Chemotherapy and Radiation Therapy for the Treatment of IDH Wildtype Gliomas or Non-histological (Molecular) Glioblastomas

Study Purpose

This phase II trial studies how well temozolomide and radiation therapy work in treating patients with IDH wildtype historically lower grade gliomas or non-histological molecular glioblastomas. Radiation therapy uses high-energy x-rays to kill tumor cells and shrink tumors. Giving chemotherapy with radiation therapy may kill more tumor cells. Drugs used in chemotherapy, such as 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. The goal of this clinical research study is to compare receiving new radiation therapy doses and volumes to the prior standard treatment for patients with historically grade II or grade III IDH wild-type gliomas, which may now be referred to as IDH wildtype molecular glioblastomas at some institutions. Receiving temozolomide in combination with radiation therapy may also help to control the disease.

Recruitment Criteria

Accepts Healthy Volunteers

Healthy volunteers are participants who do not have a disease or condition, or related conditions or symptoms

No
Study Type

An interventional clinical study is where participants are assigned to receive one or more interventions (or no intervention) so that researchers can evaluate the effects of the interventions on biomedical or health-related outcomes.


An observational clinical study is where participants identified as belonging to study groups are assessed for biomedical or health outcomes.


Searching Both is inclusive of interventional and observational studies.

Interventional
Eligible Ages 18 Years and Over
Gender All
More Inclusion & Exclusion Criteria

Inclusion Criteria:

  • - Historical grade II and III gliomas IDH wildtype gliomas by including; diffuse astrocytoma, anaplastic astrocytoma, oligodendroglioma, anaplastic oligodendroglioma, oligoastrocytoma, anaplastic oligoastrocytoma.
  • - IDH wildtype gliomas (molecularly defined high grade glioma or molecularly defined glioblastoma [GBM]) - History & physical exam, and Karnofsky performance status (KFS) of >= 70 within 30 days prior to enrollment.
  • - Post-operative magnetic resonance imaging (MRI) with contrast is mandatory and necessary for radiation therapy (RT) planning.
  • - Thin-slice (< 1.5 mm) three-dimensional (3D) T1 pre and post contrast and axial T2/fluid-attenuated inversion recovery (FLAIR) sequences for planning purposes are highly encouraged to obtain.
  • - Absolute neutrophil count (ANC) >= 1,500 cells/mm^3 (within 60 days prior to registration) - Platelets >= 100,000 cells/mm^3 (within 60 days prior to registration) - Hemoglobin >= 10.0 g/dl (within 60 days prior to registration) (Note: The use of transfusion or other intervention to achieve hemoglobin [Hgb] >= 10.0 g/dl is acceptable) - Bilirubin =< 1.5 upper limit of normal (ULN) (within 60 days prior to registration) - Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =< 3 x ULN (within 60 days prior to registration) - Blood urea nitrogen (BUN) < 30 mg/dl (within 60 days prior to registration) - Serum creatinine < 1.5 mg/dl (within 60 days prior to registration)

    Exclusion Criteria:

    - Definitive clinical or radiologic evidence of metastatic disease; if applicable.
  • - Prior invasive malignancy (except non-melanomatous skin cancer) unless disease free for a minimum of 3 years.
(For example, carcinoma in situ of the breast, oral cavity or cervix are permissible)
  • - Prior cranial radiotherapy or radiotherapy to the head and neck where potential field overlaps would exist.
  • - Prior chemotherapy or radiotherapy for any brain tumor.
  • - Histologic diagnosis of gliosarcoma World Health Organization (WHO grade IV) or pilocytic astrocytoma (WHO grade I) - Multicentric glioblastoma.
  • - Leptomeningeal disease.
  • - Inability to undergo MRI with and without contrast.
  • - Severe, active co-morbidity defined as follows: - Unstable angina or congestive heart failure requiring hospitalization within 6 months prior to enrollment.
  • - Transmural myocardial infarction within the last 6 months prior to registration.
Evidence of recent myocardial infarction or ischemia by the findings of S-T elevations of >= 2 mm using the analysis of an electrocardiogram (EKG) performed within 28 days prior to registration. (Note: EKG to be performed only if clinical suspicion of cardiac issue) • New York Heart Association grade II or greater congestive heart failure requiring hospitalization within 12 months prior to registration.
  • - Serious and inadequately controlled arrhythmia at step 2 registration.
  • - Serious or non-healing wound, ulcer or bone fracture or history of abdominal fistula, intra-abdominal abscess requiring major surgical procedure, open biopsy or significant traumatic injury within 28 days prior to registration, with the exception of the craniotomy for surgical resection.
  • - Acute bacterial or fungal infection requiring intravenous antibiotics at the time of registration.
  • - Hepatic insufficiency resulting in clinical jaundice and/or coagulation defects; note, however, that laboratory tests for coagulation parameters are not required for entry into this protocol.
  • - Chronic obstructive pulmonary disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy at the time of registration.
  • - Human immunodeficiency virus (HIV) positive with CD4 count < 200 cells/microliter.
Acquired immune deficiency syndrome (AIDS) based upon current Centers for Disease Control and Prevention (CDC) definition; note, however, that HIV testing is not required for entry into this protocol. The need to exclude patients with AIDS from this protocol is because the treatments involved in this protocol may be significantly immunosuppressive with potentially fatal outcomes in patients already immunosuppressed.
  • - Any other severe immunocompromised condition.
  • - Active connective tissue disorders, such as lupus or scleroderma that in the opinion of the treating physician may put the patient at high risk for radiation toxicity.
- End-stage renal disease (i.e., on dialysis or dialysis has been recommended) - Any other major medical illnesses or psychiatric treatments that in the investigator's opinion will prevent administration or completion of protocol therapy

Trial Details

Trial ID:

This trial id was obtained from ClinicalTrials.gov, a service of the U.S. National Institutes of Health, providing information on publicly and privately supported clinical studies of human participants with locations in all 50 States and in 196 countries.

NCT04623931
Phase

Phase 1: Studies that emphasize safety and how the drug is metabolized and excreted in humans.

Phase 2: Studies that gather preliminary data on effectiveness (whether the drug works in people who have a certain disease or condition) and additional safety data.

Phase 3: Studies that gather more information about safety and effectiveness by studying different populations and different dosages and by using the drug in combination with other drugs.

Phase 4: Studies occurring after FDA has approved a drug for marketing, efficacy, or optimal use.

Phase 2
Lead Sponsor

The sponsor is the organization or person who oversees the clinical study and is responsible for analyzing the study data.

M.D. Anderson Cancer Center
Principal Investigator

The person who is responsible for the scientific and technical direction of the entire clinical study.

Debra N Yeboa
Principal Investigator Affiliation M.D. Anderson Cancer Center
Agency Class

Category of organization(s) involved as sponsor (and collaborator) supporting the trial.

Other
Overall Status Recruiting
Countries United States
Conditions

The disease, disorder, syndrome, illness, or injury that is being studied.

Anaplastic Astrocytoma, IDH-Wildtype, Anaplastic Oligoastrocytoma, Anaplastic Oligodendroglioma, Diffuse Astrocytoma, IDH-Wildtype, Glioblastoma, Oligoastrocytoma, Oligodendroglioma, WHO Grade II Glioma, WHO Grade III Glioma
Study Website: View Trial Website
Additional Details

PRIMARY OBJECTIVE:

  • I. To determine the progression free survival (PFS) based on Response Assessment in Neuro-Oncology (RANO) imaging criteria from start of treatment with concurrent chemoradiation (CRT) and adjuvant temozolomide (TMZ).
SECONDARY OBJECTIVE:
  • I. To determine the 3-year overall survival (OS) of isocitrate dehydrogenase (IDH) wild-type grade II and grade III gliomas with dose escalation radiation with concurrent chemoradiation therapy.
EXPLORATORY OBJECTIVES:
  • I. To assess local control patterns (site of 1st progression).
  • II. To evaluate neuro-cognitive function by the Neurocognitive Clinical Trial Battery (CTB).
  • III. To evaluate the treatment related symptoms, overall symptom impact, and disease related factor groupings utilizing the M.
D. Anderson Symptom Inventory Brain Tumor (MDASI-BT).
  • IV. To assess the quality of life.
OUTLINE: Patients receive temozolomide orally (PO) daily and radiation therapy over 5 days a week (weekdays only) for 6 weeks. Beginning 28 days after the last dose of radiation therapy, patients receive temozolomide PO for 12 months in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up at 1, 3, 5, 7, 9, 12, 15, 18, 21, 24, 28, 32, and 36 months.

Arms & Interventions

Arms

Experimental: Treatment (temozolomide, radiation therapy)

Patients receive temozolomide PO daily and radiation therapy over 5 days a week (weekdays only) for 6 weeks. Beginning 28 days after the last dose of radiation therapy, patients receive temozolomide PO for 12 months in the absence of disease progression or unacceptable toxicity.

Interventions

Other: - Quality-of-Life Assessment

Ancillary studies

Other: - Questionnaire Administration

Ancillary studies

Radiation: - Radiation Therapy

Undergo radiation therapy

Drug: - Temozolomide

Given PO

Contact a Trial Team

If you are interested in learning more about this trial, find the trial site nearest to your location and contact the site coordinator via email or phone. We also strongly recommend that you consult with your healthcare provider about the trials that may interest you and refer to our terms of service below.

M D Anderson Cancer Center, Houston, Texas

Status

Recruiting

Address

M D Anderson Cancer Center

Houston, Texas, 77030

Site Contact

Debra N. Yeboa

[email protected]

713-563-2300

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