D2C7-IT and 2141-V11 in Newly Diagnosed GBM Patients

• Status: Not yet recruiting
• Trial end date: 2028-02-01
• Target enrollment: 0
• Participant gender: All

Summary

The purpose of this research study is to determine the safety and efficacy of administering a single intracerebral (within the brain) dose of investigational compounds called D2C7-immunotoxin (IT) and 2141-V11 in residual disease (within tumor margins) after surgery, followed by later repeated injections of 2141-V11 in the subcutaneous area (under the skin) around the lymph nodes of the head and neck for adults newly diagnosed with a type of cancerous brain tumor called glioblastoma. The word "investigational" means the study drugs are still being tested in research studies and are not approved by the U.S. Food and Drug Administration (FDA).

• Phase: Phase 1/Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Darell Bigner
• Collaborator: Rockefeller University

Criteria

Inclusion Criteria:

1. Age ≥ 18 years of age at the time of entry into the study

2. Newly diagnosed supratentorial glioblastoma, WHO grade 4, IDH wildtype, MGMT unmethylated (high grade glioma with molecular features of glioblastoma will be eligible under WHO 4 malignant glioma) with definitive resection prior to enrollment, with residual radiographic non-contrast enhancing disease on the post-operative CT or MRI of amenable to catheter placement. The residual radiographic contrast enhancing disease is ≤ 3 cm in maximal diameter in any plane.

3. Able to receive standard of care RT (typically 59.4-60 Gy over approximately 6 weeks duration if under 65 years old and a minimum of 40 Gy over 3 weeks duration if 65 years or older)

4. Karnofsky Performance Score (KPS) > 70%

5. Hemoglobin ≥ 9 g/dl prior to catheter placement

6. Platelet count ≥ 100,000/µL unsupported. 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

7. Neutrophil count ≥ 1000 prior to catheter placement

8. Creatinine ≤ 1.5 x normal range prior to catheter placement

9. Total bilirubin ≤ 1.5 x ULN prior to catheter placement (Exception: Participant has known or 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.)

10. AST/ALT ≤ 2.5 x ULN

11. Prothrombin and Partial Thromboplastin Times ≤ 1.2 x normal 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.

12. 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 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 (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

13. 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

Exclusion Criteria:

1. Females who are pregnant or breast-feeding

2. Patients with an impending, life-threatening cerebral herniation syndrome, based on the assessment of the study neurosurgeons or their designate

3. Patients with severe, active comorbidity, defined as follows:

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 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

5. Patients with uncontrolled diabetes mellitus

6. Patients with albumin allergy

7. Patients with known hepatic insufficiency resulting in clinical jaundice and/or coagulation defects

8. Patients with known HIV or Hepatitis C positive status

9. Major medical illnesses or psychiatric impairments that, in the investigator's opinion, will prevent administration or completion of protocol therapy

4. Patients who previously received other conventional therapeutic interventions for newly diagnosed glioblastoma with the exception of surgical resection for the brain tumor

5. Patients with evidence of tumor in the brainstem, cerebellum, or spinal cord, radiological evidence of (actively growing) multifocal disease, tumor crossing the midline, extensive subependymal disease, or leptomeningeal disease

6. Patients on greater than 4 mg per day of dexamethasone within the 2 weeks prior to the D2C7-IT infusion

7. Patients with worsening steroid myopathy (history of gradual progression of bilateral proximal muscle weakness, and atrophy of proximal muscle groups)

8. 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

9. Patients with active autoimmune disease requiring systemic immunomodulatory treatment within the past 3 months

10. Patients who cannot undergo MRI due to obesity or to having certain metal in their bodies (i.e. pacemakers, infusion pumps, metal aneurysm clips, metal prostheses, joints, rods, or plates)