RECRUITING

Phase 1 Trial of D2C7-IT in Combination With 2141-V11 for Recurrent Malignant Glioma

Conditions

Glioma, Malignant D2C7 D2C7-IT Glioblastoma Glioma 2141-V11 Pro00104852 Duke Rockefeller CD40 epidermal growth factor receptor (EGFR)EGFR Landi

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

This is a phase 1 study of an anti-CD40 monoclonal antibody (2141-V11) in combination with D2C7-IT for patients with recurrent World Health Organization (WHO) grade III or IV malignant glioma at the Preston Robert Tisch Brain Tumor Center (PRTBTC) at Duke.

Official Title

A Phase 1 Trial of D2C7-IT in Combination With an Fc-engineered Anti-CD40 Monoclonal Antibody (2141-V11) Administered Intratumorally Via Convection-Enhanced Delivery for Adult Patients With Recurrent Malignant Glioma

Quick Facts

Study Start:2021-07-09

Study Completion:2025-12

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT04547777

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:18 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion Criteria
* Histopathologically confirmed recurrent supratentorial WHO grade III or IV malignant glioma (high grade glioma with molecular features of glioblastoma will be eligible under 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 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. * 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 prior to biopsy * Creatinine ≤ 1.5 x normal range prior to biopsy * Total bilirubin ≤ 1.5 x upper limit of normal (ULN) prior to biopsy (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) * Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) ≤ 2.5 x ULN * 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. * 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	* 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 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 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 * 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 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 have received treatment with tumor treating fields (e.g., Optune) ≤ 1 week prior to starting the study drug * 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 (Please note: For patients under 65 years old, standard radiation therapy is typically at least 59 Gy in 30 fractions over 6 weeks. For patients 65 years or older, standard RT is often reduced to a minimum 40 Gy in 15v fractions over 3 weeks.) 1. If the O\^6-methylguanine-DNA methyltransferase (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 active autoimmune disease requiring systemic immunomodulatory treatment within the past 3 months

Inclusion Criteria

Exclusion Criteria

* Histopathologically confirmed recurrent supratentorial WHO grade III or IV malignant glioma (high grade glioma with molecular features of glioblastoma will be eligible under 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 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.
* 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 prior to biopsy
* Creatinine ≤ 1.5 x normal range prior to biopsy
* Total bilirubin ≤ 1.5 x upper limit of normal (ULN) prior to biopsy (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)
* Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) ≤ 2.5 x ULN
* 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.
* 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

* 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 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 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
* 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 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 have received treatment with tumor treating fields (e.g., Optune) ≤ 1 week prior to starting the study drug
* 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 (Please note: For patients under 65 years old, standard radiation therapy is typically at least 59 Gy in 30 fractions over 6 weeks. For patients 65 years or older, standard RT is often reduced to a minimum 40 Gy in 15v fractions over 3 weeks.)
1. If the O\^6-methylguanine-DNA methyltransferase (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 active autoimmune disease requiring systemic immunomodulatory treatment within the past 3 months

Contacts and Locations

Study Contact

Annick Desjardins, MD. FRCPC

CONTACT

919-684-5301

dukebrain1@dm.duke.edu

Stevie Threatt

CONTACT

919-684-5301

dukebrain1@dm.duke.edu

Principal Investigator

Annick Desjardins, MD,FRCPC

PRINCIPAL_INVESTIGATOR

Duke University

Study Locations (Sites)

Duke University Medical Center

Durham, North Carolina, 27710

United States

Collaborators and Investigators

Sponsor: Darell Bigner

Annick Desjardins, MD,FRCPC, PRINCIPAL_INVESTIGATOR, Duke University

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2021-07-09

Study Completion Date2025-12

Study Record Updates

Study Start Date2021-07-09

Study Completion Date2025-12

Terms related to this study

Keywords Provided by Researchers

D2C7
D2C7-IT
Glioblastoma
Glioma
2141-V11
Pro00104852
Duke
Rockefeller
CD40
epidermal growth factor receptor (EGFR)
EGFR
Landi

Additional Relevant MeSH Terms

Glioma, Malignant