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AzTrials

Brain CancerPhase 1NCT02852655

A Pilot Surgical Trial To Evaluate Early Immunologic Pharmacodynamic Parameters For The PD-1 Checkpoint Inhibitor, Pembrolizumab (MK-3475), In Patients With Surgically Accessible Recurrent/Progressive Glioblastoma

A Phase 1 study testing MK-3475 in people with Brain Cancer, run by Dana-Farber Cancer Institute at 7 sites in United States.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
Search all trials

Trial summary

This research study is studying an immunotherapy as a possible treatment for Glioblastoma. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Brain Cancer
What is being tested?
MK-3475
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
60 participants
Where
7 sitesUnited States
Study dates
21 Sep 2016to 31 Jul 2026
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

  • Have histologically confirmed World Health Organization Grade IV malignant glioma (glioblastoma or gliosarcoma). Participants will be eligible if the original histology was low-grade glioma and a subsequent histological diagnosis of glioblastoma or variants is made.
  • Be willing and able to provide written informed consent/assent for the trial.
  • Be 18 years of age on day of signing informed consent.
  • Have a Karnofsky performance status (KPS) ≥ 70 (Appendix A).
  • Previous first line therapy with at least radiotherapy.
  • Be at first or second relapse. Note: Relapse is defined as progression following initial therapy (i.e., radiation ± chemotherapy). For participants who had prior therapy for a low-grade glioma, the surgical diagnosis of a high-grade glioma will be considered the first relapse.
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  • Participants must have shown unequivocal evidence for tumor progression by MRI or CT scan.
  • Demonstrate adequate organ function as defined in Table 1, all screening labs should be performed within 14 days of registration.
  • Table 1 Adequate Organ Function Laboratory Values
  • System Laboratory Value
  • Hematological
  • Absolute neutrophil count (ANC) ≥1,500 /mcL
  • Platelets ≥100,000 / mcL
  • Hemoglobin ≥9 g/dL or ≥5.6 mmol/L without transfusion or EPO dependency (within 7 days of assessment)
  • Renal
  • Serum creatinine OR Measured or calculated creatinine clearance (GFR can also be used in place of creatinine or CrCl) ≤1.5 X institutional upper limit of normal (ULN) OR ≥60 mL/min for subject with creatinine levels > 1.5 X institutional ULN Hepatic
  • Serum total bilirubin ≤ 1.5 X institutional ULN OR Direct bilirubin ≤ institutional ULN for subjects with total bilirubin levels > 1.5 institutional ULN
  • AST (SGOT) and ALT (SGPT) ≤ 2.5 X institutional ULN OR ≤ 5 X institutional ULN for subjects with Gilberts syndrome
  • Albumin >2.5 mg/dL
  • Coagulation
  • International Normalized Ratio (INR) or Prothrombin Time (PT)
  • Activated Partial Thromboplastin Time (aPTT) ≤1.5 X institutional ULN unless subject is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants
  • ≤1.5 X institutional ULN unless subject is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants
  • Creatinine clearance should be calculated per institutional standard.
  • CT or MRI within 14 days prior of registration.
  • An interval of at least 4 weeks (to registration) between prior surgical resection or one week for stereotactic biopsy.
  • An interval of at least 12 weeks from the completion of radiation therapy to registration unless there is unequivocal histologic confirmation of tumor progression.
  • Participants must have recovered to grade 0 or 1 or pre-treatment baseline from clinically significant toxic effects of prior therapy (including but not limited to exceptions of alopecia, laboratory values listed per inclusion criteria, and lymphopenia which is common after therapy with temozolomide).
  • From registration, the following time periods must have elapsed: 5 half-lives from any investigational agent, 4 weeks from cytotoxic therapy (except 23 days for temozolomide and 6 weeks from nitrosoureas), 6 weeks from antibodies, or 4 weeks (or 5 half-lives, whichever is shorter) from other anti-tumor therapies (including vaccines). No wash-out period required from TTF.
  • Participants must have sufficient tissue from prior surgery revealing glioblastoma or variants for submission following registration. The following amount of tissue is required:
  • 1 formalin-fixed paraffin-embedded (FFPE) tumor tissue block (preferred) OR
  • 10 FFPE unstained slides (5 μm thick)
  • Patients must be undergoing surgery that is clinically indicated as determined by their care providers. Patients must be eligible for surgical resection with the expectation that the surgeon is able to resect at least 400mg of tumor with low risk of inducing neurological injury.
  • Female subject of childbearing potential must have a negative urine or serum pregnancy within 72 hours prior to registration. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required. Women are considered post-menopausal and not of child bearing potential if they have had 12 months of natural (spontaneous) amenorrhea with an appropriate clinical profile (e.g., age appropriate, history of vasomotor symptoms) or six months of spontaneous amenorrhea with serum FSH levels > 40 mIU/mL and estradiol < 20 pg/mL or have had surgical bilateral oophorectomy (with or without hysterectomy) at least six weeks ago. In the case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment is she considered not of child bearing potential.
  • Women of child-bearing potential (WOCBP), defined as all women physiologically capable of becoming pregnant, must agree to use highly effective contraception during study treatment and for 120 days after study discontinuation. Highly effective contraception is defined as either:
  • True Abstinence: When this is in line with the preferred and usual lifestyle of the subject. Periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception.
  • Sterilization: Surgical bilateral oophorectomy (with or without hysterectomy) or tubal ligation at least six weeks ago. In case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment (as described in item 3.1.16 above).
  • Male Partner Sterilization (with the appropriate post-vasectomy documentation of the absence of sperm in the ejaculate). For female subjects on the study, the vasectomised male partner must be the sole partner for that participant.
  • Use of a combination of any two of the following:
  • Placement of an intrauterine device (IUD) or intrauterine system (IUS)
  • Barrier methods of contraception: Condom or Occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/vaginal suppository
  • Appropriate hormonal contraceptives (including any registered and marketed contraceptive agent that contains an estrogen and/or a progestational agent - including oral, subcutaneous, intrauterine, or intramuscular agents)
  • Male subjects must agree to use adequate method of contraception starting with the first dose of study therapy through 120 days after the last dose of therapy.

Who cannot join

  • Current or planned participation in a study of an investigational agent or using an investigational device.
  • Has a diagnosis of immunodeficiency.
  • Has tumor primarily localized to the brainstem or spinal cord.
  • Has presence of diffuse leptomeningeal disease or extracranial disease.
  • Has received systemic immunosuppressive treatments, aside from systemic corticosteroids (such as methotrexate, chloroquine, azathioprine, etc) within six months of registration.
  • Has received anti-angiogenic or anti-VEGF targeted agents (e.g. bevacizumab, cediranib, aflibercept, vandetanib, XL-184, sunitinib, etc).
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  • Requires treatment with high dose systemic corticosteroids defined as dexamethasone > 4 mg/day or bioequivalent for at least 3 consecutive days within 2 weeks of registration.
  • Has received prior interstitial brachytherapy, implanted chemotherapy, stereotactic radiosurgery or therapeutics delivered by local injection or convection enhanced delivery.
  • Has history of known coagulopathy that increases risk of bleeding or a history of clinically significant hemorrhage within 12 months of registration.
  • Has a known history of active TB (Bacillus Tuberculosis).
  • Has gastrointestinal bleeding or any other hemorrhage/bleeding event CTCAE Grade > 3 within 6 months of registration.
  • Has a known additional malignancy that is progressing or requires active treatment within 3 years of registration. 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.
  • 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 (eg., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.
  • Has known history of, or any evidence of active non-infectious pneumonitis.
  • Has an active infection requiring systemic therapy.
  • 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 but are not limited to symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia or psychiatric illness/social situations that would limit compliance with study requirements.
  • Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
  • 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).
  • 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 prior to registration.
  • Has a known hypersensitivity to any of the study therapy products.

Trial locations and contacts

7 sites in 1 country.

7 sites in 1 country

United States7 sites

  • Massachusetts General Hospital

    Boston, Massachusetts, 02114

  • Dana Farber Cancer Institute

    Boston, Massachusetts, 02115

  • UT, MD Anderson Cancer Center

    Houston, Texas, 77030

  • University of California, Los Angeles

    Los Angeles, California, 90095

  • Memorial Sloan-Kettering Cancer

    New York, New York, 10065

  • Huntsman Cancer Institute

    Salt Lake City, Utah, 84112

  • University of California, San Francisco

    San Francisco, California, 94143-0372

Other trials in United States

About this study

This research study is studying an immunotherapy as a possible treatment for Glioblastoma.

Read the detailed description

PD-1 works to help tumor cells continue to grow and multiply. Pembrolizumab (MK-3475) is a humanized monoclonal antibody. Humanized monoclonal is an antibody that is designed to block the action of the receptor, PD-1.

The FDA (the U.S. Food and Drug Administration) has not approved Pembrolizumab for Glioblastoma but it has been approved for other uses.

Conditions
Brain Cancer
Being tested
MK-3475
Keywords
Brain Tumor
Medical subject headings
Brain Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • MK-3475Drug

    Also called Pembrolizumab

Study groups in NCT02852655
Study groupRoleWhat they receive
Pre-surgery MK-3475Experimental-After a screening phase of 14 days, eligible subjects will be randomized into two groups. * Pembrolizumab (MK3475) pre-surgery at pre-determine dosage followed by Pembrolizumab at pre-determine dosage every 3 weeks post surgery. * MK-3475 will be administered intravenously
Receives: Drug: MK-3475
No MK-3475 at Pre-SurgeryActive comparator-After a screening phase of 14 days, eligible subjects will be randomized into two groups. * Pembrolizumab (MK-3475) at pre-determine dosage every 3 weeks post surgery. * MK-3475 will be administered intravenously
Receives: Drug: MK-3475

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Tumor Infiltrating T Lymphocyte (TIL) Density

    To measure changes in tumor infiltrating T lymphocyte (TIL) density, defined as % total cells. It will be assessed using pooled Group A and Group B patients.

    Measured: 2 weeks. TIL density is determined in surgical tumor tissue; on-study surgery occurs 14 days (+/- 5 days) after Neoadjuvant Day 1.

  2. Cell Cycle and Cancer Proliferation Genetic Signature

    To measure changes in cell cycle and cancer proliferation genetic signature; these results are reported using Gene Set Variation Analysis (GSVA) absolute enrichment scores (ES). GSVA scores are unit-less scores derived by comparing mRNA expression of a specific gene set to genes outside of the gene set in a sample. In this case, GSVA scores for "Farmers_breast_cancer_cluster_2, as previously described" were utilized.

    PMID 30742122 (https://pubmed.ncbi.nlm.nih.gov/30742122/) and PMID 23323831 (https://pubmed.ncbi.nlm.nih.gov/23323831/)

    It will be assessed using pooled Group A and Group B patients.

    Measured: 2 weeks. Cell cycle/cancer proliferation genetic signature is determined in surgical tumor tissue; on-study surgery occurs 14 days (+/- 5 days) after Neoadjuvant Day 1.

  3. Incidence of Treatment-Emergent Adverse Events

    Number of Participants who Experienced a Serious Adverse Event (SAE) or Event of Clinical Interest (ECI) Deemed At Least Possibly Related to Pembrolizumab (MK3475). The following are measured as part of safety: laboratory safety assessments, KPS status, vital signs and physical examinations.

    Measured: 5 years. Although there is still 1 patient on active study treatment as of today (4/1/2024), we stopped looking at this information as of 6/2/2022 for study reporting purposes.

Secondary outcomes (1)

  1. Progression Free Survival (PFS)

    To determine the efficacy of pembrolizumab in patients with surgically accessible recurrent/progressive glioblastoma (GBM) participants as measured by 6-month progression-free survival (PFS6) using Radiologic Assessment in Neuro-Oncology (RANO) criteria.

    Progression is defined using RANO criteria, as any of the following:

    1. ≥ 25% increase in sum of the products of perpendicular diameters of enhancing lesions compared with the smallest tumor measurement, on stable or increasing doses of corticosteroids
    2. Any new enhancing measurable lesion
    3. Clear clinical deterioration not attributable to other causes apart from the tumor or changes in corticosteroid dose
    4. Or failure to return for evaluation as a result of death or deteriorating condition

    Measured: 180 Days

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted2 Aug 2016 (estimated)
  2. Study start21 Sep 2016
  3. Primary completion2 Jun 2022
  4. Study completion31 Jul 2026 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
60 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02852655
Sponsor's protocol ID
16-225
Status last verified
Mar 2026
First submitted
27 Jul 2016
Last updated
20 Mar 2026
Data monitoring committee
Yes
Individual data sharing
No

Publications

  • McFaline-Figueroa JR, Sun L, Youssef GC, Huang R, Li G, Kim J, Lee EQ, Nayak L, Chukwueke U, Beroukhim R, Batchelor TT, Chiocca EA, Everson RG, Doherty L, Stefanik J, Partridge K, Spearman A, Myers A, Westergaard C, Russ A, Lavallee M, Smokovich A, LaForest-Roys C, Garcia Fox R, McCluskey C, Bi WL, Arnaout O, Peruzzi P, Cosgrove GR, Ligon KL, Arrillaga-Romany I, Clarke JL, Reardon DA, Cloughesy TF, Prins RM, Wen PY. Neoadjuvant anti-PD1 immunotherapy for surgically accessible recurrent glioblastoma: clinical and molecular outcomes of a stage 2 single-arm expansion cohort. Nat Commun. 2024 Dec 30;15(1):10757. doi: 10.1038/s41467-024-54326-7.

    PubMed 39737895

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing MK-3475 in people with Brain Cancer, run by Dana-Farber Cancer Institute at 7 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 43 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: under way, not looking for participants, as of the sponsor's last update on 20 Mar 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 7 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 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 26 Nov 2024). 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?

Tumor Infiltrating T Lymphocyte (TIL) Density (time frame: 2 weeks. TIL density is determined in surgical tumor tissue; on-study surgery occurs 14 days (+/- 5 days) after Neoadjuvant Day 1.). The study lists 3 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 NCT02852655, which also lists 1 linked publication.

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 20 Mar 2026.

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