Don't get left behind! The modernized ClinicalTrials.gov is coming. Check it out now.
Say goodbye to ClinicalTrials.gov!
The new site is coming soon - go to the modernized ClinicalTrials.gov
Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Testing the Addition of the Chemotherapy Drug Lomustine (Gleostine®) to the Usual Treatment (Temozolomide and Radiation Therapy) for Newly Diagnosed MGMT Methylated Glioblastoma

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT05095376
Recruitment Status : Recruiting
First Posted : October 27, 2021
Last Update Posted : March 28, 2023
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
NRG Oncology

Study Description
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information
Brief Summary:
This phase III trial compares the effect of adding lomustine to temozolomide and radiation therapy versus temozolomide and radiation therapy alone in shrinking or stabilizing newly diagnosed MGMT methylated glioblastoma. Chemotherapy drugs, such as lomustine and temozolomide, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Radiation therapy uses high energy photons to kill tumor cells and shrink tumors. Adding lomustine to usual treatment of temozolomide and radiation therapy may help shrink and stabilize glioblastoma.

Condition or disease Intervention/treatment Phase
Glioblastoma Gliosarcoma Drug: Lomustine Radiation: Photon Beam Radiation Therapy Other: Quality-of-Life Assessment Other: Questionnaire Administration Drug: Temozolomide Phase 3

Detailed Description:

PRIMARY OBJECTIVE:

I. To determine if the regimen with the two alkylating agents temozolomide and lomustine with radiotherapy (RT) significantly prolongs overall survival (OS) versus (vs.) standard chemoradiotherapy with temozolomide in patients with newly diagnosed glioblastoma (GBM) with MGMT promoter methylation.

SECONDARY OBJECTIVES:

I. To determine if the regimen with the two alkylating agents temozolomide and lomustine with radiotherapy (RT) significantly prolongs progression-free survival (PFS) vs. standard chemoradiotherapy with temozolomide in patients with newly diagnosed GBM with MGMT promoter methylation.

II. To compare the two different chemotherapy regimens on patient-reported outcomes (PROs), as measured by the MD Anderson Symptom Inventory - Brain Tumor (MDASI-BT) in patients with newly diagnosed GBM with MGMT promoter methylation.

III. To determine if the regimen with the two alkylating agents temozolomide and lomustine with radiotherapy (RT) is associated with inferior short-term change in patient reported outcomes (PROs) as measured by MDASI-BT vs. standard chemoradiotherapy with temozolomide in patients with newly diagnosed GBM with MGMT promoter methylation.

IV. To assess toxicity in the two different chemotherapy regimens.

EXPLORATORY OBJECTIVES:

I. To assess the association between absolute lymphocyte counts and outcomes. II. To assess the association between CD4+ lymphocyte counts and outcomes. III. To compare the two different chemotherapy regimens in terms of long-term PROs as measured by MDASI-BT at years 1 and 2.

OUTLINE: Patients are randomized to 1 of 2 arms.

ARM I: Patients undergo radiation therapy 5 days per week and receive temozolomide orally (PO) once daily (QD) for 6 weeks in the absence of disease progression or unacceptable toxicity. Patients then receive temozolomide PO QD on days 1-5. Treatment repeats every 28 days for 6 cycles in the absence of disease progression or unacceptable toxicity.

ARM II: Patients undergo radiation therapy 5 days per week for 6 weeks in the absence of disease progression or unacceptable toxicity. Patients also receive lomustine PO on day 1 and temozolomide PO QD on days 2-6. Treatment repeats every 42 days for 6 cycles in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 3 months for year 1, every 4 months for year 2, and then every 6 months thereafter.

Study Design
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 306 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase III Trial of Gleostine® (Lomustine)-Temozolomide Combination Therapy Versus Standard Temozolomide in Patients With Methylated MGMT Promoter Glioblastoma
Actual Study Start Date : November 29, 2021
Estimated Primary Completion Date : August 8, 2026
Estimated Study Completion Date : August 8, 2031

Resource links provided by the National Library of Medicine


Arms and Interventions
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Arm Intervention/treatment
Active Comparator: Arm I (radiation therapy, temozolomide)
Patients undergo radiation therapy 5 days per week and receive temozolomide PO QD for 6 weeks in the absence of disease progression or unacceptable toxicity. Patients then receive temozolomide PO QD on days 1-5. Treatment repeats every 28 days for 6 cycles in the absence of disease progression or unacceptable toxicity.
 Radiation: Photon Beam Radiation Therapy
Undergo radiation therapy
Other Names:
  • Photon EBRT
  • Photon External Beam Radiotherapy
  • Radiation, Photon Beam

Other: Quality-of-Life Assessment
Ancillary studies
Other Name: Quality of Life Assessment

Other: Questionnaire Administration
Ancillary studies

Drug: Temozolomide
Given PO
Other Names:
  • 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
  • Temcad
  • Temodal
  • Temodar
  • Temomedac
  • TMZ
Experimental: ARM II (radiation therapy, temozolomide, lomustine)
Patients undergo radiation therapy 5 days per week for 6 weeks in the absence of disease progression or unacceptable toxicity. Patients also receive lomustine PO on day 1 and temozolomide PO QD on days 2-6. Treatment repeats every 42 days for 6 cycles in the absence of disease progression or unacceptable toxicity.
 Drug: Lomustine
Given PO
Other Names:
  • 1-(2-Chloroethyl)-3-cyclohexyl-1-nitrosourea
  • 1-Nitrosourea, 1-(2-chloroethyl)-3-cyclohexyl-
  • Belustin
  • Belustine
  • CCNU
  • Cecenu
  • CeeNU
  • Chloroethylcyclohexylnitrosourea
  • Citostal
  • Gleostine
  • Lomeblastin
  • Lomustinum
  • Lucostin
  • Lucostine
  • N-(2-Chloroethyl)-N'-cyclohexyl-N-nitrosourea
  • Prava
  • RB-1509
  • WR-139017

Radiation: Photon Beam Radiation Therapy
Undergo radiation therapy
Other Names:
  • Photon EBRT
  • Photon External Beam Radiotherapy
  • Radiation, Photon Beam

Other: Quality-of-Life Assessment
Ancillary studies
Other Name: Quality of Life Assessment

Other: Questionnaire Administration
Ancillary studies

Drug: Temozolomide
Given PO
Other Names:
  • 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
  • Temcad
  • Temodal
  • Temodar
  • Temomedac
  • TMZ


Outcome Measures
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Primary Outcome Measures :
  1. Overall Survival [ Time Frame: From randomization to death due to any cause, assessed up to 4 years ]
    The Kaplan-Meier method will be used to estimate survival distribution for each treatment arm.


Secondary Outcome Measures :
  1. Progression Free Survival (PFS) [ Time Frame: From randomization to disease progression or death due to any cause, whichever occurs first, assessed up to 4 years ]
    Analysis will consist of estimation of the PFS distribution of each treatment arm via the Kaplan-Meier method and a stratified log-rank test. Additional analyses may consist of estimating the hazard ratio (HR) via the Cox proportional hazards model, accounting for other prognostic covariates (and evaluating whether the proportional hazards assumption holds or whether any treatment effect is notably time-varying), and evaluating for potential treatment by prognostic covariate interactions.

  2. Incidence of Adverse Events [ Time Frame: Up to 4 years ]
    Adverse events (AEs) will be graded according to Common Terminology Criteria for Adverse Events version 5.0. Comprehensive summaries of all AEs by treatment arm will be generated and examined.

  3. Patient reported outcomes for Brain Tumors [ Time Frame: Up to 4 years ]
    Measured by the MD Anderson Symptom Inventory - Brain Tumor (MDASI-BT) in patients with newly diagnosed glioblastoma with MGMT promoter methylation.


Other Outcome Measures:
  1. Absolute lymphocyte counts [ Time Frame: Up to 4 years ]
    Will assess the association between absolute lymphocyte counts and outcomes.


Eligibility Criteria
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years to 70 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • STEP 1 REGISTRATION: No known IDH mutation. (If tested before step 1 registration, patients known to have IDH mutation in the tumor on local or other testing are ineligible and should not be registered)
  • STEP 1 REGISTRATION: Availability of formalin-fixed paraffin-embedded (FFPE) tumor tissue block and hematoxylin and eosin (H&E) stained slide to be sent for central pathology review for confirmation of histology and MGMT promoter methylation status. Note that tissue for central pathology review and central MGMT assessment must be received by the NYU Center for Biospecimen Research and Development (CBRD) on or before postoperative calendar day 23. If tissue cannot be received by postoperative calendar day 23, then patients may NOT enroll on this trial as central pathology review will not be complete in time for the patient to start treatment no later than 6 weeks following surgery. Results of central pathology review and central MGMT analysis will generally be conveyed to NRG Oncology within 10 business days of receipt of tissue. Note: In the event of an additional tumor resection(s), tissue must be received within 23 days of the most recent resection and the latest resection must have been performed within 30 days after the initial resection. Surgical resection is required; stereotactic biopsy alone is not allowed because it will not provide sufficient tissue for MGMT analysis

  • STEP 1 REGISTRATION: Contrast-enhanced brain MRI within 4 days after surgery

    • Magnetic resonance imaging (MRI) with Axial T2 weighted FLAIR{preferred} or T2 TSE/FSE and 3D contrast-enhanced T1 sequences are required.
    • 3-dimensional (3D) pre contrast-enhanced T1 sequences are strongly suggested
  • STEP 1 REGISTRATION: Willing to use highly effective method of contraception for participants of childbearing potential (participants who may become pregnant or who may impregnate a partner) during therapy and for 6 months after completing treatment; this inclusion is necessary because the treatment in this study may be significantly teratogenic
  • STEP 1 REGISTRATION: The patient or a legally authorized representative must provide study-specific informed consent prior to study entry and, for patients treated in the United States (U.S.), authorization permitting release of personal health information
  • STEP 2 REGISTRATION: Histopathologically proven diagnosis of glioblastoma (or gliosarcoma as a subtype of glioblastoma) confirmed by central pathology review
  • STEP 2 REGISTRATION: MGMT promoter with methylation confirmed by central pathology review (See Section 10 for details). Note: Patients with tissue that is insufficient or inadequate for analysis, fails MGMT testing, or has indeterminate or unmethylated MGMT promoter are excluded. Patients with unmethylated MGMT may be considered for enrollment on NRG-BN007
  • STEP 2 REGISTRATION: IDH mutation testing by at least one method (such as immunohistochemistry for IDH1 R132H) must be performed as part of standard of care and no mutation must be found (i.e IDH wildtype). (If a mutation is identified then the patient will be ineligible and must be registered as ineligible at Step 2.)
  • STEP 2 REGISTRATION: History/physical examination within 28 days prior to Step 2 registration
  • STEP 2 REGISTRATION: Karnofsky performance status (KPS) >= 70 within 28 days prior to Step 2 registration
  • STEP 2 REGISTRATION: Neurologic function assessment within 28 days prior to Step 2 registration
  • STEP 2 REGISTRATION: Age 18-70 years
  • STEP 2 REGISTRATION: Hemoglobin >= 10 g/dl (Note: the use of transfusion or other intervention to achieve hemoglobin (Hgb) >= 10.0 g/dl is acceptable)
  • STEP 2 REGISTRATION: Leukocytes >= 2,000/mm^3
  • STEP 2 REGISTRATION: Absolute neutrophil count >= 1,500/mm^3
  • STEP 2 REGISTRATION: Platelets >= 100,000/mm^3
  • STEP 2 REGISTRATION: Total bilirubin =< 1.5 x institutional/lab upper limit of normal (ULN)
  • STEP 2 REGISTRATION: Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT]) =< 2.5 x ULN
  • STEP 2 REGISTRATION: Alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 x ULN
  • STEP 2 REGISTRATION: Serum creatinine =< 1.5 x ULN OR creatinine clearance (CrCl) >= 50 mL/min (if using the Cockcroft-Gault formula

  • STEP 2 REGISTRATION: For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated

    • Note: Known positive test for hepatitis B virus surface antigen (HBV sAg) indicating acute or chronic infection would make the patient ineligible unless the viral load becomes undetectable on suppressive therapy. Patients who are immune to hepatitis B (anti-hepatitis B surface antibody positive) are eligible (e.g. patients immunized against hepatitis B)

  • STEP 2 REGISTRATION: For patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load

    • Note: Known positive test for hepatitis C virus ribonucleic acid (HCV ribonucleic acid [RNA]) indicating acute or chronic infection would make the patient ineligible unless the viral load becomes undetectable on suppressive therapy
  • STEP 2 REGISTRATION: Known human immunodeficiency virus (HIV) infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months prior to step 2 registration are eligible for this trial. Testing is not required for entry into protocol

  • STEP 2 REGISTRATION: Negative serum or urine pregnancy test (in persons of childbearing potential) within 7 days prior to Step 2 registration

    • Childbearing potential is defined as any person who has experienced menarche and who has not undergone surgical sterilization (hysterectomy or bilateral oophorectomy) or who is not postmenopausal

Exclusion Criteria:

  • STEP 2 REGISTRATION: Prior therapy for tumor except for resection. For example, prior chemotherapy, immunotherapy, or targeted therapy for GBM or lower grade glioma is disallowed (including but not limited to temozolomide, lomustine, bevacizumab, any viral therapy, ipilimumab or other CTLA-4 antibody, PD-1 antibody, CD-137 agonist, CD40 antibody, PDL-1 or 2 antibody, vaccine therapy, polio or similar viral injection as treatment for the tumor, and/or any other antibody or drug specifically targeting T-cell co-stimulation or immune checkpoint pathways) as is prior Laser interstitial thermal therapy (LITT), Gliadel wafer, radiotherapy, radiosurgery, vaccine or other immunotherapy, brachytherapy, or convection enhanced delivery

    • Note: 5-aminolevulinic acid (ALA)-mediated fluorescent guided resection (FGR) photodynamic therapy (PDT) or fluorescein administered prior to/during surgery to aid resection is not exclusionary and is not considered a chemotherapy or intracerebral agent
  • STEP 2 REGISTRATION: Current or planned treatment with any other investigational agents for the study cancer
  • STEP 2 REGISTRATION: Definitive clinical or radiologic evidence of metastatic disease outside the brain
  • STEP 2 REGISTRATION: Prior invasive malignancy (except non-melanomatous skin cancer, cervical cancer in situ and melanoma in situ) unless disease free for a minimum of 2 years
  • STEP 2 REGISTRATION: Prior radiotherapy to the head or neck that would result in overlap of radiation therapy fields
  • STEP 2 REGISTRATION: Pregnancy and individuals unwilling to discontinue nursing due to the potential teratogenic effects and potential risk for adverse events in nursing infants
  • STEP 2 REGISTRATION: History of allergic reactions attributed to compounds of similar chemical or biologic composition to temozolomide or lomustine
  • STEP 2 REGISTRATION: History of pulmonary fibrosis

  • STEP 2 REGISTRATION: Uncontrolled intercurrent illness including, but not limited to:

    • Ongoing or active infection requiring IV antibiotics, IV antiviral, or IV antifungal treatment
    • Symptomatic congestive heart failure, defined as New York Heart Association Functional Classification III/IV (Note: Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification)
    • Unstable angina pectoris within 6 months prior to Step 2 registration
    • Uncontrolled cardiac arrhythmia
    • Psychiatric illness/social situations that would limit compliance with study requirements
Contacts and Locations
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05095376


Locations
Show Show 225 study locations
Sponsors and Collaborators
NRG Oncology
National Cancer Institute (NCI)
Investigators
Layout table for investigator information
Principal Investigator: Fabio M Iwamoto NRG Oncology
More Information
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information
Layout table for additonal information
Responsible Party: NRG Oncology
ClinicalTrials.gov Identifier: NCT05095376    
Other Study ID Numbers: NRG-BN011
NCI-2021-10331 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
NRG-BN011 ( Other Identifier: NRG Oncology )
NRG-BN011 ( Other Identifier: CTEP )
U10CA180868 ( U.S. NIH Grant/Contract )
First Posted: October 27, 2021    Key Record Dates
Last Update Posted: March 28, 2023
Last Verified: March 2023

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Additional relevant MeSH terms:
Layout table for MeSH terms
Glioblastoma
Gliosarcoma
Astrocytoma
Glioma
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
 Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Temozolomide
Lomustine
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents