Pilot Immunotherapy Trial for Recurrent Malignant Gliomas
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.
|Malignant Glioma of Brain||Drug: IGF-1R/AS ODN Device: biodiffusion chamber||Phase 1|
|Study Design:||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|
- 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. ]
- 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) ]
|Study Start Date:||January 2012|
|Study Completion Date:||June 2013|
|Primary Completion Date:||June 2013 (Final data collection date for primary outcome measure)|
|Placebo Comparator: a||
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: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.
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Please refer to this study by its ClinicalTrials.gov identifier: NCT01550523
|United States, Pennsylvania|
|Thomas Jefferson University Hospital; Jefferson Hospital for Neurosciences|
|Philadelphia, Pennsylvania, United States, 19107|
|Principal Investigator:||David W Andrews, MD||Thomas Jefferson University|