Pilot Immunotherapy Trial for Recurrent Malignant Gliomas

NCT01550523 | Completed Phase 1 DMC FDA Drug

• 2 other identifiers: 11G.532JT 1587
• Study Type: interventional
• Target: 13
• Locations: 1 country
• Sites: 1

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.

Conditions

Malignant Glioma of Brain

Keywords

Brain Tumor

Outcome Measures

Primary Outcomes (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.

  Continuous throughout 24 month study participation.

Secondary Outcomes (1)

• MRI based radiographic responses to treatment

  <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 Arms (1)

18-mer oligodeoxynucleotide

EXPERIMENTAL

Drug: IGF-1R/AS ODN; Device: biodiffusion chamber

Interventions

IGF-1R/AS ODN DRUG

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.

Also known as: Nobel Sequence, Antisense, AS ODN

18-mer oligodeoxynucleotide

biodiffusion chamber DEVICE

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.

18-mer oligodeoxynucleotide

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Sidney Kimmel Cancer Center at Thomas Jefferson University: lead

Study Sites (1)

Thomas Jefferson University Hospital; Jefferson Hospital for Neurosciences

Philadelphia, Pennsylvania, 19107, United States

Location

Related Publications (15)

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  PMID: 9389920 BACKGROUND

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  PMID: 19430892 BACKGROUND

• Carpentier A, Laigle-Donadey F, Zohar S, Capelle L, Behin A, Tibi A, Martin-Duverneuil N, Sanson M, Lacomblez L, Taillibert S, Puybasset L, Van Effenterre R, Delattre JY, Carpentier AF. Phase 1 trial of a CpG oligodeoxynucleotide for patients with recurrent glioblastoma. Neuro Oncol. 2006 Jan;8(1):60-6. doi: 10.1215/S1522851705000475.

  PMID: 16443949 BACKGROUND

• Chaput N, Schartz NE, Andre F, Taieb J, Novault S, Bonnaventure P, Aubert N, Bernard J, Lemonnier F, Merad M, Adema G, Adams M, Ferrantini M, Carpentier AF, Escudier B, Tursz T, Angevin E, Zitvogel L. Exosomes as potent cell-free peptide-based vaccine. II. Exosomes in CpG adjuvants efficiently prime naive Tc1 lymphocytes leading to tumor rejection. J Immunol. 2004 Feb 15;172(4):2137-46. doi: 10.4049/jimmunol.172.4.2137.

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• Cosaceanu D, Carapancea M, Alexandru O, Budiu R, Martinsson HS, Starborg M, Vrabete M, Kanter L, Lewensohn R, Dricu A. Comparison of three approaches for inhibiting insulin-like growth factor I receptor and their effects on NSCLC cell lines in vitro. Growth Factors. 2007 Feb;25(1):1-8. doi: 10.1080/08977190600702865.

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MeSH Terms

Conditions

Brain Neoplasms

Condition Hierarchy (Ancestors)

Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Neoplasms; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Study Officials

• David W Andrews, MD

  Thomas Jefferson University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 14, 2012
• First Posted: March 12, 2012
• Study Start: February 9, 2012
• Primary Completion: June 25, 2013
• Study Completion: June 25, 2013
• Last Updated: May 2, 2025

Record last verified: 2025-05

Locations

US (1)