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Pilot Immunotherapy Trial for Recurrent Malignant Gliomas

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT01550523
Recruitment Status : Completed
First Posted : March 12, 2012
Last Update Posted : June 20, 2018
Information provided by (Responsible Party):
Thomas Jefferson University ( Sidney Kimmel Cancer Center at Thomas Jefferson University )

Brief Summary:

This human Phase I trial involves taking the patient's own tumor cells during surgical craniotomy, treating them with an investigational new drug (an antisense molecule) designed to shut down a targeted surface receptor protein, and re-implanting the cells, now encapsulated in small diffusion chambers the size of a dime in the patient's abdomen within 24 hours after the surgery. Loss of the surface receptor causes the tumor cells to die in a process called apoptosis. As the tumor cells die, they release small particles called exosomes, each full of tumor antigens. It is believed that these exosomes as well as the presence of the antisense molecule work together to activate the immune system against the tumor as they slowly diffuse out of the chamber. This combination product therefore serves as a slow-release antigen depot. Immune cells are immediately available for activation outside of the chamber because a wound was created to implant these tumor cells and a foreign body (the chamber) is present in the wound. The wound and the chamber fortify the initial immune response which eventually leads to the activation of immune system T cells that attack and eliminate the tumor. By training the immune system to recognize the tumor, the patient is also protected through immune surveillance from later tumor growth should the tumor recur. Compared to the other immunotherapy strategies, this treatment marshalls the native immune system (specifically the antigen presenting cells, or dendritic cells) rather than engineering the differentiation of these immune cells and re-injecting them. Compared to traditional treatment alternatives for tumor recurrence, including a boost of further radiation and more chemotherapy, this treatment represents potentially greater benefit with fewer risks.

This combination product serves as a therapeutic vaccine with an acceptable safety profile, which activates an anti-tumor adaptive immune response resulting in radiographic tumor regression.

Condition or disease Intervention/treatment Phase
Malignant Glioma of Brain Drug: IGF-1R/AS ODN Device: biodiffusion chamber Phase 1

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 13 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase 1 Study in Humans Evaluating the Safety of Rectus Sheath Implantation of Diffusion Chambers Encapsulating Autologous Malignant Glioma Cells Treated With Insulin-Like Growth Factor Receptor-1 Antisense Oligodeoxynucleotide in 12 Patients With Recurrent Malignant Glioma
Actual Study Start Date : February 9, 2012
Actual Primary Completion Date : June 25, 2013
Actual Study Completion Date : June 25, 2013

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
Experimental: 18-mer oligodeoxynucleotide Drug: IGF-1R/AS ODN
Patients will receive approximately 10 to 20 million IGF-1R/AS ODN treated tumor cells, encapsulated in diffusion chambers (maximum of 10), and re-implanted in the patient's abdomen within 24 hours after the surgery for a 24 hour period.
Other Names:
  • Nobel Sequence
  • Antisense
  • AS ODN

Device: biodiffusion chamber
The biodiffusion chamber is a simple construct comprised of two Lucite rings sealed on either side with a 0.1u mesh filter (Durapore, the Millipore Corporation). Autologous tumor cells pretreated with the IGF-1R AS ODN and resuspended with 2ug of exogenous IGF-1R AS ODN are added to the chamber. Implantation of the chambers (maximum 10 chambers) occurs 24 hours post surgery for 24 hours.

Primary Outcome Measures :
  1. To establish the safety profile of a combination product with an optimized Good Manufacturing Practices AS ODN in the treatment of patients with recurrent malignant glioma with concomitant assessment of any therapeutic impact. [ Time Frame: Continuous throughout 24 month study participation. ]

Secondary Outcome Measures :
  1. MRI based radiographic responses to treatment [ Time Frame: <3 days prior to craniotomy, Day 28 post craniotomy, Day 56 post craniotomy, then every 3 months until 24 months (study completion at 24 months) ]

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Failure after previous standard of care initial treatment of glioblastoma multiforme.
  • Documentation by MRI of an interval increase in nodular gadolinium enhancement consistent with recurrent malignant glioma suitable for therapeutic re-resection.
  • Previous pathological diagnosis of WHO Grade IV glioma.
  • All previous treatment interventions are acceptable.
  • Patients must have an ECOG (Eastern Cooperative Oncology Group) performance status of 0, 1, or 2 or a KPS (Karnofsky Performance Score) of at least 60.
  • Patients must be 18 years of age or older.
  • Patients must sign an approved informed consent.
  • Hemodynamically stable, consistent with Standard of Care values for patients undergoing elective tumor resection.

Exclusion Criteria:

  • Females who are pregnant, nursing, or not inclined to use adequate contraceptive methods if necessary to prevent pregnancy during the study.
  • An active second primary malignancy with the exception of basal cell or squamous cell skin carcinoma.
  • Major concomitant medical illness inclusive of severe chronic obstructive pulmonary disease, symptomatic coronary artery disease, heart failure, recent major cerebrovascular accident, brittle diabetes, renal dialysis, end stage liver disease, or labile hypertension.
  • Patients who have a history of heparin-induced thrombocytopenia or hypersensitivity to heparin, enoxaparin, or pork products.
  • Patients with an abnormal INR (International Normalized Ratio of greater than 1.3), if repeatable and refractory to correction by routine methods.
  • Patients who have documented deep venous thrombosis

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01550523

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United States, Pennsylvania
Thomas Jefferson University Hospital; Jefferson Hospital for Neurosciences
Philadelphia, Pennsylvania, United States, 19107
Sponsors and Collaborators
Sidney Kimmel Cancer Center at Thomas Jefferson University
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Principal Investigator: David W Andrews, MD Thomas Jefferson University

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Responsible Party: Sidney Kimmel Cancer Center at Thomas Jefferson University
ClinicalTrials.gov Identifier: NCT01550523    
Other Study ID Numbers: 11G.532
First Posted: March 12, 2012    Key Record Dates
Last Update Posted: June 20, 2018
Last Verified: June 2018

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Thomas Jefferson University ( Sidney Kimmel Cancer Center at Thomas Jefferson University ):
Brain Tumor
Additional relevant MeSH terms:
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Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue