Trial Title:
D2C7-IT and 2141-V11 in Newly Diagnosed GBM Patients
NCT ID:
NCT05734560
Condition:
Newly Diagnosed MGMT Unmethylated Glioblastoma
Conditions: Official terms:
Glioblastoma
D2C7-(scdsFv)-PE38KDEL
Conditions: Keywords:
D2C7
D2C7-IT
2141-V11
Pro00110119
GBM
Glioblastoma
convection-enhanced delivery
CED
MGMT unmethylated
Study type:
Interventional
Study phase:
Phase 1/Phase 2
Overall status:
Recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
D2C7-IT
Description:
D2C7-IT will be dosed at 166,075 ng in 36 mL.
Arm group label:
D2C7-IT + 2141-V11
Intervention type:
Drug
Intervention name:
2141-V11
Description:
2141-V11 will be dosed at 3 mg in 3.5 mL for CED administration. 2141-V11 in the cervical
perilymphatic subcutaneous area will be dosed at 2 mg.
Arm group label:
D2C7-IT + 2141-V11
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).
Detailed description:
Within this study, approximately 50 study participants will receive a single infusion of
D2C7-IT in the hospital, which is delivered to the tumor margins over 3 days through a
catheter placed in the brain, followed by a single infusion of 2141-V11 delivered over 7
hours to the tumor margins through the same catheter. About 2 weeks after intratumoral
infusion of D2C7-IT and 2141-V11, participants will have their first subcutaneous (under
the skin) injection of 2141-V11 in the area around the lymph nodes of the head and neck
on the same side as the tumor. About a week after this injection, participants will start
standard radiation therapy (RT), which typically lasts either 3 weeks or 6 weeks
depending upon age. Once RT is finished, participants will resume injections in the area
around the lymph nodes of the head and neck on the same side as the tumor of 2141-V11
about 1 week later. They will have another injection about 3 weeks after finishing RT and
then start a schedule of injections about every 3 weeks for up to a year.
There are risks to the study drugs that are described in this document. Some common risks
related to D2C7-IT include: effects related to tumor cells dying (tumor necrosis),
effects on normal brain tissue, effects related to catheter placement and removal,
effects related to fluid infusion into the brain (intracerebral infusion), and reactions
to the D2C7-IT being directly infused in your brain. Risks of 2141-V11 being directly
infused in your brain and injected in the area around the lymph nodes of the head and
neck could include: cytokine release syndrome (release of immune system cells called
cytokines that can cause fever, chills, headache, muscle pain, itching, rash, chest
tightness, palpitations, shortness of breath, low blood pressure, nausea, vomiting),
swelling and redness in the neck area, overstimulation of your immune system such that it
attacks other tissues in your body, elevated liver enzymes, and low platelets in the
blood.
Criteria for eligibility:
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)
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Duke University Medical Center
Address:
City:
Durham
Zip:
27710
Country:
United States
Status:
Recruiting
Contact:
Last name:
Annick Desjardins, MD
Phone:
919-684-5301
Email:
dukebrain1@dm.duke.edu
Contact backup:
Last name:
Stevie Threatt
Phone:
919-684-5301
Email:
dukebrain1@dm.duke.edu
Investigator:
Last name:
Annick Desjardins, MD
Email:
Principal Investigator
Start date:
September 6, 2023
Completion date:
February 2028
Lead sponsor:
Agency:
Darell Bigner
Agency class:
Other
Collaborator:
Agency:
Rockefeller University
Agency class:
Other
Source:
Duke University
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05734560
https://tischbraintumorcenter.duke.edu/
https://www.dukehealth.org/clinical-trials
