherapyLevel -1: Vorinostat 100 mg/day PO during RTX; 300 mg/day PO after RTX Level 1: Vorinostat 200 mg/day PO during RTX; 300 mg/day PO after RTX |
| Radiotherapy and Maintenance Phase | Experimental | Drug: Pembrolizumab, Drug: Vorinostat, Drug: Temozolomide, Radiation: Radiotherapy100 mg/day Vorinostat (+200 mg Pembro) with radiotherapy and 400 mg/day Vorinostat (+200 mg Pembro) maintenance. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (14 listed)
- Newly diagnosed glioblastoma or gliosarcoma
- Histologically confirmed diagnosis of World Health Organization Grade IV malignant glioma
- An interval of ≥ 21 days since surgical resection prior to treatment on the trial
- Karnofsky performance status of 70 or higher
- Adequate organ function laboratory values
Key exclusion criteria (22 listed)
- Had prior treatment of glioblastoma (GBM) with radiation and temozolomide
- Has evidence of leptomeningeal disease
- Had prior treatment with Gliadel
- Unable (due to existent medical condition) or unwilling to have a contrast enhanced MRI of brain
- Currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks of the first dose of treatment
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 |
|---|---|---|
| PembrolizumabAlso: Keytruda, immunotherapy200 mg intravenously (IV) every 3 weeks. The dose of pembrolizumab will remain the same throughout study treatment. During the maintenance phase, participants will receive pembrolizumab (for 12 months). | Drug | Dose Escalation Phase, Radiotherapy and Maintenance Phase |
| VorinostatAlso: Zolinza™, chemotherapy, histone deacetylase inhibitorDose Escalation Level -1 vorinostat 100 mg/day by mouth on days 1-5 every week during radiotherapy starting on first day of radiotherapy and 300 mg/day 1 week on 1 week off after radiotherapy. Level 1:vorinostat 200 mg/day by mouth on day 1-5 every week during radiotherapy, starting on first day of radiotherapy; and 300 mg/day 1 week on 1 week off after radiotherapy. Dose Escalation Level 2: vorinostat 300 mg/day by mouth on days 1-5 every week during radiotherapy, starting on first day of radiotherapy; and 400 mg/day 1 week on 1 week off after radiotherapy. | Drug | Dose Escalation Phase, Radiotherapy and Maintenance Phase |
| TemozolomideAlso: chemotherapy, Temodar, TMZAll participants will receive standard Temozolomide: Temozolomide (chemotherapy) 75 mg/m^2/day by mouth administered during the course of radiotherapy. Temozolomide will be administered continuously from Day 1 of radiotherapy to the last day of radiation. Maintenance Phase: temozolomide will start 4 weeks (+/- 3 days) after last dose of radiotherapy and will continue for 6 cycles post radiotherapy (150-200 mg/m^2/day, days 1-5 every 4 weeks) as per standard of care. During the maintenance phase, participants will receive Temozolomide (for the first 6 months). | Drug | Dose Escalation Phase, Radiotherapy and Maintenance Phase |
| RadiotherapyAlso: radiation therapyAll participants will receive standard radiotherapy: a total dose of 60 Gy administered in daily doses of 2 Gy, typically on a 5 days on / 2 days off schedule over 6 - 7 weeks. | Radiation | Dose Escalation Phase, Radiotherapy and Maintenance Phase |
Primary outcome
Maximum Tolerated Dose (MTD)
Time frame: 12 weeks
The maximum tolerated dose (MTD)/recommended dose expansion dose of vorinostat given in combination with pembrolizumab, temozolomide, and radiotherapy in patients with newly diagnosed glioblastoma. Toxicities will be graded in severity according to the NCI Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0 for toxicity categories as outlined in the study protocol.
1 secondary outcome
Overall Survival (OS)
Time frame: Up to 24 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Oct 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Moffitt Cancer Center Clinical Trials websiteLink provided by the sponsor.
Related trials for Glioblastoma
Active, not recruitingPhase 3
EF-41/KEYNOTE D58: Phase 3 Study of Optune Concomitant With Temozolomide Plus Pembrolizumab in Newly Diagnosed Glioblastoma
Glioblastoma
RecruitingPhase 3
Beginning Radiation Immediately With GammaTile at GBM Excision Versus Standard of Care
Glioblastoma
RecruitingPhase 1/2
Testing the Addition of an Anti-cancer Drug, Selinexor, to the Usual Chemotherapy Treatment (Temozolomide) for Brain Tumors That Have Returned After Previous Treatment
Recurrent Glioblastoma, IDH-Wildtype, Recurrent MGMT-Methylated Glioblastoma
Active, not recruitingPhase 1
Oral Gallium Maltolate for the Treatment of Relapsed and Refractory Glioblastoma
Glioblastoma
RecruitingPhase 1/2
PLX038 in Primary Central Nervous System Tumors Containing MYC or MYCN Amplifications
Glioma, Medulloblastoma
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.
Peter Forsyth, M.D. principal investigator
H. Lee Moffitt Cancer Center and Research Institute
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Pembrolizumab, Vorinostat and Temozolomide in people with Glioblastoma and Brain Tumor, run by H. Lee Moffitt Cancer Center and Research Institute 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 14 inclusion and 22 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: finished, as of the sponsor's last update on 6 Oct 2025. 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 6 Oct 2025). 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?
Maximum Tolerated Dose (MTD) (time frame: 12 weeks). 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 6 Oct 2025.