Inclusion Criteria:
- - Patients must have a recurrent supratentorial WHO grade IV malignant glioma based on
imaging studies.
- - Prior histopathology confirmed recurrent supratentorial WHO grade IV malignant
glioma.
- - Patient or partner(s) meets one of the following criteria:
1.
Non-childbearing potential (i.e. not sexually active, physiologically incapable
of becoming pregnant, including any female who is post-menopausal or surgically
sterile, or any male who has had a vasectomy). Surgically sterile females are
defined as those with a documented hysterectomy and/or bilateral oophorectomy
or tubal l ligation. Postmenopausal for purposes of this study is defined as 1
year without menses; or,
2. Childbearing potential and agrees to use one of the following methods of birth
control: approved hormonal contraceptives that do not contain estrogen (e.g.,
birth control pills, patches, implants, or infusions), an intrauterine device,
or a barrier method of contraception (e.g., a condom or diaphragm) used with
spermicide.
- - Age ≥ 18 years of age at the time of entry into the study.
- - Karnofsky Performance Score (KPS) ≥ 70%
- Hemoglobin ≥ 9 g/dl prior to biopsy.
- - Platelet count ≥ 100,000/µl unsupported is necessary for eligibility on the study;
however, because of risks of intracranial hemorrhage with catheter placement,
platelet count ≥ 125,000/µl is required for the patient to undergo biopsy and
catheter insertion, which can be attained with the help of platelet transfusion.
- - Neutrophil count ≥ 1000 cells/mm3 prior to biopsy.
- - Creatinine ≤ 1.5 x upper limit of normal (ULN) range prior to biopsy.
- - Total bilirubin ≤ 1.5 x ULN prior to biopsy, s (Exception: Patient has known
Gilbert's Syndrome or patient has suspected Gilbert's Syndrome, for which additional
lab testing of direct and/or indirect bilirubin supports this diagnosis.
In these
instances, a total bilirubin of ≤ 3.0 x ULN is acceptable.)
- - AST (aspartate aminotransferase)/ALT (alanine aminotransferase) ≤ 2.5 x ULN prior to
biopsy.
- - Prothrombin and Partial Thromboplastin Times ≤ 1.2 x ULN prior to biopsy.
Patients
with prior history of thrombosis/embolism are allowed to be on anticoagulation,
understanding that anticoagulation will be held in the perioperative period per the
neurosurgical team's recommendations. Low molecular weight heparin (LMWH) is
preferred. If a patient is on warfarin, the international normalized ratio (INR) is
to be obtained and value should be below 2.0 prior to biopsy.
- - At the time of biopsy, prior to administration of D2C7-IT, the presence of recurrent
tumor must be confirmed by histopathological analysis.
- - A signed informed consent form approved by the Institutional Review Board (IRB) will
be required for patient enrollment into the study.
Patients must be able to read and
understand the informed consent document and must sign the informed consent
indicating that they are aware of the investigational nature of this study.
- - Able to undergo brain MRI with and without contrast.
Exclusion Criteria:
- - Females who are pregnant or breast-feeding.
- - Patients with an impending, life-threatening cerebral herniation syndrome, based on
the assessment of the study neurosurgeons or their designate.
- - Patients with severe, active co-morbidity, defined as follow:
1.
Patients with an active infection requiring intravenous treatment or having an
unexplained febrile illness (Tmax > 99.5°F/37.5°C)
2. Patients with known immunosuppressive disease or known human immunodeficiency
virus infection. 3. Patients with unstable or severe intercurrent medical conditions such as severe
heart disease (New York Heart Association Class 3 or 4)
4. Patients with known lung (forced expiratory volume in the first second of
expiration (FEV1) < 50%) disease or uncontrolled diabetes mellitus. 5. Patients with albumin allergy. 6. Patients with severe (i.e., anaphylactic) gadolinium allergy. Patients with
mild allergies (e.g., rash only) will be pretreated with acetaminophen and
diphenhydramine prior to injection of the contrast agent.
- - Patients may not have received chemotherapy or bevacizumab ≤ 4 weeks [except for
nitrosourea (6 weeks) or metronomic dosed chemotherapy such as daily etoposide or
cyclophosphamide (1 week)] prior to starting the study drug unless patients have
recovered from side effects of such therapy.
Patients should discontinue use of
tumor- treating fields (TTFs), such as Optune™, at least one week prior to D2C7-IT
infusion.
- - Patients may not have received immunotherapy ≤ 4 weeks prior to starting the study
drug unless patients have recovered from side effects of such therapy.
- - Patients may not be less than 12 weeks from radiation therapy, unless progressive
disease outside of the radiation field or 2 progressive scans at least 4 weeks apart
or histopathologic confirmation.
- - Patients who have not completed all standard of care treatments, including surgical
procedure and radiation therapy (at least 59 Gy)
1.
If the MGMT promoter in their tumor is known to be unmethylated, patients are
not mandated to have received chemotherapy prior to participating in this trial. 2. If the MGMT promoter in their tumor is known to be methylated or the MGMT
promoter methylation status is unknown at time of screening, patients must have
received at least one chemotherapy regimen prior to participating in this trial.
- - Patients with neoplastic lesions in the brainstem, cerebellum, or spinal cord;
radiological evidence of active (growing) disease (active multifocal disease);
extensive subependymal disease (tumor touching subependymal space is allowed); tumor
crossing the midline or leptomeningeal disease.
- - Patients on greater than 4 mg per day of dexamethasone within the 2 weeks prior to
the D2C7-IT infusion.
- - Patients with worsening steroid myopathy (history of gradual progression of
bilateral proximal muscle weakness, and atrophy of proximal muscle groups)
- Patients with prior, unrelated malignancy requiring current active treatment with
the exception of cervical carcinoma in situ and adequately treated basal cell or
squamous cell carcinoma of the skin.
- - Patients with a known history of hypersensitivity to atezolizumab, or any components
of atezolizumab.
- Patients with active autoimmune disease requiring systemic immunomodulatory
treatment within the past 3 months
