Malignant GliomaPhase 1NCT04160494
D2C7-IT With Atezolizumab for Recurrent Gliomas
A Phase 1 study testing D2C7-IT (6920 ng/mL via convection-enhanced delivery), Atezolizumab (1200 mg every three weeks) and D2C7-IT (4613.2 ng/mL via convection-enhanced delivery) in people with Malignant Glioma, run by Darell Bigner at 1 site in United States.
Trial summary
This is a phase 1 study of atezolizumab in combination with D2C7-IT, a dual-specific monoclonal antibody (mAB) with a high affinity for both EGFRwt- and EGFRvIII-expressing cells, in patients with recurrent World Health Organization (WHO) grade IV malignant glioma at the Preston Robert Tisch Brain Tumor Center… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Malignant Glioma
- What is being tested?
- D2C7-IT (6920 ng/mL via convection-enhanced delivery), Atezolizumab (1200 mg every three weeks) and D2C7-IT (4613.2 ng/mL via convection-enhanced delivery)
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 14 participants
- Where
- 1 siteUnited States
- Study dates
- 25 Feb 2020to 11 Jun 2026
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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:
- 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,
- 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
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- 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
Who cannot join
- 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:
- Patients with an active infection requiring intravenous treatment or having an unexplained febrile illness (Tmax > 99.5°F/37.5°C)
- Patients with known immunosuppressive disease or known human immunodeficiency virus infection
- Patients with unstable or severe intercurrent medical conditions such as severe heart disease (New York Heart Association Class 3 or 4)
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- Patients with known lung (forced expiratory volume in the first second of expiration (FEV1) < 50%) disease or uncontrolled diabetes mellitus
- Patients with albumin allergy
- 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)
- 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
- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
Duke University Medical Center
Durham, North Carolina, 27710
About this study
Official title: A Phase 1 Trial of D2C7-IT in Combination With Atezolizumab in Recurrent WHO Grade IV Malignant Glioma
This is a phase 1 study of atezolizumab in combination with D2C7-IT, a dual-specific monoclonal antibody (mAB) with a high affinity for both EGFRwt- and EGFRvIII-expressing cells, in patients with recurrent World Health Organization (WHO) grade IV malignant glioma at the Preston Robert Tisch Brain Tumor Center (PRTBTC) at Duke.
Read the detailed description
Approximately eighteen patients with recurrent WHO grade IV malignant glioma will receive atezolizumab and D2C7-IT to determine the impact of the combination of D2C7-IT and atezolizumab on safety. D2C7-IT will be delivered intratumorally by Convection Enhanced Delivery (CED) using an intracerebral catheter placed within the enhancing portion of the tumor. The dose of D2C7-IT was reduced from 6920 ng/mL to 4613.2 ng/mL after the first 4 patients as a precaution due to safety events experienced by these 4 patients.
Atezolizumab will be administered according to the FDA-approved dosing schedule of 1200 mg intravenously every 3 weeks, beginning ~2 weeks after the D2C7-IT infusion.
Toxicity will be carefully monitored for each patient while they are on study for at least a year after D2C7-IT treatment or for at least 30 days after the final dose of atezolizumab if the patient continues atezolizumab on-study for longer than a year post-D2C7-IT. Of particular interest will be the incidence of adverse events that occur during the first 28 days after D2C7-IT treatment and the inflammatory events that occur during the first year after D2C7-IT treatment.
The most common risks associated with D2C7-IT are effects related to tumor necrosis, neurologic changes (including changes in function, new or increased seizures, swelling of the brain, and injury to blood vessels), effects related to catheter placement or removal, and effects related to fluid infusion into the brain. The most common risks associated with atezolizumab are fatigue, decreased appetite, diarrhea, and nausea. Because atezolizumab works with the immune system, it can cause the immune system to attack normal organs or tissue and affect how they work.
- Conditions
- Malignant Glioma
- Being tested
- D2C7-IT (6920 ng/mL via convection-enhanced delivery), Atezolizumab (1200 mg every three weeks), D2C7-IT (4613.2 ng/mL via convection-enhanced delivery)
- Keywords
- D2C7, D2C7-IT, Atezolizumab, Randazzo, Glioblastoma, Glioma, Bigner, Pro00101898, Genentech, CTEP, Duke, Landi
- Medical subject headings
- Glioma, Glioblastoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
D2C7-IT (6920 ng/mL via convection-enhanced delivery)Drug
dual-specific mAB
Atezolizumab (1200 mg every three weeks)Drug
Also called Tecentriq
programmed cell death ligand 1 (PD-L1) blocking antibody
D2C7-IT (4613.2 ng/mL via convection-enhanced delivery)Drug
dual-specific mAB
| Study group | Role | What they receive |
|---|---|---|
| D2C7-IT (6920 ng/mL) + Atezolizumab | Experimental | Single D2C7-IT convection-enhanced delivery (CED) infusion (6920 ng/mL) plus atezolizumab (1200 mg) intravenous (IV) infusions every three weeks for up to two years Receives: Drug: D2C7-IT (6920 ng/mL via convection-enhanced delivery); Drug: Atezolizumab (1200 mg every three weeks) |
| D2C7-IT (4613.2 ng/mL) + Atezolizumab | Experimental | Single D2C7-IT convection-enhanced delivery (CED) infusion (4613.2 ng/mL) plus atezolizumab (1200 mg) intravenous (IV) infusions every three weeks for up to two years Receives: Drug: Atezolizumab (1200 mg every three weeks); Drug: D2C7-IT (4613.2 ng/mL via convection-enhanced delivery) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Proportion of patients with an unacceptable adverse event
An unacceptable adverse event includes any Grade 3 or any Grade 4 toxicity that is not reversible within 2 weeks, any life-threatening event, or any treatment-related death. Also included are any grade 2 or higher serious autoimmune toxicities, particularly those affecting vital organs (e.g. cardiac, renal, CNS) if it occurs within 2 weeks of any protocol treatment.
Measured: 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Nov 2019
- Study start25 Feb 2020
- Primary completion28 Jun 2024
- Study completion11 Jun 2026
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Malignant GliomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 14 participants (actual)
Sponsor and investigators
- Lead sponsor
- Darell Bigner
- Sponsor type
- University, hospital or other
- Collaborators
- Istari Oncology, Inc., National Cancer Institute (NCI), Genentech, Inc.
- Responsible party
- Sponsor-investigator, Darell Bigner, Duke University
- Investigators
- Annick Desjardins, MD, Principal investigator, Duke University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04160494
- Sponsor's protocol ID
- Pro00101898
- Other IDs
- FOR0003
- Status last verified
- Oct 2026
- First submitted
- 8 Nov 2019
- Last updated
- 14 Oct 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 14 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1 Trial of D2C7-IT in Combination With Atezolizumab in Recurrent WHO Grade IV Malignant Glioma
- ClinicalTrials.gov ID
- NCT04160494
- Acronym / sponsor ID
- Pro00101898
- Conditions
- Malignant Glioma
- Keywords
- D2C7, D2C7-IT, Atezolizumab, Randazzo, Glioblastoma, Glioma, Bigner, Pro00101898
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 14 participants (actual)
- Lead sponsor
- Darell BignerUniversity, hospital or other
- Collaborators
- Istari Oncology, Inc., National Cancer Institute (NCI), Genentech, Inc.
- Study start
- 25 Feb 2020 (actual)
- Primary completion
- 28 Jun 2024 (actual)
- Study completion
- 11 Jun 2026 (actual)
- First posted
- 13 Nov 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a phase 1 study of atezolizumab in combination with D2C7-IT, a dual-specific monoclonal antibody (mAB) with a high affinity for both EGFRwt- and EGFRvIII-expressing cells, in patients with recurrent World Health Organization (WHO) grade IV malignant glioma at the Preston Robert Tisch Brain Tumor Center (PRTBTC) at Duke.
Detailed description
Approximately eighteen patients with recurrent WHO grade IV malignant glioma will receive atezolizumab and D2C7-IT to determine the impact of the combination of D2C7-IT and atezolizumab on safety. D2C7-IT will be delivered intratumorally by Convection Enhanced Delivery (CED) using an intracerebral catheter placed within the enhancing portion of the tumor. The dose of D2C7-IT was reduced from 6920 ng/mL to 4613.2 ng/mL after the first 4 patients as a precaution due to safety events experienced by these 4 patients.
Atezolizumab will be administered according to the FDA-approved dosing schedule of 1200 mg intravenously every 3 weeks, beginning ~2 weeks after the D2C7-IT infusion.
Toxicity will be carefully monitored for each patient while they are on study for at least a year after D2C7-IT treatment or for at least 30 days after the final dose of atezolizumab if the patient continues atezolizumab on-study for longer than a year post-D2C7-IT. Of particular interest will be the incidence of adverse events that occur during the first 28 days after D2C7-IT treatment and the inflammatory events that occur during the first year after D2C7-IT treatment.
The most common risks associated with D2C7-IT are effects related to tumor necrosis, neurologic changes (including changes in function, new or increased seizures, swelling of the brain, and injury to blood vessels), effects related to catheter placement or removal, and effects related to fluid infusion into the brain. The most common risks associated with atezolizumab are fatigue, decreased appetite, diarrhea, and nausea. Because atezolizumab works with the immune system, it can cause the immune system to attack normal organs or tissue and affect how they work.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| D2C7-IT (6920 ng/mL) + Atezolizumab | Experimental | Drug: D2C7-IT (6920 ng/mL via convection-enhanced delivery), Drug: Atezolizumab (1200 mg every three weeks)Single D2C7-IT convection-enhanced delivery (CED) infusion (6920 ng/mL) plus atezolizumab (1200 mg) intravenous (IV) infusions every three weeks for up to two years |
| D2C7-IT (4613.2 ng/mL) + Atezolizumab | Experimental | Drug: Atezolizumab (1200 mg every three weeks), Drug: D2C7-IT (4613.2 ng/mL via convection-enhanced delivery)Single D2C7-IT convection-enhanced delivery (CED) infusion (4613.2 ng/mL) plus atezolizumab (1200 mg) intravenous (IV) infusions every three weeks for up to two years |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (17 listed)
- 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:
- Age ≥ 18 years of age at the time of entry into the study
- Karnofsky Performance Score (KPS) ≥ 70%
Key exclusion criteria (21 listed)
- 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:
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| D2C7-IT (6920 ng/mL via convection-enhanced delivery)dual-specific mAB | Drug | D2C7-IT (6920 ng/mL) + Atezolizumab |
| Atezolizumab (1200 mg every three weeks)Also: Tecentriqprogrammed cell death ligand 1 (PD-L1) blocking antibody | Drug | D2C7-IT (4613.2 ng/mL) + Atezolizumab, D2C7-IT (6920 ng/mL) + Atezolizumab |
| D2C7-IT (4613.2 ng/mL via convection-enhanced delivery)dual-specific mAB | Drug | D2C7-IT (4613.2 ng/mL) + Atezolizumab |
Primary outcome
Proportion of patients with an unacceptable adverse event
Time frame: 2 years
An unacceptable adverse event includes any Grade 3 or any Grade 4 toxicity that is not reversible within 2 weeks, any life-threatening event, or any treatment-related death. Also included are any grade 2 or higher serious autoimmune toxicities, particularly those affecting vital organs (e.g. cardiac, renal, CNS) if it occurs within 2 weeks of any protocol treatment.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Oct 2026.
- The Preston Robert Tisch Brain Tumor CenterLink provided by the sponsor.
- Duke HealthLink provided by the sponsor.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Annick Desjardins, MD principal investigator
Duke University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing D2C7-IT (6920 ng/mL via convection-enhanced delivery), Atezolizumab (1200 mg every three weeks) and D2C7-IT (4613.2 ng/mL via convection-enhanced delivery) in people with Malignant Glioma, run by Darell Bigner at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 17 inclusion and 21 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 14 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Proportion of patients with an unacceptable adverse event (time frame: 2 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Oct 2026.