DNX-2401 (Formerly Known as Delta-24-RGD-4C) for Recurrent Malignant Gliomas

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
DNAtrix, Inc.
ClinicalTrials.gov Identifier:
NCT00805376
First received: December 8, 2008
Last updated: June 12, 2014
Last verified: June 2014
  Purpose

The goal of this clinical research study is to find the highest tolerable dose of DNX-2401 that can be injected directly into brain tumors and into the surrounding brain tissue where tumor cells can multiply. A second goal is to study how the new drug DNX-2401 affects brain tumor cells and the body in general.


Condition Intervention Phase
Brain Cancer
Central Nervous System Diseases
Drug: DNX-2401
Procedure: Tumor Removal
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase I Trial of Conditionally Replication-Competent Adenovirus (DNX-2401, Formerly Known as Delta-24-RGD-4C) for Recurrent Malignant Gliomas

Resource links provided by NLM:


Further study details as provided by DNAtrix, Inc.:

Primary Outcome Measures:
  • Maximum Tolerated Dose (MTD) DNX-2401 [ Time Frame: Assessed during 14 day waiting period between doses (every 28 days). ] [ Designated as safety issue: Yes ]
    Each cohort of three subjects each sequentially assigned to escalating doses of DNX-2401, with acceptable grade of neurotoxicity Common Toxicity Criteria (CTC) < grade 3, related to the study drug, and according to standard Gehan phase I dose-escalating criteria for toxicity.


Estimated Enrollment: 96
Study Start Date: December 2008
Estimated Primary Completion Date: December 2021 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Group A: DNX-2401
Surgical procedure precisely injects DNX-2401 through a catheter (small tube) into brain tumor.
Drug: DNX-2401
Surgical procedure precisely injects DNX-2401 through a catheter (small tube) into brain tumor.
Other Name: Delta-24-RGD-4C
Experimental: Group B: DNX-2401 + Surgery
DNX-2401 injection + Tumor removal
Drug: DNX-2401
Surgical procedure precisely injects DNX-2401 through a catheter (small tube) into brain tumor.
Other Name: Delta-24-RGD-4C
Procedure: Tumor Removal
Surgical Tumor Resection
Other Name: Craniotomy

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Patients with histologically proven recurrent malignant primary glioma will be eligible. Glioma type will be restricted to: GBM, gliosarcoma (GS), anaplastic gliomas [anaplastic astrocytoma (AA), anaplastic oligodendroglioma (AO), anaplastic infiltrating glioma (AIG), mixed anaplastic glioma (MAG), anaplastic ependymoma]
  2. Patients must show unequivocal evidence for tumor recurrence or progression by MRI scan within 15 days prior to Day 0/Baseline procedure after failing prior surgical resection, biopsy, chemotherapy or radiation
  3. For patients entered in Group A (see Treatment Plan) tumors must be accessible for stereotactic injection. Tumors must be between 1.0 - 5.0 cm in diameter
  4. For patients entered in Group B (see Treatment Plan) tumors must be surgically resectable, and surgical resection must be indicated at the time of baseline evaluation. Tumors must be >1.0 cm in diameter.
  5. Patients will consent to have a biopsy taken at the time of the stereotactic injection to confirm the presence of malignant glioma (based on frozen section) before injection of DNX-2401
  6. For each patient there must be a consensus between the physician investigators in this study that injection will not deliver DNX-2401 into the ventricular system. Patients must have a stable steroid regimen for at least 1 week prior to DNX-2401 administration
  7. Patients may or may not have had prior chemotherapy
  8. Patients must be willing and able to give informed consent
  9. Age > /= 18 years
  10. Patients must have a Karnofsky performance status greater than or equal to 70
  11. Patients must have recovered from the toxic effects of prior therapy (i.e., CTC grade 1 or less). For example, they must be at least two weeks after vincristine, 6 weeks after nitrosoureas, and 3 weeks after procarbazine or temozolomide administration
  12. Patients must have adequate bone marrow function (absolute granulocyte count > 1,500 and platelet count of > 100,000), adequate liver function (SGPT and alkaline phosphatase < 2 times institutional normals and bilirubin <1.5 mg%), and adequate renal function (BUN or creatinine <1.5 times institutional normal) prior to starting therapy
  13. This study was designed to include women and minorities, but was not designed to measure differences of intervention effects. Males and females will be recruited with no preference to gender
  14. No exclusion to this study will be based on race. Minorities will actively be recruited to participate. The malignant glioma patient population treated at MDACC over the past year is as follows: American Indian or Alaskan Native - 0, Asian or Pacific Islander - <2%, Black, not of Hispanic Origin - 3%, Hispanic - 6%, White, not of Hispanic Origin - 88%, Other or Unknown - 2%, Total - 100%

Exclusion Criteria:

  1. Any radiotherapy within 4 weeks prior to date of DNX-2401 administration.
  2. Active uncontrolled infection or severe intercurrent medical conditions. All patients must be afebrile at baseline (i.e., < 38.0 Celsius [C])
  3. Evidence of bleeding diathesis or use of anticoagulant medication or any medication that may increase the risk of bleeding that cannot be stopped prior to surgery. If the medication can be discontinued , based on the clinical judgment of the surgeon, prior to DNX-2401 injection then patient may be eligible.
  4. History or current diagnosis of any medical or psychological condition that in the Investigator's opinion, might interfere with the subject's ability to participate or inability to obtain informed consent because of psychiatric or complicating medical problems
  5. Female who is pregnant and/or nursing. Because of the potential risk of a recombinant virus containing a gene involved in cellular growth regulation and differentiation which could potentially affect a developing fetus or growing infant, females who are pregnant, at risk of pregnancy, or breast feeding a baby during the study period are excluded
  6. Tumor position that, in the Investigator's opinion, would pose the risk of penetration of the cerebral ventricular system during injection with study drug. If, during the DNX-2401injection procedure, penetration of the ventricular system is suspected or confirmed, DNX-2401 administration will be aborted
  7. Immunocompromised subjects, subjects with autoimmune conditions, active hepatitis (B or C) or HIV seropositivity
  8. Patients with Li-Fraumeni Syndrome or with a known germ line deficit in the retinoblastoma gene or its related pathways
  9. Multiple intracranial malignant glioma lesions at the time of recurrence. Multiple enhancing areas within a single tumor will not be considered multiple glioma lesions
  10. Tumor involvement which would require ventricular, brainstem or posterior fossa injection or access through a ventricle in order to deliver the virus
  11. Tumor involving the subependyma or suspected cerebrospinal fluid (CSF) dissemination
  12. Documented extracranial metastasis
  13. Biologic/immunotherapy (e.g., IL-2, IL-12, interferon) within 4 weeks of DNX-2401 administration
  14. Concurrent chemotherapy, radiation or biological therapy
  15. Any contraindication for undergoing MRI such as: individuals with pacemakers, epicardial pacer wires, infusion pumps, surgical and/or aneurysm clips, shrapnel, metal prosthesis, implants with potential magnetic properties, metallic bodies in the eyes, etc.
  16. White blood cell (WBC) < 2.5 x 103/mm3, absolute neutrophil count (ANC) < 1.5 x 103/mm3, platelet < 100,000/mm3, hemoglobin (Hgb) < 10.0 gm/dL, prothrombin time/international normalized ratio (PT/INR) or partial thromboplastin time (PTT) > 1.8 x control
  17. Grade 4 hematological toxicity
  18. Serum creatinine > 1.5 mg/dL
  19. Liver transaminases (aspartate aminotransferase [AST] and/or alanine aminotransferase [ALT]) or total bilirubin > 2x the upper limits of normal
  20. Vaccinations of any kind within 30 days prior to Delta-24-RGD-4C administration
  21. Current diagnosis of other cancer except curative cervical cancer in situ, basal or squamous cell carcinoma of the skin. Patients with a history of another cancer, but who are cancer free for a minimum of three years remain eligible
  22. History of encephalitis, multiple sclerosis, other CNS infection or primary CNS disease that would interfere with subject evaluation
  23. Patients with history of prior gene transfer therapy or prior therapy with cytolytic virus of any type, especially DNX-2401
  24. Males or females who refuse to use a double-barrier form of birth control during the study and for up to 6 months after injection with DNX-2401
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00805376

Locations
United States, Texas
UT MD Anderson Cancer Center
Houston, Texas, United States, 77030
Sponsors and Collaborators
DNAtrix, Inc.
Investigators
Principal Investigator: Frederick F. Lang, MD, BS UT MD Anderson Cancer Center
  More Information

Additional Information:
No publications provided

Responsible Party: DNAtrix, Inc.
ClinicalTrials.gov Identifier: NCT00805376     History of Changes
Other Study ID Numbers: ID01-310
Study First Received: December 8, 2008
Last Updated: June 12, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by DNAtrix, Inc.:
Brain
Brain Cancer
Central Nervous System Diseases
CNS
Conditionally Replication-Competent Adenovirus
Delta-24-RGD
DNX-2401
Recurrent Malignant Gliomas
malignant brain tumor

Additional relevant MeSH terms:
Brain Neoplasms
Central Nervous System Diseases
Glioma
Nervous System Diseases
Central Nervous System Neoplasms
Nervous System Neoplasms
Neoplasms by Site
Neoplasms
Brain Diseases
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue

ClinicalTrials.gov processed this record on July 20, 2014