6 Months Adjuvant Temozolomide (TMZ) vs No Adjuvant TMZ in Newly Diagnosed MGMT Methylated Glioblastoma (GBM)

NCT04926168 | Withdrawn DMC

• 2 other identifiers: ABTCv2-2101IRB00285623
• Study Type: observational
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

The primary objective of this trial is to evaluate overall survival of patients with O\[6\]-methylguanine-DNA methyltransferase (MGMT) methylated glioblastoma treated with or without six months of adjuvant TMZ after standard radiation (6000 centigray (cGy)) plus concurrent Temozolomide (TMZ). Secondary Objectives include to prospectively assess the overall adverse event profile in the two treatment arms. To compare lymphocyte counts overtime between the two treatment arms and to prospectively compare quality of life in the two treatment arms as assessed by MD Anderson Symptom Inventory-Brain Tumor Module (MDASI-BT) and Neurological quality of Life/minimal infecting dose (NeuroQoL) (MID). The study will also compare progression-free survival between the two treatment arms.

Conditions

MGMT-Methylated Glioblastoma

Keywords

TMZ; MGMT; adjuvant TMZ; GBM, Newly Diagnosed

Outcome Measures

Primary Outcomes (1)

• Overall Survival

  Compare overall survival with patients receiving adjuvant TMZ to those having TMZ delayed

  Up to 2 years

Secondary Outcomes (5)

• Grade 3 or above adverse events

  6 months

• Change in Lymphocyte count

  Up to 1 year

• Change in Quality of life as assessed by MDASI-BT

  Up to 6 months

• Change in Quality of life as assessed by NeuroQoL/MID.

  Up to 6 months

• Progression-free survival

  Up to 2 years

Study Arms (2)

Adjuvant TMZ (Treatment group):

Adjuvant TMZ (temozolomide) will be given to patients as standard of Care (SOC) treatment is administered on an outpatient basis. Patients will be provided with medication diaries and instructed in their use. TMZ will be dispensed as SOC.

Other: Standard of Care (SOC) Adjuvant TMZ (no intervention

Delay TMZ (Observation group):

Patients in this cohort will have their TMZ in the adjuvant setting delayed and they will be observed with SOC procedures. Once the patient recurs, will be off "observation" and will be able to either have TMZ prescribed or something other.

Other: Delay of TMZ

Interventions

Delay of TMZ OTHER

Delay of TMZ to analyze the current standard of care practice of prescribing TMZ post combination (RT and TMZ).

Delay TMZ (Observation group):

Standard of Care (SOC) Adjuvant TMZ (no intervention OTHER

SOC in Adjuvant Setting no intervention

Adjuvant TMZ (Treatment group):

Eligibility Criteria

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

Study Population

patients who have completed 6weeks of TMZ + RT and have had good performance in that setting are eligible to be enrolled in this study to observe outcomes from being randomized to receive Standard of Care Adjuvant TMZ (6months TMZ 5 Days 1-5 or each cycle) or delay of adjuvant TMZ until recurrence post TMZ and RT. At recurrence patient may choose to start TMZ or some other treatment.

You may qualify if:

• Patients must be 18 years of age or older.
• Patients must have a Karnofsky Performance Status ≥ 60% (i.e. the patient must be able to care for himself/herself with occasional help from others).
• Patients must have had a pathologically confirmed recently diagnosed primary glioblastoma before they began concurrent radiation and temozolomide.
• Patients must have tumor MGMT methylation status of methylated using a Clinical Laboratory Improvement Amendments (CLIA)-approved diagnostic test. Results of routinely-used methods for MGMT methylation testing (e.g. Mutagenically separated- polymerase chain reaction (MS-PCR) or quantitative PCR) are acceptable.
• Documented mutated isocitrate dehydrogenase 1 gene (IDH1) isocitrate dehydrogenase 1 gene (IDH2)status: patients with either wild-type or(IDH) status are eligible. Patients with no documented status are also eligible and the status should be listed as unknown.
• Patients must be completing or have completed 6 weeks of standard concurrent RT/TMZ.
• Patients' post-operative treatment must have included at least 80% of standard radiation and concomitant temozolomide. Patients may not have received any other prior chemotherapy, immunotherapy or therapy with biologic agent (including immunotoxins, immunoconjugates, antisense, peptide receptor antagonists, interferons, interleukins, tumor-infiltrating lymphocytes (TIL), lymphokine activated killer cells (LAK) or gene therapy), or hormonal therapy for their brain tumor. Prior Gliadel Wafers are allowed. Glucocorticoid therapy is allowed.
• Patients must be clinically eligible for the six months of adjuvant temozolomide.
• Patients must be able to provide written informed consent.
• Patients must have baseline MRI performed within the 21 days prior to starting entering the "adjuvant" treatment or observation period.
• Patients must have the following organ and marrow functions:
• Absolute neutrophil count ≥1,500/µL Platelets ≥100,000/µL Hemoglobin ≥ 9 g/dL Total bilirubin ≤1.5 × institutional upper limit of normal (ULN), (except for patients with known Gilbert's syndrome who must have normal direct bilirubin) aspartate aminotransferase (AST) serum glutamic-oxaloacetic transaminase (SGOT)/ alanine transaminase (ALT) serum glutamic-pyruvic transaminase (SGPT) ≤ 2.5 × ULN Creatinine ≤1.5 × ULN OR Creatinine clearance ≥ 60 mL/min/1.73m2

You may not qualify if:

• Patients receiving any other standard or investigational agents or who plan to use the OPTUNE device or other therapies for the glioblastoma are ineligible.
• Patients with uncontrolled intercurrent illness including, but not limited to, ongoing or active infection or psychiatric illness/social situations that would limit compliance with study requirements, are ineligible.
• Patients must not have received prior RT, chemotherapy (except for their concurrent radiation and temozolomide for their recently diagnosed glioblastoma), immunotherapy or therapy with a biologic agent (including immunotoxins, immunoconjugates, antisense, peptide receptor antagonists, interferons, interleukins, tumor-infiltrating lymphocytes, lymphokine-activated killer cells, or gene therapy), or hormonal therapy for their brain tumor. Corticosteroid therapy is allowed.
• Patients must not have had a prior diagnosis of a lower grade glioma.
• No active treatment for other cancers in the past 3 years.

Sponsors & Collaborators

• Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins: lead

MeSH Terms

Conditions

Glioblastoma

Interventions

Standard of Care

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)

Quality Indicators, Health Care; Quality of Health Care; Health Services Administration; Health Care Quality, Access, and Evaluation

Study Officials

• Stuart Grossman, MD

  Johns Hopkins University

  STUDY CHAIR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 8, 2021
• First Posted: June 15, 2021
• Study Start: March 1, 2023
• Primary Completion: December 31, 2025
• Study Completion (Estimated): December 31, 2026
• Last Updated: August 10, 2022

Record last verified: 2022-08