Pilot Immunotherapy Trial for Recurrent Malignant Gliomas - Full Text View

Purpose

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

Study Type:	Interventional
Study Design:	Endpoint Classification: Safety Study Intervention Model: Single Group Assignment Masking: 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

Resource links provided by NLM:

MedlinePlus related topics: Cancer Diabetes Medicines

Drug Information available for: Insulin-like growth factor I Mecasermin rinfabate

U.S. FDA Resources

Further study details as provided by Thomas Jefferson University:

Primary Outcome Measures:

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. ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

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) ] [ Designated as safety issue: No ]

Estimated Enrollment:	12
Study Start Date:	January 2012
Estimated Study Completion Date:	March 2014
Estimated Primary Completion Date:	March 2014 (Final data collection date for primary outcome measure)

Intervention Details:

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

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.

Show Detailed Description

Eligibility

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

Criteria

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT01550523

Contacts

Contact: Meghan P Wakefield, RN	215-503-9110	meghan.wakefield@jefferson.edu
Contact: John Furlong, RN	215-955-7301	john.furlong@jefferson.edu

Locations

United States, Pennsylvania
Thomas Jefferson University Hospital; Jefferson Hospital for Neurosciences	Recruiting
Philadelphia, Pennsylvania, United States, 19107
Contact: Meghan P Wakefield, RN 215-503-9110 meghan.wakefield@jefferson.edu
Principal Investigator: David W Andrews, MD

Sponsors and Collaborators

Thomas Jefferson University

Investigators

Principal Investigator:

David W Andrews, MD

Thomas Jefferson University

More Information

Publications:

Andrews DW, Resnicoff M, Flanders AE, Kenyon L, Curtis M, Merli G, Baserga R, Iliakis G, Aiken RD. Results of a pilot study involving the use of an antisense oligodeoxynucleotide directed against the insulin-like growth factor type I receptor in malignant astrocytomas. J Clin Oncol. 2001 Apr 15;19(8):2189-200.

Responsible Party:	Thomas Jefferson University
ClinicalTrials.gov Identifier:	NCT01550523 History of Changes
Other Study ID Numbers:	DWA-11G.532
Study First Received:	February 14, 2012
Last Updated:	February 18, 2013
Health Authority:	United States: Food and Drug Administration

Keywords provided by Thomas Jefferson University:

Brain Tumor

Additional relevant MeSH terms:

Glioma
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal

Neoplasms by Histologic Type
Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue

ClinicalTrials.gov processed this record on June 17, 2013