Status:
ENROLLING_BY_INVITATION
Intrathecal Azacitidine and Nivolumab in Patients With Recurrent High-grade Glioma
Lead Sponsor:
Andrew P. Groves
Conditions:
Glioblastoma (GBM)
Diffuse Midline Glioma (DMG)
Eligibility:
All Genders
13+ years
Phase:
PHASE1
Brief Summary
This is a single-arm open-label phase 1 dose escalation/expansion trial assessing the safety and efficacy of concurrent intrathecal azacitidine and intrathecal nivolumab in recurrent high-grade glioma...
Detailed Description
PRIMARY OUTCOME Phase I To determine the safety and maximum tolerated dose (MTD) of intrathecal (IT) azacitidine in combination with IT nivolumab in patients with recurrent high-grade glioma Expansio...
Eligibility Criteria
Inclusion
- INCLUSION CRITERIA
- For patients age ≥ 18: Able and willing to provide written informed consent
- For patients aged 13-17: Parent/guardian of adolescent patient must have the ability to provide written informed consent. Adolescent patients must have the ability to provide written informed assent.
- Stated willingness to comply with all trial procedures and availability for the duration of the trial
- Histologically confirmed diagnosis of World Health Organization Grade IV high-grade glioma. Eligible diagnoses include: Glioblastoma (IDH-wildtype), Gliosarcoma, Diffuse Midline Glioma (H3 K27-altered), diffuse hemispheric glioma (H3 G34-mutant), diffuse pediatric-type high-grade glioma (H3 and IDH-wildtype), Astrocytoma IDH-mutant (Grade 4)
- Previous first-line treatment with at least radiotherapy (and temozolomide in the case of glioblastoma or astrocytoma IDH-mutant (grade 4))
- Documented recurrence by diagnostic biopsy or contrast-enhanced magnetic resonance imaging (MRI) per RANO 2.0 criteria
- At least one measurable lesion per RANO 2.0 meeting the following criteria: Contrast-enhancing or non-enhancing lesions with clearly defined margins by MRI Scan, with both perpendicular diameters on a single slice of at least 10 mm, visible on two or more slices that are preferably, at most, 3 mm apart with 0-mm interslice gap.
- Age ≥ 13
- Eastern Cooperative Oncology Group (ECOG) performance status of 0-2 (age ≥ 16) or Lansky of ≥ 60 (age \<16)
- Disease status confirmed with baseline imaging performed within 28 days of Day 1 of trial treatment. Patients with extracranial metastatic or leptomeningeal disease will be excluded (see Section 5.2)
- Subjects must be on a stable or decreasing dose of corticosteroids for at least 7 days before enrollment
- Patients must have organ and marrow function as defined below:
- Eligibility Guidelines of Organ and Marrow Function Hematologic Absolute neutrophil count (ANC) ≥ 1.5 x 109/L Hemoglobin ≥ 9.0 g/dL Platelets ≥ 75 x 109/L PT/INR and PTT ≤ 1.5 X ULN Hepatic Total bilirubin ≤ 1.5 X ULN (except subjects with known Gilbert syndrome, who can have total bilirubin \< 3.0 mg/dL AST and ALT ≤ 3.0 X ULN Renal Creatinine OR Calculated creatinine clearance OR 24-hour urine creatinine clearance ≤ 2 X ULN
- 50 mL/min
- 50 ml/min
- Women of childbearing potential (WOCBP) must have a negative serum or urine pregnancy test within 24 hours of starting therapy
- WOCBP must agree to follow instructions for methods of contraception
- Men who are sexually active with WOCBP must agree to follow instructions for methods of contraception
- Investigators will counsel WOCBP and male subjects who are sexually active with WOCBP on the importance of pregnancy prevention and implications of an unexpected pregnancy. At a minimum subjects must agree to the use of two methods of contraception, with one method being highly effective and the other method being either highly effective or less effective: starting at ICF or first dose and continuing 6 months after last dose of trial treatment:
- Highly effective methods of contraception Male condoms with spermicide Hormonal methods including combined oral contraceptive pills, vaginal ring, injectables, implants, and intrauterine devices (IUD) Non-hormonal IUD Tubal ligation Vasectomy Complete Abstinence
- Less effective methods of contraception Diaphragm with spermicide Cervical cap with spermicide Vaginal sponge Male condom without spermicide Progestin only pills Female condom
- An interval of ≥ 2 weeks from major surgery
- An interval of ≥ 4 weeks from chemotherapy, radiotherapy, or other investigational agents
- EXCLUSION CRITERIA
- Presence of extracranial metastatic or leptomeningeal disease
- Patients with diffuse intrinsic pontine glioma, defined as tumors with a pontine epicenter and diffuse involvement of the pons
- Patients must not have active autoimmune disease that has required systemic treatment in the past 2 years (e.g. use of disease modifying agents, corticosteroids, or immunosuppressive drugs)
- Prior azacitidine for the treatment of cancer (prior administration of nivolumab or other immune checkpoint inhibitor is allowed)
- Subjects with major medical, neurologic, or psychiatric condition who are judged to be unable to fully comply with trial therapy or assessments
- Positive test for hepatitis B or C virus indicating acute or chronic infection, given the risk of reactivation with checkpoint inhibition
- Known history of testing positive for HIV or known acquired immunodeficiency syndrome (AIDS), due to the unknown effects of HIV on the immune response to intrathecal azacitidine and nivolumab
- Patients with a history of pneumonitis
- Evidence of active infection requiring treatment with IV antibiotics ≤ 7 days prior to initiation of trial therapy.
- History of allergy to trial drug components
- Prisoners or subjects involuntarily incarcerated
- Patients of all genders, races, and ethnicities are invited to participate.
Exclusion
Key Trial Info
Start Date :
June 5 2025
Trial Type :
INTERVENTIONAL
Allocation :
ESTIMATED
End Date :
March 1 2027
Estimated Enrollment :
34 Patients enrolled
Trial Details
Trial ID
NCT06896110
Start Date
June 5 2025
End Date
March 1 2027
Last Update
June 26 2025
Active Locations (1)
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1
Holden Comprehensive Cancer Center
Iowa City, Iowa, United States, 52242