Clinical Trials /

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

NCT04547777

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.

Related Conditions:
  • Malignant Glioma
Recruiting Status:

Not yet recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

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

Clinical Trial IDs

  • ORG STUDY ID: Pro00104852
  • NCT ID: NCT04547777

Conditions

  • Glioma, Malignant

Interventions

DrugSynonymsArms
D2C7-ITD2C7-IT + 2141-V11
2141-V11anti-CD40D2C7-IT + 2141-V11

Purpose

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.

Detailed Description

      Within this study, a maximum of 30 patients with recurrent WHO grade III and IV malignant
      glioma will receive D2C7-IT and 2141-V11 to determine the impact of the combination of
      D2C7-IT and 2141-V11 on safety. D2C7-IT and 2141-V11 will be delivered sequentially directly
      into the tumor by Convection Enhanced Delivery (CED) using an intracerebral catheter placed
      within the enhancing portion of the tumor. Based on a phase 1 study of D2C7-IT in adult
      patients with recurrent glioblastoma (GBM), the amount of D2C7-IT to be delivered will be
      6920 ng/mL (36 mL). 2141-V11 will be dose escalated during the study to determine the maximum
      tolerated dose (MTD) when used in combination with D2C7-IT.
    

Trial Arms

NameTypeDescriptionInterventions
D2C7-IT + 2141-V11ExperimentalSingle D2C7-IT intratumoral infusion (6920 ng/mL in 36 mL) over 72 hours followed by single 2141-V11 infusion (5 dose levels) over 7 hours
  • D2C7-IT
  • 2141-V11

Eligibility Criteria

        Inclusion 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

        Exclusion Criteria:

          -  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 (at least 59 Gy)

               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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Proportion of patients with dose-limiting toxicity (DLT) within each dose level
Time Frame:28 days after catheter removal
Safety Issue:
Description:DLTs are defined as any of the following events that are at least possibly, probably, or definitely attributable to study treatment (D2C7-IT or 2141-V11) during dose escalation: • Any Grade 3 or any Grade 4 toxicity that is not reversible within 2 weeks, including cerebral edema or worsening neurologic symptoms, or any life-threatening event, or treatment-related death, or any grade 2 or higher serious autoimmune toxicities

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Darell Bigner

Trial Keywords

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

Last Updated

September 8, 2020