Malignant GliomaPhase 1NCT02303678
D2C7 for Adult Patients With Recurrent Malignant Glioma
A Phase 1 study testing D2C7-IT in people with Malignant Glioma and Brain Tumor, Recurrent, run by Darell Bigner at 1 site in United States.
Trial summary
This is a Phase I study to determine the maximum tolerated dose (MTD) and/or recommended phase II dose of D2C7-IT (D2C7 Immunotoxin) when delivered intratumorally by convection-enhanced delivery (CED) to recurrent World Health Organization (WHO) grade III and IV malignant glioma patients, and/or to determine what dose… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Malignant Glioma, Brain Tumor, Recurrent
- What is being tested?
- D2C7-IT
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 81 participants
- Where
- 1 siteUnited States
- Study dates
- 5 May 2015to 25 Mar 2024
- Phase
- Phase 1
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 III or IV malignant glioma based on imaging studies;
- Prior histopathology consistent with a supratentorial WHO grade III or IV malignant glioma;
- Following biopsy, prior to administration of D2C7-IT, the presence of recurrent tumor must be confirmed by histopathological analysis;
- Age ≥ 18 years of age;
- Karnofsky Performance Status (KPS) ≥ 70%;
- Laboratory Values:
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- 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;
- Hemoglobin ≥ 9 gm/dL prior to biopsy;
- Absolute neutrophil count (ANC) ≥ 1000 cells/mm3 prior to biopsy;
- Serum creatinine ≤ 1.5 x the upper limit of normal (ULN) prior to biopsy;
- Liver Function: Total bilirubin ≤ 1.5 x ULN prior to biopsy (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 the ULN prior to biopsy;
- Prothrombin (PT) and activated Partial Thromboplastin Time (aPTT) ≤ 1.2 x upper limit of normal (ULN) prior to biopsy. Patients with prior history of thrombosis/embolism are allowed to be on anticoagulation, understanding that anti-coagulation will be held in the peri-operative 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;
- Ability to comply with study and follow-up procedures;
- If the patient is a sexually active female of child bearing potential, whose partner is male, or if the patient is a sexually active male, whose partner is a female of child bearing potential, the patient must agree to use appropriate contraceptive measures for the duration of the treatment of the tumor and for 6 months afterwards as stated in the informed consent. Female patients of child bearing potential must have a negative serum pregnancy test at the time of screening and within 48 hours of starting the D2C7-IT infusion
- Patients will sign an IRB-approved informed consent form prior to any study-related procedures.
- Able to undergo brain MRI with and without contrast.
Who cannot join
- 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;
- Pregnant or breastfeeding;
- Patients with contrast-enhancing tumor component crossing the midline, actively growing multi-focal tumor, infratentorial tumor or extensive tumor dissemination (subependymal or leptomeningeal);
- Patients with clinically significant increased intracranial pressure (e.g., impending herniation), uncontrolled seizures, or requirement for immediate palliative treatment;
- Patients with a known severe allergy to Gadolinium-DTPA. Patients with mild allergies (e.g., rash only) will be pretreated with acetaminophen and diphenhydramine prior to injection of the contrast agent;
- Unstable systemic disease in the opinion of the treating physician, for example active infection requiring IV antibiotics;
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- Patients on greater than 4mg per day of dexamethasone within the 2 weeks prior to admission for D2C7-IT infusion;
- Patients with worsening steroid myopathy (history of gradual progression of bilateral proximal muscle weakness, and atrophy of proximal muscle groups);
- Patients who have not completed standard of care treatment prior to participation in this trial, i.e. surgical procedure and radiation therapy (at least 59 Gy). Note: If tumor is unmethylated, patients are not mandated to have received chemotherapy prior to participation in this trial. However, if tumor is methylated, patients must have received at least one chemotherapy regimen prior to participation in this trial.
- 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;
- Treated with immunotherapeutic agents within 4 weeks before enrollment, unless the patient has recovered from the expected toxic effects of such therapy;
- Treated with antiangiogenic agents (like bevacizumab) within 4 weeks before biopsy;
- Treated with alkylating agents within 4 weeks before enrollment (6 weeks for nitrosoureas) or treated within 1 week before enrollment with daily or metronomic chemotherapy, unless the patient has recovered from the expected toxic effects of such therapy;
- Prior chemotherapy (non-alkylating agents) within 2 weeks before enrollment, unless the patient has recovered from the expected toxic effects of such therapy.
Trial locations and contacts
1 site in 1 country.
United States1 site
Preston Robert Tisch Brain Tumor Center at Duke
Durham, North Carolina, 27710
About this study
Official title: Phase I Single-Center, Dose Escalation Study of D2C7-IT Administered Intratumorally Via Convection-Enhanced Delivery for Adult Patients With Recurrent Malignant Glioma
This is a Phase I study to determine the maximum tolerated dose (MTD) and/or recommended phase II dose of D2C7-IT (D2C7 Immunotoxin) when delivered intratumorally by convection-enhanced delivery (CED) to recurrent World Health Organization (WHO) grade III and IV malignant glioma patients, and/or to determine what dose will be considered in a Phase II trial. Patients with recurrent WHO grade III and IV malignant glioma who meet eligibility criteria will be enrolled into the study. Immediately following the stereotactically-guided tumor biopsy conducted as standard of care, up to three additional core biopsies will be obtained for molecular genetic testing. After these biopsies are obtained, subjects will have up to 2 catheters inserted. If the biopsy indicates a proven diagnosis of recurrent malignant glioma (diagnosis results are typically received within 24-48 hours following biopsy), the investigators will proceed with the D2C7-IT infusion. If no tumor is identified, the catheters will be removed. A continuous intratumoral infusion of D2C7-IT will be administered over 72 hours while in the hospital.
Read the detailed description
This is a Phase I study to determine the maximum tolerated dose (MTD) of D2C7-IT, when delivered intratumorally by convection-enhanced delivery (CED) following confirmatory diagnostic biopsy in recurrent World Health Organization (WHO) grade III and IV malignant glioma patients, and/or to determine what dose will be considered in a phase II trial. The patient will remain in the hospital during the entire infusion. At the completion of the infusion, the catheters will be removed within 6 hours and a CT scan will be obtained after the catheters are pulled. The patient will be observed in hospital for a minimum of another 6 hours.
A two-stage continual reassessment method (CRM) design will be used to determine the MTD of D2C7-IT where the first stage involves dose escalation in successive patients until an initial dose-limiting toxicity (DLT) is observed. Cohorts of 2 patients will be accrued to this study within both stages of the trial. The first patient of each cohort will be observed through the completion of the D2C7-IT infusion, before additional patients in that cohort are treated. Once the optimal dose level of D2C7-IT is determined (dose escalation completed), a total of 27 recurrent patients with WHO grade IV malignant glioma patients will be treated at that dose level as a dose expansion cohort.
Following D2C7-IT infusion, subjects will be evaluated in clinic at 2 weeks for adverse events and followed at 4 and 8 weeks and every 8 weeks thereafter until 48 weeks.
- Conditions
- Malignant Glioma, Brain Tumor, Recurrent
- Being tested
- D2C7-IT
- Keywords
- D2C7, Randazzo, Bigner, Pro00053325, recurrent malignant glioma, Landi, Desjardins
- Medical subject headings
- Glioma, Brain Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
D2C7-ITDrug
D2C7-IT is a single-chain fragment variable (scFv) monoclonal antibody (Mab) fragment immunotoxin with high binding affinity for both EGFRwt- and EGFRvIII-expressing glioblastoma multiforme (GBM) cells.
| Study group | Role | What they receive |
|---|---|---|
| D2C7-IT | Experimental | Recurrent malignant glioma patients will receive D2C7-IT, delivered intratumorally by CED following confirmatory diagnostic biopsy. Receives: Drug: D2C7-IT |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximum tolerated dose (MTD) and/or recommended phase II dose of D2C7-IT
The MTD is the dose that results in an estimated DLT rate based upon the CRM model that is nearest to the target DLT rate of 0.25. DLTs include any ≥ Gr.3 non-hematologic toxicities, any ≥ Gr.3 neurological toxicities, and any ≥ Gr.3 hematologic toxicities that do not resolve to pre-treatment baseline or ≤ Gr.1 within 2 weeks or any toxicity that resolves within the 2 week period, but then recurs during that same 2 week period. Adverse events will be collected using Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.
Measured: 2 weeks after D2C7 administration
Secondary outcomes (2)
Overall survival (OS)
OS is defined at the time between administration of D2C7-IT and death. For patients alive, OS will be censored at the time of last follow-up. Kaplan-Meier methods will be used to estimate median OS and PFS.
Measured: 3 years
Association between EGFRvIII and EGFRwt expression and PFS and OS.
Cox proportional hazards models will explore the relationship between EGFRvIII and EGFRwt expression as measured by immunohistochemistry (IHC), polymerase chain reactions (PCR), and fluorescence in situ hybridization (FISH) and PFS and OS.
Measured: 3 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Dec 2014 (estimated)
- Study start5 May 2015
- Primary completion9 May 2019
- Study completion25 Mar 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- 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
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 81 participants (actual)
Sponsor and investigators
- Lead sponsor
- Darell Bigner
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Darell Bigner, Duke University
- Investigators
- Annick Desjardins, MD, FRCPC, Principal investigator, Preston Robert Tisch Brain Tumor Center at Duke University Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02303678
- Sponsor's protocol ID
- Pro00053325
- Status last verified
- Oct 2026
- First submitted
- 19 Nov 2014
- Last updated
- 23 Oct 2026
- Results posted
- No
- Data monitoring committee
- No
Publications
https://www.nature.com/articles/s41591-026-04715-w
Chandramohan V, Herndon JE 2nd, Barnwal A, Ayasoufi K, Yan W, Stevenson K, Bowie ML, Brown MC, Nair SK, Gromeier M, Randazzo D, Peters KB, Johnson MO, McLendon RE, Landi D, Sampson JH, Pastan IH, Friedman AH, Friedman HS, Ashley DM, Bigner DD, Desjardins A. EGFR-targeted antibody-toxin conjugate in recurrent glioma: a phase 1 trial. Nat Med. 2026 Oct 16. doi: 10.1038/s41591-026-04715-w. Online ahead of print.
PubMed 42888247Bao X, Pastan I, Bigner DD, Chandramohan V. EGFR/EGFRvIII-targeted immunotoxin therapy for the treatment of glioblastomas via convection-enhanced delivery. Receptors Clin Investig. 2016;3(4):e1430. doi: 10.14800/rci.1430.
PubMed 28286803Chandramohan V, Pegram CN, Piao H, Szafranski SE, Kuan CT, Pastan IH, Bigner DD. Production and quality control assessment of a GLP-grade immunotoxin, D2C7-(scdsFv)-PE38KDEL, for a phase I/II clinical trial. Appl Microbiol Biotechnol. 2017 Apr;101(7):2747-2766. doi: 10.1007/s00253-016-8063-x. Epub 2016 Dec 24.
PubMed 28013405