Radiation Therapy With Temozolomide and Pembrolizumab in Treating Patients With Newly Diagnosed Glioblastoma

NCT02530502 | Terminated Phase 1 DMC

• 4 other identifiers: NU 15C01NCI-2015-00736STU00200883P30CA060553
• Study Type: interventional
• Target: 4
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of phase I trial is to determine the safest, most effective dose of MK-3475 (pembrolizumab), when used with radiotherapy and temozolomide for treating newly diagnosed patients with glioblastoma (GBM). Temozolomide binds to the deoxyribonucleic acid (DNA), changes it, and triggers the death of tumor cells. MK-3475 is an investigational drug, it is not currently approved by the Federal Drug Administration (FDA) for use in treating GBM but it is approved for treating melanoma. MK-3475 works by targets the local tumor immune-protection in solid tumors. It is hoped the addition of MK-3475 to the usual treatment for GBM will improve the current treatment.

Conditions

Adult Glioblastoma

Outcome Measures

Primary Outcomes (1)

• The dose-limiting toxicity of Radiation Therapy With Temozolomide and Pembrolizumab will be evaluated

  Any dose-limiting toxicity (DLT) experienced during the first cycle (9 weeks) of study treatment, will be determined. The Maximum Tolerated Dose (MTD) will constitute the RP2D

  9 weeks

Secondary Outcomes (1)

• Toxicity of Pembrolizumab

  Up to 30 days after the last dose of study drug

Other Outcomes (5)

• Methylguanine-DNA methyltransferase (MGMT) status

  Baseline

• PDL1 expression in tumor

  Baseline

• Peripheral T-cell activation

  Up to 108 weeks (12 courses post-RT)

Study Arms (1)

Treatment (RT, temozolomide, pembrolizumab)

EXPERIMENTAL

RT PORTION: Patients undergo focal RT over 42 days, and receive concurrent temozolomide PO QD on days 1-42 and pembrolizumab IV over 30 minutes on days 1, 22, and 43. POST-RT: After completion of RT, patients receive temozolomide PO QD on days 1-5 and 29-34 of course 1 and days 1-5 and 29-33 of subsequent courses, and pembrolizumab IV over 30 minutes on days 1, 22, and 43. Treatment repeats every 9 weeks for up to 6 courses in the absence of disease progression or unacceptable toxicity. After 6 courses, patients deriving benefit may continue to receive pembrolizumab for an additional 12 months.

Other: Laboratory Biomarker Analysis; Biological: Pembrolizumab; Radiation: Radiation Therapy; Drug: Temozolomide

Interventions

Laboratory Biomarker Analysis OTHER

Correlative studies

Treatment (RT, temozolomide, pembrolizumab)

Pembrolizumab BIOLOGICAL

Given IV

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

Treatment (RT, temozolomide, pembrolizumab)

Radiation Therapy RADIATION

Undergo focal RT

Also known as: Cancer Radiotherapy, Irradiate, Irradiated, Irradiation, RADIATION, Radiotherapeutics, Radiotherapy, RT, Therapy, Radiation

Treatment (RT, temozolomide, pembrolizumab)

Temozolomide DRUG

Given PO

Also known as: CCRG-81045, Imidazo[5,1-d]-1,2,3,5-tetrazine-8-carboxamide, 3, 4-dihydro-3-methyl-4-oxo-, M & B 39831, M and B 39831, Methazolastone, RP-46161, SCH 52365, Temodal, Temodar

Treatment (RT, temozolomide, pembrolizumab)

Eligibility Criteria

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

You may qualify if:

• Histologically confirmed newly diagnosed glioblastoma; patients with an initial diagnosis of a lower-grade glioma are eligible if a subsequent biopsy was determined to be glioblastoma and they received no prior treatment
• No prior treatment with radiation or chemotherapy for their GBM
• No prior treatment with carmustine wafers
• Patients who have undergone recent surgery:
• Must be a minimum of 14 days from surgery
• Craniotomy or intracranial biopsy site must be adequately healed and free of drainage or cellulitis, and the underlying cranioplasty must appear intact at the time of registration
• Magnetic resonance imaging (MRI) within 72 hours of surgery OR 4 weeks from surgery
• Karnofsky performance status \>= 70%
• Stable or decreasing dose of corticosteroids within 5 days prior to treatment
• Female subject of childbearing potential should have a negative urine or serum pregnancy within 7 days 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
• Patients need not have measurable or evaluable disease
• Absolute neutrophil count (ANC) \> 1.5 x 10\^9/L
• Platelet count \> 100 x 10\^9/L; or
• Hemoglobin (Hb) \> 9.0 g/dL within 7 days prior to enrollment; note: the use of transfusion or other intervention to achieve Hb \>= 9 g/dL is acceptable
• Total bilirubin =\< 1.5 x upper limit of normal (ULN) (except in patients diagnosed with Gilbert's disease)

You may not qualify if:

• Any prior treatment for the patients GBM
• Has a known diagnosis of immunodeficiency (human immunodeficiency virus \[HIV\] 1/2 antibodies) or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment excluding steroids; attempts should be made to have patient on lowest possible dose of steroids
• History of another malignancy in the previous 3 years, with a disease-free interval of \< 3 years; 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 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 will 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 or a history of interstitial lung disease, non-infectious pneumonitis or pneumonitis
• Has an active infection requiring systemic antibiotics within 7 days of registration
• 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
• Hypertension (defined as 160/95) that is not controlled on medication
• Ongoing or active infection requiring systemic treatment
• Symptomatic congestive heart failure
• Unstable angina pectoris
• Cardiac arrhythmia
• Psychiatric illness/social situations or substance abuse disorders that would limit compliance with study requirements
• Any other illness or condition that the treating investigator feels would interfere with study compliance or would compromise the patient's safety or study endpoints
• 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

Sponsors & Collaborators

• Northwestern University: lead
• Merck Sharp & Dohme LLC: collaborator
• National Cancer Institute (NCI): collaborator

Study Sites (1)

Northwestern University

Chicago, Illinois, 60611, United States

Location

MeSH Terms

Conditions

Glioblastoma

Interventions

pembrolizumab; Radiotherapy; Radiation; Temozolomide

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

Intervention Hierarchy (Ancestors)

Therapeutics; Physical Phenomena; Dacarbazine; Triazenes; Organic Chemicals; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Karan Dixit, MD

  Northwestern University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Karan Dixit, MD

Study Record Dates

• First Submitted: August 19, 2015
• First Posted: August 21, 2015
• Study Start: September 30, 2015
• Primary Completion: May 10, 2016
• Study Completion: February 12, 2020
• Last Updated: November 18, 2023

Record last verified: 2023-11

Locations

US (1)