Malignant GliomaPhase 1/2NCT02311582
MK-3475 in Combination With MRI-guided Laser Ablation in Recurrent Malignant Gliomas
A Phase 1/2 study testing MK-3475 and MRI-guided laser ablation in people with Malignant Glioma, run by Washington University School of Medicine at 2 sites in United States.
Trial summary
The blood brain barrier (BBB) is a major obstacle to drug delivery in the treatment of malignant brain tumors including glioblastoma multiforme (GBM). MRI-guided laser ablation (MLA) has been noted to disrupt peritumoral the blood brain barrier (BBB), which may then lead to increased access of new tumor antigens to… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Malignant Glioma
- What is being tested?
- MK-3475 and MRI-guided laser ablation
- Type of treatment
- Injection or infusion, Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 55 participants
- Where
- 2 sitesUnited States
- Study dates
- 5 Aug 2015to 15 Apr 2024
- Phase
- Phase 1/2
- 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
- Phase I: Histologically confirmed grade III or IV malignant glioma.
- Phase II: Histologically confirmed grade IV malignant glioma (GBM).
- Note: GBM variants and suspected secondary GBM are allowed for both phase I and phase II.
- Unequivocal evidence of tumor progression as documented by biopsy or brain MRI scan per RANO criteria.
- There must be an interval of at least 12 weeks from the completion of standard front-line therapy to study registration unless there is unequivocal evidence for tumor recurrence per RANO criteria. When the interval is less than 12 weeks, the use of perfusion imaging and/or PET scan is allowed to differentiate between unequivocal evidence of tumor recurrence and pseudoprogression. Standard front-line therapy is as described below:
- For grade IV malignant gliomas (GBM): Standard front line therapy for newly diagnosed GBM must include maximal feasible surgical resection (biopsy alone allowed), radiotherapy, and temozolomide chemotherapy. If the tumor was initially diagnosed as either a grade II or III tumor and now has recurred or progressed as a grade IV GBM, it will be considered a secondary recurrent grade IV GBM and will be eligible for this study as long as prior treatment included maximal feasible surgical resection (biopsy alone allowed), radiotherapy, and temozolomide chemotherapy.
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- For grade III malignant gliomas with 1p 19q codeletions: Standard front line therapy for newly diagnosed grade III malignant gliomas must include maximal feasible surgical resection (biopsy alone allowed), radiotherapy, and chemotherapy (PCV or temozolomide). If the patient did not receive any or all components of the standard front line therapy as detailed above for newly diagnosed grade III gliomas and the tumor then recurred or progressed, s/he must first receive at least one prior standard therapy or any appropriate combination of the components of standard therapy as detailed above and must experience further recurrence or progression before s/he is deemed eligible for this study. If the tumor was initially diagnosed as a grade II glioma with 1p 19q codeletions and now has recurred or progressed as a grade III tumor, it will be considered a secondary recurrent grade III glioma with 1p 19q codeletions and will be eligible for this study as long as prior treatment included maximal feasible surgical resection (biopsy alone allowed), radiotherapy, and chemotherapy (PCV or temozolomide).
- For grade III malignant gliomas without 1p 19q codeletions: Standard front-line therapy for newly diagnosed grade III malignant gliomas must include maximal feasible surgical resection (biopsy alone allowed), radiotherapy, and temozolomide chemotherapy. If the tumor was initially diagnosed as a grade II glioma without 1p 19q codeletions and now has recurred or progressed as a grade III tumor, it will be considered a secondary recurrent grade III glioma without 1p 19q codeletions and will be eligible for this study as long as prior treatment included maximal feasible surgical resection (biopsy alone allowed), radiotherapy, and temozolomide chemotherapy.
- Candidate for MLA based on the size, location, and shape of the recurrent tumor as determined by the performing neurosurgeon. Surgical resection/debulking prior to MLA is allowed per standard of care but is not required; if the patient undergoes resection or debulking, it must have occurred at least 3 weeks prior to the first dose of MK-3475. For Phase II: if surgical resection/debulking prior to MLA is not indicated, a biopsy of the tumor will be done at the same time of MLA to obtain tumor tissue for both diagnostic purposes and immune monitoring.
- Patients who have undergone a resection for recurrence will be eligible. In those who have undergone a gross total resection, the MLA will be directed at treating a peritumoral margin of 0.5-1cm surrounding the resection cavity to disrupt the BBB and potentially increase access of MK-3475 to the peritumoral infiltrating glioma cells.
- At least 18 years of age.
- Karnofsky ≥ 60%
- Normal bone marrow and organ function as defined below:
- ANC ≥ 1,500/mcL
- Platelets ≥ 100,000/mcL
- Hemoglobin ≥ 9 g/dL or ≥ 5.6 mmol/L
- Serum creatinine ≤ 1.5 x IULN OR creatinine clearance by Cockcroft-Gault ≥ 60 mL/min for patients with serum creatinine > 1.5 x IULN
- Serum total bilirubin ≤ 1.5 x IULN OR direct bilirubin ≤ IULN for patients with total bilirubin > 1.5 x IULN
- AST (SGOT) and ALT (SGPT) ≤ 2.5 x IULN (or ≤ 5 x IULN for patients with liver metastases)
- INR or PT ≤ 1.5 x IULN unless patient is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants
- aPTT ≤ 1.5 x IULN unless patient is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants
- Sexually active women of childbearing potential and men must agree to use contraception (as described in the protocol) prior to study entry, for the duration of study participation, and for 120 days after last dose of MK-3475. Should a woman become pregnant or suspect she is pregnant while participating in this study, she must inform her treating physician immediately.
- Patients with the ability to understand and willingness to sign an IRB approved written informed consent document will be enrolled into the trial. However, should a patient lose their ability to consent while participating in this study and s/he is still receiving clinical benefit from participation, s/he may continue on study with the consent of a Legally Authorized Representative.
Who cannot join
- Prior treatment with any anti-angiogenic agent (including bevacizumab).
- Prior treatment with an anti-PD-1, anti-PD-L1, anti-PD-L2, or 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).
- Prior treatment with a monoclonal antibody within 4 weeks prior to the first dose of MK-3475 or has not recovered (i.e. ≤ grade 1 or at baseline) from adverse events due to agents administered more than 4 weeks earlier.
- Prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to the first dose of MK-3475 or has not recovered (i.e. ≤ grade 1 or at baseline) from adverse events due to a previously administered agent.
- Note: patients with ≤ grade 2 neuropathy are an exception to this criterion and may qualify for the study.
- Note: if a patient underwent major surgery, s/he must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy.
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- Candidates for curative resection or urgent surgical procedure(s) needed.
- Presence of infratentorial lesions, brainstem lesions, or lesions that are less than 5 mm from the hyophysis or cranial nerves.
- Multifocal gliomas that are bilateral. Patients with unilateral multifocal gliomas may be eligible if their multifocal disease can be treated effectively and safely in a single MLA procedure.
- Presence of leptomeningeal metastases.
- Recent (within 8 weeks) history of CNS hemorrhage unless the hemorrhage is located within the tumor that will be removed en total during surgical debulking or ablated during MLA.
- Requires therapeutic doses of anticoagulants unless anticoagulation can be safely discontinued before surgery per standard practice (e.g. first DVD for which anticoagulation has been at least 3 months and repeat imaging demonstrates resolution of DVT) or an IVC filter can be used in place of anticoagulation. Subjects are permitted to resume anticoagulation following surgery per discretion of treating physician and/or site SOPs
- Received prior local therapy (stereotactic radiosurgery, brachytherapy, or carmustine wafers) to the proposed area of MLA treatment.
- Received a live vaccine or live-attenuated vaccine within 30 days prior to the first dose of MK-3475. Administration of killed vaccines is allowed.
- Currently receiving any other investigational agents or has participated in a study of an investigational agent or using an investigational device within 3 weeks of the first dose of MK-3475.
- A history of allergic reactions attributed to compounds of similar chemical or biologic composition to MK-3475 or other agents used in the study.
- Dexamethasone > 4 mg daily at the time of registration
- Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment (with the exception of daily dexamethasone ≤ 4 mg).
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, uncontrolled hypertension, or psychiatric illness/social situations that would limit compliance with study requirements.
- Has an active autoimmune disease requiring systemic treatment within 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.
- Has a history of (non-infectious) pneumonitis/interstitial lung disease that required steroids or current pneumonitis/interstitial lung disease.
- Pregnant and/or breastfeeding. Patient must have a negative serum or urine pregnancy test within 72 hours of study entry.
- Known history of hepatitis B (e.g.,defined as hepatitis B surface antigen [HBsAg] reactive) or known active hepatitis C virus (e.g.,defined as HCV RNA [qualitative] is detected) infection.
- Known history of active TB (bacillus tuberculosis).
- Known history of HIV (HIV 1/2 antibodies).
Trial locations and contacts
2 sites in 1 country.
United States2 sites
University of Florida
Gainesville, Florida, 32611
Washington University School of Medicine
St Louis, Missouri, 63110
About this study
Official title: A Phase I/II Study Testing the Safety, Toxicities, and Efficacy of MK-3475 in Combination With MRI-guided Laser Ablation in Recurrent Malignant Gliomas
The blood brain barrier (BBB) is a major obstacle to drug delivery in the treatment of malignant brain tumors including glioblastoma multiforme (GBM). MRI-guided laser ablation (MLA) has been noted to disrupt peritumoral the blood brain barrier (BBB), which may then lead to increased access of new tumor antigens to the lymphovascular system and vice versa of immune effector cells to the tumor for effective activation of the immune system, and tumor infiltration, respectively. Therefore, the combination of MK-3475 and MLA as proposed in this protocol is hypothesized to create a therapeutic combinatorial effect in which MLA increases material access to promote immune activation and then MK-3475 maximizes these tumor-specific immune reactions to impart effective tumor control.
- Conditions
- Malignant Glioma
- Being tested
- MK-3475, MRI-guided laser ablation
- Medical subject headings
- Glioma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MK-3475Biological
Also called Pembrolizumab, Keytruda
Patients currently on pembrolizumab beyond the 2 year/35 cycle limit at the time of the approval of Amendment 13 (approved 07/28/2021) may continue to receive pembrolizumab unless there is progression, toxicity or agreement by the patient and PI to come off therapy. Participants who discontinue pembrolizumab after receiving 35 doses are eligible for retreatment with pembrolizumab if they progress during follow-up provided they meet the requirements. Participants may receive an additional 17 cycles (12 months) of pembrolizumab during the Second Course Phase (Retreatment).
MRI-guided laser ablationDevice
Also called MLA, NeuroBlate, AutoLITT
MLA is a minimally invasive laser surgery, which employs a small incision in the scalp and skull, through which a thin laser probe is inserted and guided by MR imaging to the core of the tumor mass where it delivers hyperthermic ablation from the core to the rim.
| Study group | Role | What they receive |
|---|---|---|
| Phase I: MK-3475 + MLA Dose Level 1 | Experimental | MK-3475 will be given at 100 mg intravenously (IV) every 3 weeks starting no more than 1 week after MLA until progression or unacceptable toxicity. Receives: Biological: MK-3475; Device: MRI-guided laser ablation |
| Phase I: MK-3475 + MLA Dose Level 2 | Experimental | MK-3475 will be given at 150 mg intravenously (IV) every 3 weeks starting no more than 1 week after MLA until progression or unacceptable toxicity. Receives: Biological: MK-3475; Device: MRI-guided laser ablation |
| Phase I: MK-3475 + MLA Dose Level 3 | Experimental | MK-3475 will be given at 200 mg intravenously (IV) every 3 weeks starting no more than 1 week after MLA until progression or unacceptable toxicity. Receives: Biological: MK-3475; Device: MRI-guided laser ablation |
| Phase II: MK-3475 + MLA | Experimental | MK-3475 will be given at 200 mg intravenously (IV) every 3 weeks no more than 1 week after MLA, or no more than 1 week after biopsy (if no surgical debulking). This dose was determined in the Phase I portion of the trial. Receives: Biological: MK-3475; Device: MRI-guided laser ablation |
| Phase II: MK-3475 Only | Experimental | MK-3475 will be given at 200 mg intravenously (IV) every 3 weeks beginning 3 weeks after surgical debulking or no more than 1 week after biopsy (if no surgical debulking). This dose was determined in the Phase I portion of the trial. Receives: Biological: MK-3475 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximum Tolerated Dose (MTD) of MK-3475 When Combined With MLA - Phase I Only
The MTD is defined as the dose level immediately below the dose level at which 2 patients of a cohort (of 2 to 6 patients) experienced dose-limiting toxicity during the first cycle. Dose escalations will proceed until the MTD has been reached, or failing that, 200 mg of MK-3475 every 3 weeks will be considered the MTD.
Measured: Completion of Cycle 1 (each cycle is 3 weeks)
Progression-free Survival (PFS) - Phase II Only
PFS is defined as the duration of time from start of treatment to time of progression or death, whichever occurs first.
Measured: Through completion of follow-up (median length of follow-up 338 days, full range 43-2468 days).
Secondary outcomes (7)
Toxicity Profile of MK-3475 in Combination With MLA - Phase I Only
- The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for all toxicity reporting
- The only toxicities that will not be collected are those that are clearly related to MLA and/or surgery AND ALSO not related to MK-3475
- Adverse events will be tracked from start of treatment through 30 days following the last day of study treatment. Serious adverse events will be tracked for 90 days following the last dose of study treatment.
Measured: Through 90 days after completion of treatment (up to 168 weeks)
Overall Survival (OS) - Phase II Only
OS is defined as the duration of time from start of treatment to time of death.
Measured: Through completion of follow-up (median length of follow-up 338 days, full range 43-2468 days).
Anti-glioma Immune Response Before and After MK-3475 With MLA - Phase II Only
Measured: Up to 26 months
Correlate Intratumoral Expression of PD-L1 and the Frequency of Glioma Cell-specific Cytotoxic T Cells With PFS - Phase II Only
Measured: 6 months
Correlate Intratumoral Expression of PD-L1 and the Frequency of Glioma Cell-specific Cytotoxic T Cells With OS - Phase II Only
Measured: Up to 2 years after completion of treatment (estimated to be up to 272 weeks)
Identify PD-1-dependent Biomarkers in Glioma Cell-specific T Cells That Negatively Correlate With the Frequency of Glioma Cell-specific Cytotoxic T Cells and PFS - Phase II Only
Measured: Up to 2 years after completion of treatment (estimated to be up to 272 weeks)
Identify PD-1-dependent Biomarkers in Glioma Cell-specific T Cells That Negatively Correlate With the Frequency of Glioma Cell-specific Cytotoxic T Cells and OS - Phase II Only
Measured: Up to 2 years after completion of treatment (estimated to be up to 272 weeks)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Dec 2014 (estimated)
- Study start5 Aug 2015
- Primary completion15 Apr 2024
- Study completion15 Apr 2024
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.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Malignant GliomaStudies of the same condition, open and under way.
- More trials run by Washington University School of MedicineThe 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 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- As of Amendment 12, patients enrolled in the phase II portion of this trial will no longer be randomized. These patients will undergo MLA followed by MK-3475 treatment.
- Masking
- None (open label)
- Enrolment
- 55 participants (actual)
Sponsor and investigators
- Lead sponsor
- Washington University School of Medicine
- Sponsor type
- University, hospital or other
- Collaborators
- Merck Sharp & Dohme LLC
- Responsible party
- Sponsor
- Investigators
- Milan G Chheda, M.D., Principal investigator, Washington University School of Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02311582
- Sponsor's protocol ID
- 201501072
- Status last verified
- May 2025
- First submitted
- 4 Dec 2014
- Last updated
- 29 May 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- Yes
- Individual data sharing
- No
Publications
Campian JL, Le SB, Ghiaseddin A, Butt OH, Manektalia H, Chen D, Xu Y, Liu J, Rahman M, Thai N, Leidig WA, Johanns T, Ansstas G, Zhou AY, Pugazenthi S, Dunn GP, Huang J, Chheda MG, Kim AH, Leuthardt EC, Tran DD. Laser interstitial thermal therapy and adjuvant pembrolizumab in recurrent high-grade astrocytoma: a Phase 1/randomized Phase 2b trial. Nat Commun. 2026 Feb 26;17(1):1763. doi: 10.1038/s41467-026-69522-w.
PubMed 41748622Hwang H, Huang J, Khaddour K, Butt OH, Ansstas G, Chen J, Katumba RG, Kim AH, Leuthardt EC, Campian JL. Prolonged response of recurrent IDH-wild-type glioblastoma to laser interstitial thermal therapy with pembrolizumab. CNS Oncol. 2022 Mar 1;11(1):CNS81. doi: 10.2217/cns-2021-0013. Epub 2022 Jan 19.
PubMed 35043686
Study at a glance
From the registry record, last updated by the sponsor on 29 May 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I/II Study Testing the Safety, Toxicities, and Efficacy of MK-3475 in Combination With MRI-guided Laser Ablation in Recurrent Malignant Gliomas
- ClinicalTrials.gov ID
- NCT02311582
- Acronym / sponsor ID
- 201501072
- Conditions
- Malignant Glioma
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 55 participants (actual)
- Lead sponsor
- Washington University School of MedicineUniversity, hospital or other
- Collaborators
- Merck Sharp & Dohme LLC
- Study start
- 5 Aug 2015 (actual)
- Primary completion
- 15 Apr 2024 (actual)
- Study completion
- 15 Apr 2024 (actual)
- First posted
- 8 Dec 2014 (estimated)
- Results
- Posted 29 May 2025
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The blood brain barrier (BBB) is a major obstacle to drug delivery in the treatment of malignant brain tumors including glioblastoma multiforme (GBM). MRI-guided laser ablation (MLA) has been noted to disrupt peritumoral the blood brain barrier (BBB), which may then lead to increased access of new tumor antigens to the lymphovascular system and vice versa of immune effector cells to the tumor for effective activation of the immune system, and tumor infiltration, respectively. Therefore, the combination of MK-3475 and MLA as proposed in this protocol is hypothesized to create a therapeutic combinatorial effect in which MLA increases material access to promote immune activation and then MK-3475 maximizes these tumor-specific immune reactions to impart effective tumor control.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 5
- Model description
- As of Amendment 12, patients enrolled in the phase II portion of this trial will no longer be randomized. These patients will undergo MLA followed by MK-3475 treatment.
| Arm | Type | Receives |
|---|---|---|
| Phase I: MK-3475 + MLA Dose Level 1 | Experimental | Biological: MK-3475, Device: MRI-guided laser ablationMK-3475 will be given at 100 mg intravenously (IV) every 3 weeks starting no more than 1 week after MLA until progression or unacceptable toxicity. |
| Phase I: MK-3475 + MLA Dose Level 2 | Experimental | Biological: MK-3475, Device: MRI-guided laser ablationMK-3475 will be given at 150 mg intravenously (IV) every 3 weeks starting no more than 1 week after MLA until progression or unacceptable toxicity. |
| Phase I: MK-3475 + MLA Dose Level 3 | Experimental | Biological: MK-3475, Device: MRI-guided laser ablationMK-3475 will be given at 200 mg intravenously (IV) every 3 weeks starting no more than 1 week after MLA until progression or unacceptable toxicity. |
| Phase II: MK-3475 + MLA | Experimental | Biological: MK-3475, Device: MRI-guided laser ablationMK-3475 will be given at 200 mg intravenously (IV) every 3 weeks no more than 1 week after MLA, or no more than 1 week after biopsy (if no surgical debulking). This dose was determined in the Phase I portion of the trial. |
| Phase II: MK-3475 Only | Experimental | Biological: MK-3475MK-3475 will be given at 200 mg intravenously (IV) every 3 weeks beginning 3 weeks after surgical debulking or no more than 1 week after biopsy (if no surgical debulking). This dose was determined in the Phase I portion of the trial. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (23 listed)
- Phase I: Histologically confirmed grade III or IV malignant glioma.
- Phase II: Histologically confirmed grade IV malignant glioma (GBM).
- Note: GBM variants and suspected secondary GBM are allowed for both phase I and phase II.
- Unequivocal evidence of tumor progression as documented by biopsy or brain MRI scan per RANO criteria.
- There must be an interval of at least 12 weeks from the completion of standard front-line therapy to study registration unless there is unequivocal evidence for tumor recurrence per RANO criteria. When the interval is less than 12 weeks, the use of perfusion imaging and/or PET scan is allowed to differentiate between unequivocal evidence of tumor recurrence and pseudoprogression. Standard front-line therapy is as described below:
Key exclusion criteria (25 listed)
- Prior treatment with any anti-angiogenic agent (including bevacizumab).
- Prior treatment with an anti-PD-1, anti-PD-L1, anti-PD-L2, or 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).
- Prior treatment with a monoclonal antibody within 4 weeks prior to the first dose of MK-3475 or has not recovered (i.e. ≤ grade 1 or at baseline) from adverse events due to agents administered more than 4 weeks earlier.
- Prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to the first dose of MK-3475 or has not recovered (i.e. ≤ grade 1 or at baseline) from adverse events due to a previously administered agent.
- Candidates for curative resection or urgent surgical procedure(s) needed.
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 |
|---|---|---|
| MK-3475Also: Pembrolizumab, KeytrudaPatients currently on pembrolizumab beyond the 2 year/35 cycle limit at the time of the approval of Amendment 13 (approved 07/28/2021) may continue to receive pembrolizumab unless there is progression, toxicity or agreement by the patient and PI to come off therapy. Participants who discontinue pembrolizumab after receiving 35 doses are eligible for retreatment with pembrolizumab if they progress during follow-up provided they meet the requirements. Participants may receive an additional 17 cycles (12 months) of pembrolizumab during the Second Course Phase (Retreatment). | Biological | Phase I: MK-3475 + MLA Dose Level 1, Phase I: MK-3475 + MLA Dose Level 2, Phase I: MK-3475 + MLA Dose Level 3, Phase II: MK-3475 + MLA, Phase II: MK-3475 Only |
| MRI-guided laser ablationAlso: MLA, NeuroBlate, AutoLITTMLA is a minimally invasive laser surgery, which employs a small incision in the scalp and skull, through which a thin laser probe is inserted and guided by MR imaging to the core of the tumor mass where it delivers hyperthermic ablation from the core to the rim. | Device | Phase I: MK-3475 + MLA Dose Level 1, Phase I: MK-3475 + MLA Dose Level 2, Phase I: MK-3475 + MLA Dose Level 3, Phase II: MK-3475 + MLA |
Primary outcome
Maximum Tolerated Dose (MTD) of MK-3475 When Combined With MLA - Phase I Only
Time frame: Completion of Cycle 1 (each cycle is 3 weeks)
The MTD is defined as the dose level immediately below the dose level at which 2 patients of a cohort (of 2 to 6 patients) experienced dose-limiting toxicity during the first cycle. Dose escalations will proceed until the MTD has been reached, or failing that, 200 mg of MK-3475 every 3 weeks will be considered the MTD.
Progression-free Survival (PFS) - Phase II Only
Time frame: Through completion of follow-up (median length of follow-up 338 days, full range 43-2468 days).
PFS is defined as the duration of time from start of treatment to time of progression or death, whichever occurs first.
7 secondary outcomes
Toxicity Profile of MK-3475 in Combination With MLA - Phase I Only
Time frame: Through 90 days after completion of treatment (up to 168 weeks)
Overall Survival (OS) - Phase II Only
Time frame: Through completion of follow-up (median length of follow-up 338 days, full range 43-2468 days).
Anti-glioma Immune Response Before and After MK-3475 With MLA - Phase II Only
Time frame: Up to 26 months
Correlate Intratumoral Expression of PD-L1 and the Frequency of Glioma Cell-specific Cytotoxic T Cells With PFS - Phase II Only
Time frame: 6 months
Correlate Intratumoral Expression of PD-L1 and the Frequency of Glioma Cell-specific Cytotoxic T Cells With OS - Phase II Only
Time frame: Up to 2 years after completion of treatment (estimated to be up to 272 weeks)
Identify PD-1-dependent Biomarkers in Glioma Cell-specific T Cells That Negatively Correlate With the Frequency of Glioma Cell-specific Cytotoxic T Cells and PFS - Phase II Only
Time frame: Up to 2 years after completion of treatment (estimated to be up to 272 weeks)
Identify PD-1-dependent Biomarkers in Glioma Cell-specific T Cells That Negatively Correlate With the Frequency of Glioma Cell-specific Cytotoxic T Cells and OS - Phase II Only
Time frame: Up to 2 years after completion of treatment (estimated to be up to 272 weeks)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 May 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 41748622Campian JL, Le SB, Ghiaseddin A, Butt OH, Manektalia H, Chen D, Xu Y, Liu J, Rahman M, Thai N, Leidig WA, Johanns T, Ansstas G, Zhou AY, Pugazenthi S, Dunn GP, Huang J, Chheda MG, Kim AH, Leuthardt EC, Tran DD. Laser interstitial thermal therapy and adjuvant pembrolizumab in recurrent high-grade astrocytoma: a Phase 1/randomized Phase 2b trial. Nat Commun. 2026 Feb 26;17(1):1763. doi: 10.1038/s41467-026-69522-w.
- Derived from this study: PubMed 35043686Hwang H, Huang J, Khaddour K, Butt OH, Ansstas G, Chen J, Katumba RG, Kim AH, Leuthardt EC, Campian JL. Prolonged response of recurrent IDH-wild-type glioblastoma to laser interstitial thermal therapy with pembrolizumab. CNS Oncol. 2022 Mar 1;11(1):CNS81. doi: 10.2217/cns-2021-0013. Epub 2022 Jan 19.
- Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of MedicineLink provided by the sponsor.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Milan G Chheda, M.D. principal investigator
Washington University School of Medicine
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing MK-3475 and MRI-guided laser ablation in people with Malignant Glioma, run by Washington University School of Medicine at 2 sites 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 23 inclusion and 25 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 29 May 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites 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 combined 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.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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 29 May 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) of MK-3475 When Combined With MLA - Phase I Only (time frame: Completion of Cycle 1 (each cycle is 3 weeks)). 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?
On the ClinicalTrials.gov record for NCT02311582, which also lists 2 linked publications.
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 29 May 2025.