RECRUITING

OPTIMUS PRIME: Safety and Feasibility of OPTune GIO® Integrated With MRI-gUided Laser Ablation Surgery and Pembrolizumab for Recurrent GlIoblastoMa, A randomizEd Trial

Conditions

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 this study we are evaluating the safety and feasibility of the triple combination (TTFields, MLA, pembrolizumab) in adult patients diagnosed with recurrent or progressive glioblastoma (GBM) WHO Grade IV, IDH wild type or recurrent or progressive astrocytoma WHO grade IV.

Official Title

OPTIMUS PRIME: Safety and Feasibility of OPTune GIO® Integrated With MRI-gUided Laser Ablation Surgery and Pembrolizumab for Recurrent GlIoblastoMa, A randomizEd Trial

Quick Facts

Study Start:2024-11-12

Study Completion:2029-10

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT06558214

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 to 90 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion Criteria
1. Patient must be at least 18 years of age. 2. Diagnosis of recurrent or progressive glioblastoma, WHO Grade IV, IDH wild-Type or astrocytoma WHO grade IV. 3. Unequivocal evidence of tumor progression by brain MRI scan per RANO criteria. Patients who experience a second disease progression are eligible provided that they have not been previously treated with anti-angiogenic agents including bevacizumab (at the exception of bevacizumab radiation necrotic protocol) 4. A diagnostic contrast-enhanced MRI of the brain must be performed preoperatively, within 28 days prior to study enrollment. 5. There must be an interval of at least 12 weeks from the completion of radiation therapy to study registration unless there is unequivocal evidence for tumor recurrence per RANO criteria. When the interval is less than 12 weeks but more than 4 weeks from the completion of radiotherapy, the use of perfusion imaging and/or PET scan is allowed to differentiate between unequivocal evidence of tumor recurrence and pseudoprogression. 6. Karnofsky performance status (KPS) ≥60%. 7. Candidate for MLA based on the size, location, and shape of the recurrent tumor as determined by the performing neurosurgeon. Surgical resection/debulking prior to MLA is allowed per standard of care but is not required. 8. Candidate for Optune GIO® therapy. 9. Candidate for pembrolizumab. 10. Adequate bone marrow and organ function as defined below: 1. ANC ≥ 1,500/mcL 2. Platelets ≥ 100,000/mcL 3. Hemoglobin ≥ 9 g/dL or ≥ 5.6 mmol/L (transfusion is allowed) 4. Serum creatinine ≤ 1.5 x IULN OR creatinine clearance by Cockcroft-Gault ≥ 60 mL/min for patients with serum creatinine \> 1.5 x IULN 5. Serum total bilirubin ≤ 1.5 x IULN OR direct bilirubin ≤ IULN for patients with total bilirubin \> 1.5 x IULN 6. AST (SGOT) ≤ 3 x IULN 7. ALT (SGPT) ≤ 3 x IULN 11. Participants of childbearing age must use effective contraception: 1. WOCBP include any woman who has experienced menarche and who has not undergone successful surgical sterilization (hysterectomy, bilateral tubal ligation or oophorectomy) or who is not post-menopausal. Post-menopause is defined as: * Amenorrhea that has lasted for ≥ 12 consecutive months without another cause, or * For women with irregular menstrual periods who are taking hormone replacement therapy (HRT), a documented serum follicle-stimulating hormone (FSH) level of greater than 35 mIU/mL. 2. Males with female partners of childbearing potential must agree to use physician-approved contraceptive methods (e.g., abstinence, condoms, vasectomy) throughout the study and should avoid conceiving children for 24 weeks following the last dose of study drug. 12. Ability of the patient to understand and willingness to sign an IRB approved written informed consent document	1. Prior treatment with any anti-angiogenic agent, including bevacizumab. 2. Prior treatment with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or anti-cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) antibody (including ipilimumab or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways). 3. Prior treatment with a monoclonal antibody within 4 weeks prior to the projected first dose of pembrolizumab or has not recovered (i.e. ≤ grade 1 or at baseline) from adverse events due to agents administered more than 4 weeks earlier. 4. Prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to the projected first dose of pembrolizumab or has not recovered (i.e. ≤ grade 1 or at baseline) from adverse events due to a previously administered agent. 5. Presence of infratentorial lesions, brainstem lesions, or lesions that are less than 5 mm from the hypophysis or cranial nerves. 6. Multifocal gliomas that are bilateral. Patients with unilateral multifocal gliomas may be eligible if their multifocal disease can be treated effectively and safely in a single MLA procedure. Also note that corpus callosal tumors are eligible even if they are bilateral as long as they satisfy the size and shape limits of MLA as determined by the performing neurosurgeon. 7. Presence of leptomeningeal metastases beyond the cranial vault. (Focal leptomeningeal enhancement allowable at the discretion of the principal investigator). 8. Requires corticosteroids equivalent to \> 4mg dexamethasone daily. 9. Recent (within 8 weeks) history of CNS hemorrhage unless the hemorrhage is located within the tumor that will be removed en total during surgical debulking or ablated during MLA. 10. Requires therapeutic doses of anticoagulants unless anticoagulation can be safely discontinued per standard practice (e.g. first DVT for which anticoagulation has been at least 3 months and repeat imaging demonstrates resolution of DVT) or an IVC filter can be used in place of anticoagulation. 11. Received prior local therapy (stereotactic radiosurgery, brachytherapy, or carmustine wafers) to the proposed area of MLA treatment. 12. Received a live vaccine within 30 days prior to the projected initiation of study treatment (Optune GIO® for Arm 1 and LITT for Arm 2). 13. Currently receiving any other investigational agents or has participated in a study of an investigational agent or using an investigational device within 3 weeks of the projected initiation of study treatment (Optune GIO® for Arm 1 and LITT for Arm 2). 14. Has a diagnosis of immunodeficiency or is receiving any form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment (with the exception of daily dexamethasone ≤ 4 mg). 15. Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, uncontrolled hypertension, or psychiatric illness/social situations that would limit compliance with study requirements. 16. History of active autoimmune disease requiring systemic treatment within the past 2 years (i.e. with use of disease modifying agents, corticosteroids, or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment. 17. History of (non-infectious) pneumonitis within the past 3 years that required steroids or current pneumonitis. 18. Pregnant and/or breastfeeding. Patient must have a negative serum or urine pregnancy test within 72 hours of study entry. 19. Known active hepatitis B (e.g., HBsAg reactive) or hepatitis C (e.g., HCV RNA \[qualitative\] is detected) infection. 20. Known history of active TB (bacillus tuberculosis). 21. Known history of HIV (HIV 1/2 antibodies).

Inclusion Criteria

Exclusion Criteria

1. Patient must be at least 18 years of age.
2. Diagnosis of recurrent or progressive glioblastoma, WHO Grade IV, IDH wild-Type or astrocytoma WHO grade IV.
3. Unequivocal evidence of tumor progression by brain MRI scan per RANO criteria. Patients who experience a second disease progression are eligible provided that they have not been previously treated with anti-angiogenic agents including bevacizumab (at the exception of bevacizumab radiation necrotic protocol)
4. A diagnostic contrast-enhanced MRI of the brain must be performed preoperatively, within 28 days prior to study enrollment.
5. There must be an interval of at least 12 weeks from the completion of radiation therapy to study registration unless there is unequivocal evidence for tumor recurrence per RANO criteria. When the interval is less than 12 weeks but more than 4 weeks from the completion of radiotherapy, the use of perfusion imaging and/or PET scan is allowed to differentiate between unequivocal evidence of tumor recurrence and pseudoprogression.
6. Karnofsky performance status (KPS) ≥60%.
7. Candidate for MLA based on the size, location, and shape of the recurrent tumor as determined by the performing neurosurgeon. Surgical resection/debulking prior to MLA is allowed per standard of care but is not required.
8. Candidate for Optune GIO® therapy.
9. Candidate for pembrolizumab.
10. Adequate bone marrow and organ function as defined below:
1. ANC ≥ 1,500/mcL
2. Platelets ≥ 100,000/mcL
3. Hemoglobin ≥ 9 g/dL or ≥ 5.6 mmol/L (transfusion is allowed)
4. Serum creatinine ≤ 1.5 x IULN OR creatinine clearance by Cockcroft-Gault ≥ 60 mL/min for patients with serum creatinine \> 1.5 x IULN
5. Serum total bilirubin ≤ 1.5 x IULN OR direct bilirubin ≤ IULN for patients with total bilirubin \> 1.5 x IULN
6. AST (SGOT) ≤ 3 x IULN
7. ALT (SGPT) ≤ 3 x IULN
11. Participants of childbearing age must use effective contraception:
1. WOCBP include any woman who has experienced menarche and who has not undergone successful surgical sterilization (hysterectomy, bilateral tubal ligation or oophorectomy) or who is not post-menopausal. Post-menopause is defined as:
* Amenorrhea that has lasted for ≥ 12 consecutive months without another cause, or
* For women with irregular menstrual periods who are taking hormone replacement therapy (HRT), a documented serum follicle-stimulating hormone (FSH) level of greater than 35 mIU/mL.
2. Males with female partners of childbearing potential must agree to use physician-approved contraceptive methods (e.g., abstinence, condoms, vasectomy) throughout the study and should avoid conceiving children for 24 weeks following the last dose of study drug.
12. Ability of the patient to understand and willingness to sign an IRB approved written informed consent document

1. Prior treatment with any anti-angiogenic agent, including bevacizumab.
2. Prior treatment with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or anti-cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) antibody (including ipilimumab or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways).
3. Prior treatment with a monoclonal antibody within 4 weeks prior to the projected first dose of pembrolizumab or has not recovered (i.e. ≤ grade 1 or at baseline) from adverse events due to agents administered more than 4 weeks earlier.
4. Prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to the projected first dose of pembrolizumab or has not recovered (i.e. ≤ grade 1 or at baseline) from adverse events due to a previously administered agent.
5. Presence of infratentorial lesions, brainstem lesions, or lesions that are less than 5 mm from the hypophysis or cranial nerves.
6. Multifocal gliomas that are bilateral. Patients with unilateral multifocal gliomas may be eligible if their multifocal disease can be treated effectively and safely in a single MLA procedure. Also note that corpus callosal tumors are eligible even if they are bilateral as long as they satisfy the size and shape limits of MLA as determined by the performing neurosurgeon.
7. Presence of leptomeningeal metastases beyond the cranial vault. (Focal leptomeningeal enhancement allowable at the discretion of the principal investigator).
8. Requires corticosteroids equivalent to \> 4mg dexamethasone daily.
9. Recent (within 8 weeks) history of CNS hemorrhage unless the hemorrhage is located within the tumor that will be removed en total during surgical debulking or ablated during MLA.
10. Requires therapeutic doses of anticoagulants unless anticoagulation can be safely discontinued per standard practice (e.g. first DVT for which anticoagulation has been at least 3 months and repeat imaging demonstrates resolution of DVT) or an IVC filter can be used in place of anticoagulation.
11. Received prior local therapy (stereotactic radiosurgery, brachytherapy, or carmustine wafers) to the proposed area of MLA treatment.
12. Received a live vaccine within 30 days prior to the projected initiation of study treatment (Optune GIO® for Arm 1 and LITT for Arm 2).
13. Currently receiving any other investigational agents or has participated in a study of an investigational agent or using an investigational device within 3 weeks of the projected initiation of study treatment (Optune GIO® for Arm 1 and LITT for Arm 2).
14. Has a diagnosis of immunodeficiency or is receiving any form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment (with the exception of daily dexamethasone ≤ 4 mg).
15. Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, uncontrolled hypertension, or psychiatric illness/social situations that would limit compliance with study requirements.
16. History of active autoimmune disease requiring systemic treatment within the past 2 years (i.e. with use of disease modifying agents, corticosteroids, or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.
17. History of (non-infectious) pneumonitis within the past 3 years that required steroids or current pneumonitis.
18. Pregnant and/or breastfeeding. Patient must have a negative serum or urine pregnancy test within 72 hours of study entry.
19. Known active hepatitis B (e.g., HBsAg reactive) or hepatitis C (e.g., HCV RNA \[qualitative\] is detected) infection.
20. Known history of active TB (bacillus tuberculosis).
21. Known history of HIV (HIV 1/2 antibodies).

Contacts and Locations

Study Contact

Victoria Hope

CONTACT

352-273-9000

victoria.hope@neurosurgery.ufl.edu

Principal Investigator

Ashley Ghiaseddin, MD

PRINCIPAL_INVESTIGATOR

University of Florida

Study Locations (Sites)

UF Health Shands Hospital

Gainesville, Florida, 32608

United States

Collaborators and Investigators

Sponsor: University of Florida

Ashley Ghiaseddin, MD, PRINCIPAL_INVESTIGATOR, University of Florida

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 Date2024-11-12

Study Completion Date2029-10

Study Record Updates

Study Start Date2024-11-12

Study Completion Date2029-10

Terms related to this study

Additional Relevant MeSH Terms

Recurrent Glioblastoma