Neoadjuvant Chemoradiation for Resectable Glioblastoma

NCT04209790 | Terminated Phase 2 Results DMC FDA Drug

• 1 other identifier: 2019-0623
• Study Type: interventional
• Target: 2
• Locations: 1 country
• Sites: 2

Brief Summary

Preoperative therapy has not been well studied in resectable glioblastoma. This study attempts to prospectively assess the feasibility and efficacy of preoperative chemo radiation in improving local control, as this is the predominant mode of failure in these patients leading to poor outcomes. This Phase II study design would be used to proceed with the study treatment after meeting pre-specified events in the initial phase, with goal being to determine whether the new treatment paradigm is sufficiently promising to warrant a major controlled clinical evaluation against the standard therapy.

Conditions

Glioblastoma; Surgery; High Grade Glioma

Keywords

Glioblastoma

Outcome Measures

Primary Outcomes (2)

• No Study Related Undue Toxicity or Progression

  Number of participants with no study related undue toxicity or progression within the limits of stage one patients. Toxicity is defined as: progression precluding surgery, unanticipated neurological decompensation, non-completion of neoadjuvant therapy (other than protocol defined dose adjustments or discontinuation), treatment related delay of \>6 weeks to surgery, and/or major unforeseen surgical complication requiring repeat surgical intervention including other than non-life-threatening infection like meningitis/encephalitis or septicemia.

  7 months for each patient from registration

• Progression Free Survival

  Number of participants with Progression Free Survival/clinical progression with new or worsening neurological symptoms related to the tumor and not due to non-tumor or study related symptoms.

  7 months after completion of therapy

Study Arms (1)

Neoadjuvant chemoradiation and surgical resection

OTHER

The experimental part of the study would be this selection of resectable patients and sequencing neoadjuvant chemoradiation prior to surgery.

Radiation: Neoadjuvant chemoradiation; Drug: Drug Therapy with Temozolomide (benzolamide) (Standard of Care); Procedure: Surgery post Radiation and Temozolomide (benzolamide)

Interventions

Neoadjuvant chemoradiation RADIATION

Intensity modulation radiation therapy (IMRT) with a simultaneous integrated boost with Fixed-gantry IMRT, helical tomotherapy, or Vesicular Modulated Arc Therapy (VMAT) can be used. All photon treatments shall be delivered with megavoltage machines of a minimum energy of 6 Megavolt (MV) photons. Selection of the appropriate photon energy(ies) should be based on optimizing the radiation dose distribution within the target volume and minimizing dose to non-target normal tissue.

Also known as: Standard adjuvant therapy

Neoadjuvant chemoradiation and surgical resection

Drug Therapy with Temozolomide (benzolamide) (Standard of Care) DRUG

During Concomitant Radiation Therapy on the same day as the first fraction of radiotherapy. Temozolomide will be administered continuously from day 1 of radiotherapy to the last day of radiation at a daily oral dose of 75 mg/m2 for a maximum of 49 days. The drug will be administered orally daily during radiotherapy, as best tolerated by the patient. During weekends without radiotherapy (Saturday and Sunday), the drug will be taken in the morning. The dose will be determined using actual body surface area (BSA) as calculated in square meters at the beginning of the concomitant treatment. The BSA will be calculated from the height obtained at the pretreatment visit. Capsules of temozolomide are available in 5, 20, 100, 140, 180, and 250 mg. The daily dose will be rounded to the nearest 5 mg.

Also known as: Neoadjuvant therapy

Neoadjuvant chemoradiation and surgical resection

Surgery post Radiation and Temozolomide (benzolamide) PROCEDURE

Surgical resection of GBM will be done after radiation and Temozolomide treatment.

Neoadjuvant chemoradiation and surgical resection

Eligibility Criteria

• Age: 18 Years - 89 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Newly diagnosed GBM with histopathological confirmation.
• Surgically suitable for subtotal or gross total resection as determined by central review.
• Karnofsky Performance Status (KPS)\>70
• No contraindication for chemoradiation.
• Complete blood count (CBC)/differential obtained within 28 days prior to registration, with adequate bone marrow function defined as follows:
• Absolute neutrophil count (ANC) ≥ 1,500 cells/mm3;
• Platelets ≥ 100,000 cells/mm3;
• Hemoglobin ≥ 8.0 g/dl (Note: the use of transfusion or other intervention to achieve Hgb ≥8.0 g/dl is acceptable)
• Adequate hepatic function within 28 days prior to registration, as defined below:
• Alanine Aminotransferase (ALT) and Aspartate transaminase (AST) ≤ 3 x ULN
• Bilirubin ≤ 1.5 upper limit of normal (ULN)
• Negative serum pregnancy test obtained for females of child-bearing potential within 28 days prior to step 2 registration.
• Ability to get multiplanar contrast enhanced Magnetic Resonance Imaging (MRI)

You may not qualify if:

• Recurrent, unresectable or multifocal malignant gliomas.
• Any site of distant disease (for example, drop metastases from the GBM tumor site)
• Prior radiation or chemotherapy or radiosensitizers for cancers of the brain and head and neck region; note that prior chemotherapy for a different cancer is allowable (except temozolomide).
• Patents treated on any other therapeutic clinical protocols within 30 days prior to registration.
• Inability to undergo MRI (e.g., due to safety reasons, such as presence of a pacemaker, or severe claustrophobia).
• Severe, active co-morbidity, defined as follows:
• Transmural myocardial infarction within the last 6 months prior to registration
• History of recent myocardial infarction 1month prior
• New York Heart Association grade II or greater congestive heart failure requiring hospitalization within 3 months prior to 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
• Acquired immune deficiency syndrome (AIDS) based upon current Center for Disease Control (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 immuno-compromised condition.

Sponsors & Collaborators

• Geisinger Clinic: lead

Study Sites (2)

Geisinger Medical Center

Danville, Pennsylvania, 17822, United States

Location

Geisinger Wyoming Valley Medical Center

Wilkes-Barre, Pennsylvania, 18711, United States

Location

Related Publications (5)

• Milano MT, Okunieff P, Donatello RS, Mohile NA, Sul J, Walter KA, Korones DN. Patterns and timing of recurrence after temozolomide-based chemoradiation for glioblastoma. Int J Radiat Oncol Biol Phys. 2010 Nov 15;78(4):1147-55. doi: 10.1016/j.ijrobp.2009.09.018. Epub 2010 Mar 6.

  PMID: 20207495 BACKGROUND

• Stupp R, Mason WP, van den Bent MJ, Weller M, Fisher B, Taphoorn MJ, Belanger K, Brandes AA, Marosi C, Bogdahn U, Curschmann J, Janzer RC, Ludwin SK, Gorlia T, Allgeier A, Lacombe D, Cairncross JG, Eisenhauer E, Mirimanoff RO; European Organisation for Research and Treatment of Cancer Brain Tumor and Radiotherapy Groups; National Cancer Institute of Canada Clinical Trials Group. Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med. 2005 Mar 10;352(10):987-96. doi: 10.1056/NEJMoa043330.

  PMID: 15758009 BACKGROUND

• Yarbro JW. Future potential of adjuvant and neoadjuvant therapy. Semin Oncol. 1991 Dec;18(6):613-9. No abstract available.

  PMID: 1775978 BACKGROUND

• Filatova A, Acker T, Garvalov BK. The cancer stem cell niche(s): the crosstalk between glioma stem cells and their microenvironment. Biochim Biophys Acta. 2013 Feb;1830(2):2496-508. doi: 10.1016/j.bbagen.2012.10.008. Epub 2012 Oct 16.

  PMID: 23079585 BACKGROUND

• Rycaj K, Tang DG. Cancer stem cells and radioresistance. Int J Radiat Biol. 2014 Aug;90(8):615-21. doi: 10.3109/09553002.2014.892227. Epub 2014 Mar 7.

  PMID: 24527669 BACKGROUND

MeSH Terms

Conditions

Glioblastoma; Glioma

Interventions

Neoadjuvant Therapy; Drug Therapy; Temozolomide; Benzolamide; Standard of Care

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Combined Modality Therapy; Therapeutics; Dacarbazine; Triazenes; Organic Chemicals; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Sulfonamides; Amides; Sulfones; Sulfur Compounds; Thiadiazoles; Thiazoles; Quality Indicators, Health Care; Quality of Health Care; Health Services Administration; Health Care Quality, Access, and Evaluation

Results Point of Contact

• Title: Regulatory Project Manager
• Organization: Geisinger

khassanzadeh@geisinger.edu

570-214-2462

Study Officials

• Michel Lacroix, M.D.

  Geisinger Clinic

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes
• Restrictive Agreement: No

Study Design

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

Model Details: After standard treatment of Glioblastoma multiforme (GBM) with resection and adjuvant therapy, local failure the dominant pattern of failure. Neo adjuvant therapy consistently provides the potential for improved local control and removal of residual stem cell niches. The hypothesis is that earlier institution of neo adjuvant chemo radiation therapy in GBM would improve local control and potentially overall survival. Involved field radiation is often employed to treat unresectable or sub totally resected GBM. Radiating native GBM is not uncommon as many tumors are not safely resectable due to its location in eloquent brain. Planned neoadjuvant chemo radiation prior to immediate surgical resection in glioblastoma is a novel approach in resectable tumors.

Study Record Dates

• First Submitted: December 17, 2019
• First Posted: December 24, 2019
• Study Start: April 1, 2020
• Primary Completion: September 14, 2022
• Study Completion: September 14, 2022
• Last Updated: November 10, 2025
• Results First Posted: November 10, 2025

Record last verified: 2025-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)