Pembrolizumab in Treating Patients With Recurrent Glioblastoma

NCT02337686 | Active Not Recruiting Phase 2 Results FDA Drug

• 2 other identifiers: 2014-0820NCI-2015-00174
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

Brief 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 and spread.

Conditions

Recurrent Glioblastoma; Recurrent Gliosarcoma

Outcome Measures

Primary Outcomes (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.

  At 6 months

Secondary Outcomes (4)

• Number of Participants With Progression

  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

• Overall Survival

  Up to 2 years

• Number of Participants With Response Rate

  Up to 2 years

• Number of Adverse Events

  Up to 30 days after completion of study treatment

Study Arms (1)

Treatment (pembrolizumab, surgery)

EXPERIMENTAL

Patients 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.

Other: Laboratory Biomarker Analysis; Biological: Pembrolizumab; Other: Pharmacological Study; Procedure: Therapeutic Conventional Surgery

Interventions

Laboratory Biomarker Analysis OTHER

Correlative studies

Treatment (pembrolizumab, surgery)

Pembrolizumab BIOLOGICAL

Given IV

Also known as: Keytruda, Lambrolizumab, MK-3475, SCH 900475

Treatment (pembrolizumab, surgery)

Pharmacological Study OTHER

Correlative studies

Treatment (pembrolizumab, surgery)

Therapeutic Conventional Surgery PROCEDURE

Undergo surgery

Treatment (pembrolizumab, surgery)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)
• 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)

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

M D Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Publications (1)

• 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.

  PMID: 31755915 RESULT

Related Links

• MD Anderson Cancer Center

MeSH Terms

Conditions

Glioblastoma; Gliosarcoma

Interventions

pembrolizumab

Condition Hierarchy (Ancestors)

Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Results Point of Contact

• Title: Dr. Vinaykumar Puduvalli, MD-Chair, Neuro-Oncology
• Organization: UT MD Anderson Cancer Center

vpuduval@mdanderson.org

(713) 745-2343

Study Officials

• Vinay Puduvalli, MD

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 8, 2015
• First Posted: January 14, 2015
• Study Start: April 28, 2015
• Primary Completion: May 24, 2017
• Study Completion (Estimated): December 31, 2026
• Last Updated: August 15, 2025
• Results First Posted: January 11, 2023

Record last verified: 2025-08

Locations

US (1)