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Recurrent GlioblastomaPhase 2NCT02337686

Pembrolizumab in Treating Patients With Recurrent Glioblastoma

A Phase 2 study testing Laboratory Biomarker Analysis, Pembrolizumab and Pharmacological Study in people with Recurrent Glioblastoma and Recurrent Gliosarcoma, run by M.D. Anderson Cancer Center at 1 site in United States.

Active, not recruiting

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

Official record
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Trial summary

This phase II trial studies the effects of pembrolizumab on the body, or pharmacodynamics, in patients with glioblastoma that has come back. Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow… Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Recurrent Glioblastoma, Recurrent Gliosarcoma
What is being tested?
Laboratory Biomarker Analysis, Pembrolizumab and Pharmacological Study
Could I receive a placebo?
No, everyone receives an active treatment
How many people
18 participants
Where
1 siteUnited States
Study dates
28 Apr 2015to 31 Dec 2026
Phase
Phase 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

  • Be willing and able to provide written informed consent/assent for the trial
  • 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
  • Patients must be at first or second relapse and clinically require reoperation for tumor progression within 4 to 6 weeks; Note: relapse is defined as progression following initial therapy (i.e., radiation, chemotherapy, or radiation + chemotherapy); if the participant had a surgical resection for relapsed disease and no anti-tumor therapy instituted for up to 12 weeks, this is considered one relapse; for participants who had prior therapy for a low grade glioma, the surgical diagnosis of a high grade glioma will be considered first relapse
  • Have measurable disease consisting of a minimal volume of 1 cm^3
  • Have provided tissue from an archival tissue sample or newly obtained core or excisional biopsy of a tumor lesion
  • Have a performance status of >= 60 on the Karnofsky performance scale (KPS)
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  • Stable dose of steroids for 5 days, no more than 2 mg dexamethasone (or equivalent) total per day
  • Absolute neutrophil count (ANC) >= 1,500/mcL (performed within 14 days prior to registration)
  • Platelets >=100,000/mcL (performed within 14 days prior to registration)
  • Hemoglobin >= 9 g/dL or >= 5.6 mmol/L (performed within 14 days prior to registration)
  • Serum creatinine =< 1.5 X upper limit of normal (ULN) OR measured or calculated creatinine clearance (glomerular filtration rate [GFR] can also be used in place of creatinine or creatinine clearance [CrCl]) >= 60 mL/min for subject with creatinine levels > 1.5 X institutional ULN (performed within 14 days prior to registration)
  • Serum total bilirubin =< 1.5 X ULN OR direct bilirubin =< ULN for subjects with total bilirubin levels > 1.5 ULN (performed within 14 days prior to registration)
  • Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT]) and alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 X ULN OR =< 5 X ULN for subjects with liver metastases (performed within 14 days prior to registration)
  • International normalized ratio (INR) or prothrombin time (PT) =< 1.5 X ULN unless subject is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants (performed within 14 days prior to registration)
  • Activated partial thromboplastin time (aPTT) =< 1.5 X ULN unless subject is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants (performed within 14 days prior to registration)
  • Female subject of childbearing potential should have a negative serum pregnancy test
  • Female subjects of childbearing potential should be willing to use 2 methods of birth control or be surgically sterile, or abstain from heterosexual activity for the course of the study through 120 days after the last dose of study medication; subjects of childbearing potential are those who have not been surgically sterilized or have not been free from menses for > 1 year
  • Male subjects should agree to use an adequate method of contraception starting with the first dose of study therapy through 120 days after the last dose of study therapy

Who cannot join

  • Has been treated previously with bevacizumab
  • Has tumor localized primarily to the brainstem or spinal cord
  • Has received prior interstitial brachytherapy, implanted chemotherapy, or therapeutics delivered by local injection or convection enhanced delivery
  • Is currently participating in or has participated in a study of an investigational agent or using an investigational device 4 weeks since last dose of agent administration
  • Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy > 2 mg of dexamethasone total per day or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment
  • Has had a prior monoclonal antibody 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
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  • 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: subjects with alopecia, =< grade 2 neuropathy are an exception to this criterion and may qualify for the study
  • Has a known additional malignancy that is progressing or requires active treatment; 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 known carcinomatous meningitis, extracranial disease, or multifocal disease
  • 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 systemic steroids or immunosuppressive agents; 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 would not be excluded from the study; subjects with hypothyroidism stable on hormone replacement or Sjogren's syndrome will not be excluded from the study
  • Has evidence of interstitial lung disease or 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
  • 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 screening visit through 120 days after the last dose of trial treatment
  • Has received prior therapy with an anti-programmed cell death (PD)-1, anti-PD ligand (PD-L)1, anti-PD-L2, anti-cluster of differentiation (CD)137 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); testing not required
  • Has known history of hepatitis B (e.g., hepatitis B surface antigen [HBsAg] reactive) or hepatitis C (e.g., hepatitis C virus [HCV] ribonucleic acid [RNA] [qualitative] is detected); testing not required
  • Has received a live vaccine within 30 days prior to the first dose of trial treatment

Trial locations and contacts

1 site in 1 country.

United States1 site
  • M D Anderson Cancer Center

    Houston, Texas, 77030

Other trials in United States

About this study

Official title: Pharmacodynamic Study of Pembrolizumab in Patients With Recurrent Glioblastoma

This phase II trial studies the effects of pembrolizumab on the body, or pharmacodynamics, in patients with glioblastoma that has come back. Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread.

Read the detailed description

PRIMARY OBJECTIVES:

  1. To evaluate immune effector function in resected glioblastoma tissue after treatment with intravenously administered pembrolizumab monotherapy in the neoadjuvant setting in patients with recurrent glioblastoma.

II. To correlate the progression free survival at 6 months (PFS6) with objective increases in the immune effector T cell: regulatory T cell (Treg) ratio in tumor tissue as measured by ex vivo T-cell-specific cytokines profiling.

SECONDARY OBJECTIVES:

  1. Comparison of time to progression of last prior therapy to time to progression on pembrolizumab, median duration of response, overall response rate (ORR), and overall survival (OS) and safety.

TERTIARY OBJECTIVES:

  1. To identify imaging characteristics associated with immunological changes in tumor following treatment with pembrolizumab.

OUTLINE:

Patients receive pembrolizumab intravenously (IV) over 30 minutes on day -21 and day -1, and then undergo surgery on day 0. After 2-3 weeks or recovery from surgery, patients continue to receive pembrolizumab IV over 30 minutes every 3 weeks. Courses repeat every 42 days for up to 24 months in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 3 months.

Being tested
Laboratory Biomarker Analysis, Pembrolizumab, Pharmacological Study, Therapeutic Conventional Surgery
Medical subject headings
Glioblastoma, Gliosarcoma

What participants receive

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

Study groups in NCT02337686
Study groupRoleWhat they receive
Treatment (pembrolizumab, surgery)ExperimentalPatients receive pembrolizumab IV over 30 minutes on day -21 and day -1, and then undergo surgery on day 0. After 2-3 weeks or recovery from surgery, patients continue to receive pembrolizumab IV over 30 minutes every 3 weeks. Courses repeat every 42 days for up to 24 months in the absence of disease progression or unacceptable toxicity.
Receives: Other: Laboratory Biomarker Analysis; Biological: Pembrolizumab; Other: Pharmacological Study; Procedure: Therapeutic Conventional Surgery

What is being measured

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

  1. Number of Participants With Progression Free Survival at 6 Months

    Progression-free survival, defined as the time from study enrollment until the time of first occurrence of disease progression, relapse, or death due to disease. Patients who are alive without progression or relapse will be censored at the time of last contact. Response Assessment in Neuro-Oncology (RANO) Criteria for Evaluating Response.

    Measured: At 6 months

Secondary outcomes (4)
  1. Number of Participants With Progression

    Defined as the length of time from the date of diagnosis or the start of treatment for a disease until the disease starts to get worse or spread to other parts of the body. Time to Progression measured by the method of Kaplan and Meier.

    Measured: The time from study enrollment until the time of first occurrence of disease progression, relapse, or death due to disease, assessed up to 2 years

  2. Overall Survival

    Overall survival time is defined as the time from registration to death due to any cause. The distribution of survival time will be estimated using the method of Kaplan-Meier.

    Measured: Up to 2 years

  3. Number of Participants With Response Rate

    Logistic regression will be utilized to assess the effect of patient prognostic factors on the response rate. Per the Response Assessment in Neuro-Oncology (RANO) Criteria for Evaluating Response for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=50% decrease in the sum of the products of perpendicular diameter of measurable lesions; Overall Response (OR) = CR + PR.

    Measured: Up to 2 years

  4. Number of Adverse Events

    Adverse events as defined by the Common Terminology Criteria for Adverse Events (CTCAE) version 4 for grades 1, 2, and 3. There were no grade 4 AEs.

    Measured: Up to 30 days after completion of study treatment

Timeline

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

  1. First posted14 Jan 2015 (estimated)
  2. Study start28 Apr 2015
  3. Primary completion24 May 2017
  4. Study completion31 Dec 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 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
18 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02337686
Sponsor's protocol ID
2014-0820
Other IDs
NCI-2015-00174, 2014-0820
Status last verified
Aug 2026
First submitted
8 Jan 2015
Last updated
3 Sep 2026
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No

Publications

  • de Groot J, Penas-Prado M, Alfaro-Munoz K, Hunter K, Pei BL, O'Brien B, Weathers SP, Loghin M, Kamiya Matsouka C, Yung WKA, Mandel J, Wu J, Yuan Y, Zhou S, Fuller GN, Huse J, Rao G, Weinberg JS, Prabhu SS, McCutcheon IE, Lang FF, Ferguson SD, Sawaya R, Colen R, Yadav SS, Blando J, Vence L, Allison J, Sharma P, Heimberger AB. Window-of-opportunity clinical trial of pembrolizumab in patients with recurrent glioblastoma reveals predominance of immune-suppressive macrophages. Neuro Oncol. 2020 Apr 15;22(4):539-549. doi: 10.1093/neuonc/noz185.

    PubMed 31755915

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Laboratory Biomarker Analysis, Pembrolizumab and Pharmacological Study in people with Recurrent Glioblastoma and Recurrent Gliosarcoma, run by M.D. Anderson Cancer Center 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 18 inclusion and 19 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 3 Sep 2026. 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 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 11 Jan 2023). 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?

Number of Participants With Progression Free Survival at 6 Months (time frame: At 6 months). 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 NCT02337686, 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 3 Sep 2026.

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