ACTIVE_NOT_RECRUITING

GammaTile and Stupp in Newly Diagnosed GBM

Conditions

Glioblastoma Newly Diagnosed Stupp GammaTile External Beam Radiation Therapy Temozolomide Resection Brain Tumor EBRT Glioma

Quick Navigation

Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

In summary, standard of care postoperative chemoradiation for patients with newly diagnosed GBM does not routinely provide durable local control or prolonged overall survival. As discussed above it seems unlikely that patient outcomes will be significantly improved with radiation dose escalation given at the time of the EBRT boost. However, as most failures are local, improving LC could potentially improve the OS of patients. To do this, we propose a shift in the traditional radiation paradigm. This study will assess the feasibility and tolerability of adding GT radiation therapy as an upfront boost at the time of maximum safe resection, along with the backbone of the current standard of care approach, concomitant and adjuvant temozolomide +/- TTF, for patients with newly diagnosed GBM. GT, a novel brain brachytherapy device utilizing Cs-131 embedded in bioresorbable collagen tiles, offers a more sophisticated carrier and a shorter half-life radioisotope, Cs-131. Use of this device allows for radiation initiation at an earlier time point and a more rapid dose delivery and possibly more effective tumor control particularly for rapidly proliferating tumors such as GBM. Two prospective studies have demonstrated the safety and efficacy of re-irradiation with GT in patients with recurrent GBM. The overarching goal of this single-arm, open label phase 4 study is to determine the feasibility and tolerability of treating patients with GammaTile in combination with the Stupp Protocol and how to proceed with testing this treatment in a future, larger, randomized clinical study. The aims of the study are to demonstrate that the use of GammaTile at the time of surgery is well tolerated and does not delay the start of the Stupp protocol. Efficacy outcomes (e.g., LC, OS, PFS) will also be described.

Official Title

Pilot Study of Resection and GammaTile Followed by Concomitant External Beam Radiation Therapy (EBRT) and Temozolomide (TMZ) and Adjuvant in Newly Diagnosed Glioblastoma (GBM)

Quick Facts

Study Start:2022-08-17

Study Completion:2027-12-01

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:ACTIVE_NOT_RECRUITING

Study ID

NCT05342883

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:18 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion Criteria
1. All patients must be ≥ 18 years of age 2. Histopathological and molecular confirmation of newly diagnosed GBM using IDH mutation testing (such as immunohistochemistry for IDH1 R132H) must be performed as part of SOC. A central lab will perform cytogenetics testing. Note: In patients without prior biopsy, diagnosis will be suspected preoperatively, but must be confirmed by molecular testing (i.e., must be IDH wild type). Patients with confirmed pathology from biopsy prior to enrollment are able to participate if they meet all other study requirements. Enrolled patients not ultimately confirmed to have molecular GBM or are found to have IDH mutated tumors after resection and GT placement (if appropriate), will be followed for safety. If tested before screening, patients known to have IDH mutated tumors should not be invited to participate or consented/enrolled. 3. Adequate tissue for central submission to determine methylation promoter status. Patients with either methylated or unmethylated MGMT promoter status are included, and this status must be confirmed by central pathology review. Note: Patients with tissue that is insufficient or inadequate for analysis, fails MGMT testing, or has indeterminate MGMT promoter status will receive GT (if indicated) and will be part of the ITT/safety population but will be excluded from the PP population analyses. 4. A supratentorial tumor that in the opinion of the enrolling neurosurgeon is a) amenable to attempted gross total resection (GTR) and b) has a maximum preoperative diameter of 6 cm or less when considering all tumor planned for resection (enhancing and non-enhancing). If multifocal, must be fully resectable in one operative bed. Prior diagnostic biopsy allowed. Surgical protocol will follow current institutional standards. If intraoperative MRI is utilized, details will be captured. 5. Able to receive 5-aminolevulinic acid (5-ALA, Gleolan) or other institutionally standard immunofluorescent-guidance such as fluorescein, prior to surgery to optimize GTR of enhancing tumor. 6. Patient is appropriate candidate to receive SOC treatment for newly diagnosed GBM as usually practiced (Stupp protocol with at least 6 cycles and up to 12 cycles of TMZ). 7. Concomitant systemic or local anti-cancer medications or treatments are prohibited in this study (with the exception of TTF) before progression. 8. Anti-angiogenic therapy (e.g., bevacizumab and its biosimilars) or steroid use is allowed for symptom management (e.g., brain edema or symptomatic pseudoprogression) as per institutional standard. Note: For both agents, utilization of the lowest useful doses and shortest useful courses are encouraged. At failure, tumor therapeutic dose of anti-angiogenic therapy (e.g., bevacizumab and its biosimilars) or other therapies can be utilized for treatment at the investigators' discretion. 9. Karnofsky Performance Scale (KPS) score of ≥ 70. 10. Eastern Cooperative Oncology Group Performance Score (ECOG-PS) of 0-2. 11. Ability to understand and the willingness to sign (personally or by a legally authorized representative) the written IRB approved informed consent document prior to performance of any study-related procedures. 12. Ability to understand English or Spanish. 13. Patients must be willing and able to comply with scheduled visits, treatment plan, and laboratory tests and accessible for follow-up after treatment termination. 14. Men and women of childbearing potential must be willing to employ adequate contraception throughout the study and for men for up to 3 months after completing treatment. 15. Satisfactory hematology as evidenced by standard pre-surgery labs: 1. Hemoglobin ≥ 10 g/dl 2. Leukocytes ≥ 2,000/mm3 3. Absolute neutrophil count (ANC) ≥ 1,500/mm3 4. Platelets ≥ 100,000/mm3 5. Total bilirubin ≤ 2.0 x institutional/lab upper limit of normal (ULN) 6. Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase \[SGOT\]) ≤ 2.5 x ULN 7. Alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) ≤ 2.5 x ULN 8. Serum creatinine ≤ 1.5 x ULN OR creatinine clearance (CrCl) ≥ 50mL/min (if using the Cockcroft-Gault formula) 9. Absolute lymphocyte count between 1,000 and 4,800 per microliter of blood.	1. Known to be IDH mutated glioma by prior biopsy. 2. Patients not appropriate for concomitant or maintenance temozolomide. 3. Previous chemotherapy or radiotherapy to the head or neck region resulting in overlapping fields or prior surgery to the brain to resect other brain tumors. 4. Staged surgery planned (prior biopsy allowed). 5. Bilateral tumors, or multi-focal tumors that cannot be encompassed in one operative field. 6. Enhancing extension into brainstem or thalamus, or significant invasion into the corpus callosum that would preclude a high likelihood of GTR. 7. Prior invasive malignancy (except non-melanomatous skin cancer, cervical cancer in situ) unless disease free for a minimum of 2 years 8. Definitive clinical or radiologic evidence of cancer outside the brain (excluding nonmelanomatous skin cancer, or other types of indolent cancers) not needing active treatment within the past 2 years. Contact the Medical Monitor to review any inquiries on indolent cancers allowed. 9. Concomitant systemic or local anti-cancer medications or treatments in use or planned (with the exception of TTF before progression or on protocol TMZ). 10. Planned use of adjuvant anti-angiogenic therapy (e.g., bevacizumab and its biosimilars) specifically for tumor treatment 11. Enrollment in another investigational study or planned use of investigational therapies. Note: Experimental therapies or enrollment in a subsequent study are allowed after a patient on study has a local recurrence or distant brain failure. 12. Patients with contraindication to MRI or CT 13. History of allergic reactions attributed to compounds of similar chemical or biologic composition to temozolomide, bovine -derived collagen, 5-ALA or other institutionally standard immunofluorescent-guidance compounds, such as fluorescein. 14. Participants with severe intercurrent illness that will prohibit subsequent chemotherapy and radiotherapy including, but not limited to, unstable systemic disease including ongoing or active infection, COVID-19, uncontrolled hypertension, serous cardiac arrythmia requiring medication, acute cardiovascular disease or clinically manifested myocardial insufficiency or history of myocardial infarction during the past 6 months prior to screening, severe psychiatric illness or other illness that, in the judgment of the investigator, would make the patient inappropriate for entry into this study or interfere significantly with proper assessment of safety and adverse events of the prescribed regimens. 15. Women who are pregnant or lactating. Women of child-bearing potential must have a negative urine test or serum beta human chorionic gonadotrophin (b-HCG) documented no greater than 14 days prior to study registration unless they are surgically sterile (e.g. oophorectomy, hysterectomy, tubal ligation) or menopausal. Menopause is defined as 12 months of amenorrhea in a woman over 45 in the absence of possible causes for amenorrhea (e.g., low body fat, hormonal imbalances, etc.) 16. Any concomitant therapy (e.g., strict ketogenic diet, high dose vitamin C) that, in the investigator's opinion, would interfere with the evaluation of the safety or efficacy of any of the study treatments. 17. History of any psychiatric condition that might impair patient's ability to understand or comply with the requirements of the study or to provide consent. 18. Participants who, in the investigator's opinion, are unable to understand the protocol or to give informed consent (personally or by a legally authorized representative), have a history of poor cooperation, noncompliance with medical treatment, or difficulty in returning for follow up care.

Inclusion Criteria

Exclusion Criteria

1. All patients must be ≥ 18 years of age
2. Histopathological and molecular confirmation of newly diagnosed GBM using IDH mutation testing (such as immunohistochemistry for IDH1 R132H) must be performed as part of SOC. A central lab will perform cytogenetics testing. Note: In patients without prior biopsy, diagnosis will be suspected preoperatively, but must be confirmed by molecular testing (i.e., must be IDH wild type). Patients with confirmed pathology from biopsy prior to enrollment are able to participate if they meet all other study requirements. Enrolled patients not ultimately confirmed to have molecular GBM or are found to have IDH mutated tumors after resection and GT placement (if appropriate), will be followed for safety. If tested before screening, patients known to have IDH mutated tumors should not be invited to participate or consented/enrolled.
3. Adequate tissue for central submission to determine methylation promoter status. Patients with either methylated or unmethylated MGMT promoter status are included, and this status must be confirmed by central pathology review. Note: Patients with tissue that is insufficient or inadequate for analysis, fails MGMT testing, or has indeterminate MGMT promoter status will receive GT (if indicated) and will be part of the ITT/safety population but will be excluded from the PP population analyses.
4. A supratentorial tumor that in the opinion of the enrolling neurosurgeon is a) amenable to attempted gross total resection (GTR) and b) has a maximum preoperative diameter of 6 cm or less when considering all tumor planned for resection (enhancing and non-enhancing). If multifocal, must be fully resectable in one operative bed. Prior diagnostic biopsy allowed. Surgical protocol will follow current institutional standards. If intraoperative MRI is utilized, details will be captured.
5. Able to receive 5-aminolevulinic acid (5-ALA, Gleolan) or other institutionally standard immunofluorescent-guidance such as fluorescein, prior to surgery to optimize GTR of enhancing tumor.
6. Patient is appropriate candidate to receive SOC treatment for newly diagnosed GBM as usually practiced (Stupp protocol with at least 6 cycles and up to 12 cycles of TMZ).
7. Concomitant systemic or local anti-cancer medications or treatments are prohibited in this study (with the exception of TTF) before progression.
8. Anti-angiogenic therapy (e.g., bevacizumab and its biosimilars) or steroid use is allowed for symptom management (e.g., brain edema or symptomatic pseudoprogression) as per institutional standard. Note: For both agents, utilization of the lowest useful doses and shortest useful courses are encouraged. At failure, tumor therapeutic dose of anti-angiogenic therapy (e.g., bevacizumab and its biosimilars) or other therapies can be utilized for treatment at the investigators' discretion.
9. Karnofsky Performance Scale (KPS) score of ≥ 70.
10. Eastern Cooperative Oncology Group Performance Score (ECOG-PS) of 0-2.
11. Ability to understand and the willingness to sign (personally or by a legally authorized representative) the written IRB approved informed consent document prior to performance of any study-related procedures.
12. Ability to understand English or Spanish.
13. Patients must be willing and able to comply with scheduled visits, treatment plan, and laboratory tests and accessible for follow-up after treatment termination.
14. Men and women of childbearing potential must be willing to employ adequate contraception throughout the study and for men for up to 3 months after completing treatment.
15. Satisfactory hematology as evidenced by standard pre-surgery labs:
1. Hemoglobin ≥ 10 g/dl
2. Leukocytes ≥ 2,000/mm3
3. Absolute neutrophil count (ANC) ≥ 1,500/mm3
4. Platelets ≥ 100,000/mm3
5. Total bilirubin ≤ 2.0 x institutional/lab upper limit of normal (ULN)
6. Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase \[SGOT\]) ≤ 2.5 x ULN
7. Alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) ≤ 2.5 x ULN
8. Serum creatinine ≤ 1.5 x ULN OR creatinine clearance (CrCl) ≥ 50mL/min (if using the Cockcroft-Gault formula)
9. Absolute lymphocyte count between 1,000 and 4,800 per microliter of blood.

1. Known to be IDH mutated glioma by prior biopsy.
2. Patients not appropriate for concomitant or maintenance temozolomide.
3. Previous chemotherapy or radiotherapy to the head or neck region resulting in overlapping fields or prior surgery to the brain to resect other brain tumors.
4. Staged surgery planned (prior biopsy allowed).
5. Bilateral tumors, or multi-focal tumors that cannot be encompassed in one operative field.
6. Enhancing extension into brainstem or thalamus, or significant invasion into the corpus callosum that would preclude a high likelihood of GTR.
7. Prior invasive malignancy (except non-melanomatous skin cancer, cervical cancer in situ) unless disease free for a minimum of 2 years
8. Definitive clinical or radiologic evidence of cancer outside the brain (excluding nonmelanomatous skin cancer, or other types of indolent cancers) not needing active treatment within the past 2 years. Contact the Medical Monitor to review any inquiries on indolent cancers allowed.
9. Concomitant systemic or local anti-cancer medications or treatments in use or planned (with the exception of TTF before progression or on protocol TMZ).
10. Planned use of adjuvant anti-angiogenic therapy (e.g., bevacizumab and its biosimilars) specifically for tumor treatment
11. Enrollment in another investigational study or planned use of investigational therapies. Note: Experimental therapies or enrollment in a subsequent study are allowed after a patient on study has a local recurrence or distant brain failure.
12. Patients with contraindication to MRI or CT
13. History of allergic reactions attributed to compounds of similar chemical or biologic composition to temozolomide, bovine -derived collagen, 5-ALA or other institutionally standard immunofluorescent-guidance compounds, such as fluorescein.
14. Participants with severe intercurrent illness that will prohibit subsequent chemotherapy and radiotherapy including, but not limited to, unstable systemic disease including ongoing or active infection, COVID-19, uncontrolled hypertension, serous cardiac arrythmia requiring medication, acute cardiovascular disease or clinically manifested myocardial insufficiency or history of myocardial infarction during the past 6 months prior to screening, severe psychiatric illness or other illness that, in the judgment of the investigator, would make the patient inappropriate for entry into this study or interfere significantly with proper assessment of safety and adverse events of the prescribed regimens.
15. Women who are pregnant or lactating. Women of child-bearing potential must have a negative urine test or serum beta human chorionic gonadotrophin (b-HCG) documented no greater than 14 days prior to study registration unless they are surgically sterile (e.g. oophorectomy, hysterectomy, tubal ligation) or menopausal. Menopause is defined as 12 months of amenorrhea in a woman over 45 in the absence of possible causes for amenorrhea (e.g., low body fat, hormonal imbalances, etc.)
16. Any concomitant therapy (e.g., strict ketogenic diet, high dose vitamin C) that, in the investigator's opinion, would interfere with the evaluation of the safety or efficacy of any of the study treatments.
17. History of any psychiatric condition that might impair patient's ability to understand or comply with the requirements of the study or to provide consent.
18. Participants who, in the investigator's opinion, are unable to understand the protocol or to give informed consent (personally or by a legally authorized representative), have a history of poor cooperation, noncompliance with medical treatment, or difficulty in returning for follow up care.

Contacts and Locations

Study Locations (Sites)

HonorHeath Scottsdale Osborn Medical Center

Scottsdale, Arizona, 85251

United States

Keck Medicine of USC

Los Angeles, California, 90033

United States

UC Davis Comprehensive Cancer Center

Sacramento, California, 95817

United States

Advent Health Orlando

Orlando, Florida, 32803

United States

Florida Health Sciences Center, Inc. d/b/a Tampa General Hospital

Tampa, Florida, 33606

United States

Piedmont Healthcare

Atlanta, Georgia, 30309

United States

RUSH University

Chicago, Illinois, 60607

United States

Indiana University Office of Clinical Research

Indianapolis, Indiana, 46202

United States

University of Kansas Hospital

Kansas City, Kansas, 66016

United States

Henry Ford Health System

Detroit, Michigan, 48202

United States

University of Minnesota

Minneapolis, Minnesota, 55485

United States

St. Louis University Hospital Center

St Louis, Missouri, 63110

United States

ECU Health Medical Center - Vidant

Greenville, North Carolina, 27834

United States

Kettering Medical Center

Kettering, Ohio, 45429

United States

Brown University Health

Providence, Rhode Island, 02906

United States

UTHealth Houston | Memorial Hermann Health System

Houston, Texas, 77030

United States

Collaborators and Investigators

Sponsor: GT Medical Technologies, Inc.

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2022-08-17

Study Completion Date2027-12-01

Study Record Updates

Study Start Date2022-08-17

Study Completion Date2027-12-01

Terms related to this study

Keywords Provided by Researchers

Glioblastoma
Newly Diagnosed
Stupp
GammaTile
External Beam Radiation Therapy
Temozolomide
Resection
Brain
Tumor
EBRT
Glioma

Additional Relevant MeSH Terms

Glioblastoma