Phase 2a Study of CAN-2409 With Standard Radiation Therapy for Malignant Glioma

NCT00589875 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: BrTK02
• Study Type: interventional
• Target: 52
• Locations: 1 country
• Sites: 4

Brief Summary

The purpose of this study was to evaluate the safety and potential efficacy of CAN-2409 (also known / previously described as AdV-tk, GMCI) for malignant gliomas. The approach used an adenoviral vector (disabled virus) engineered to express the Herpes thymidine kinase gene (aglatimagene besadenovec, CAN-2409), followed by an antiherpetic prodrug, valacyclovir. CAN-2409 was injected into the resection bed after standard tumor surgery and valacyclovir pills were taken for 14 days. Standard radiation and chemotherapy were administered which have been shown to work cooperatively with CAN-2409 + prodrug to kill tumor cells. The hypothesis is that this combination therapy can be safely delivered and will lead to improvement in the clinical outcome for patients with newly diagnosed malignant gliomas, including glioblastoma multiforme (WHO grade IV) and anaplastic astrocytomas (WHO grade III).

Conditions

Malignant Glioma; Glioblastoma Multiforme; Anaplastic Astrocytoma; High Grade Glioma

Keywords

Immunotherapy; Cytotoxicity; Tumor vaccine; CAN-2409; AdV-tk; Candel Therapeutics, Inc.

Outcome Measures

Primary Outcomes (1)

• Number of Participants With Treatment Related Adverse Events

  2 months

Secondary Outcomes (1)

• Overall Survival

  5 years

Other Outcomes (2)

• Progression Free Survival

  24 months

• Functional Assessment of Cancer Therapy - Brain (FACT-Br)

  24 months

Study Arms (1)

Single arm

EXPERIMENTAL

This study is an extension of evaluation of the surgical resection arm, Arm B, from a phase Ib study in which dose escalation on arm B was completed.

Biological: CAN-2409; Drug: Valacyclovir; Drug: Temozolomide; Radiation: Radiation therapy

Interventions

CAN-2409 BIOLOGICAL

Single dose of 3x10e11 vector particles of CAN-2409 delivered to the tumor bed after resection on day 0.

Single arm

Valacyclovir DRUG

Single course of valacyclovir at dose of 2 grams orally three times per day for 14 days starting on day 1-3

Also known as: Valtrex

Single arm

Temozolomide DRUG

Concomitant TMZ will be administered orally once a day at a dose of 75 mg/m2 starting the next day after completing prodrug and continued for 6 weeks. Adjuvant TMZ will be administered days 1 to 5 of a 28-day cycle for 6 cycles with 150 mg/m2 administered for cycle 1, and 150 to 200 mg/m2 administered for cycles 2 to 6. Adjuvant treatment will start 1 month following completing RT.

Single arm

Radiation therapy RADIATION

Radiation will be administered to up-front patients as per standard of care for the patient. It will start 3-7 days after CAN-2409 injection, preferably closer to 3 days. It will consist of standard external field radiation, limited to the area of tumor and brain adjacent to tumor, fractionated at doses of 200cGy per day for approximately 6 weeks to a total of 5500-6000 cGy.

Single arm

Eligibility Criteria

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

You may qualify if:

• Patients must have presumed resectable or partially resectable malignant glioma based on clinical and radiologic evaluation (pathologic confirmation of malignant glioma must be made at the time of surgery if not previously determined). Patients who have previously received CAN-2409 + prodrug on this study may receive an additional CAN-2409 + prodrug course at recurrence if eligibility criteria are still met.
• Tumor must be accessible for injection and must not be located in the brainstem, midbrain, contained within the ventricular system, or located in an infratentorial location.
• Upfront patients must be planning to undergo standard radiation therapy.
• Patients must be 18 years of age or older.
• Performance status must be KPS ≥70.
• Patients must have SGOT (AST) \< 3x upper limit of normal.
• Patients must have serum creatinine \< 2mg/dl and calculated creatinine clearance \>10ml/min.
• Patients must have platelets \> 100,000/mm3 and WBC \> 3000/mm3.
• Patients of reproductive age must agree to use a medically accepted form of birth control while on the study.
• Patients must give study specific informed consent prior to enrollment. For re-administration, patients must be re-consented.
• Patients must be able to tolerate MRI scan procedure

You may not qualify if:

• Active liver disease including cirrhosis or hepatitis
• Patients on immunosuppressive drugs (with exception of corticosteroid)
• Known HIV+ patients.
• Patients with acute infections (viral, bacterial or fungal infections requiring therapy).
• Pregnant or breast feeding patients. Female patients of childbearing age must have negative serum or urine pregnancy test within 1 week of beginning therapy.
• Evidence of metastatic disease or other malignancy (except squamous or basal cell skin cancers).
• Other serious co-morbid illness or compromised organ function.
• Patients may not receive chemotherapy until valacyclovir is completed and may not receive other investigational anti-tumor agents within 30 days prior to study entry or during active participation in the study (defined as from CAN-2409 injection until tumor progression).

Sponsors & Collaborators

• Candel Therapeutics, Inc.: lead

Study Sites (4)

City of Hope Medical Center

Duarte, California, 91010, United States

Location

The University of Chicago

Chicago, Illinois, 60637, United States

Location

The Ohio State University Medical Center, Dept. Neurological Surgery

Columbus, Ohio, 43210, United States

Location

The Methodist Hospital Neurological Institute

Houston, Texas, 77030, United States

Location

Related Publications (1)

• Wheeler LA, Manzanera AG, Bell SD, Cavaliere R, McGregor JM, Grecula JC, Newton HB, Lo SS, Badie B, Portnow J, Teh BS, Trask TW, Baskin DS, New PZ, Aguilar LK, Aguilar-Cordova E, Chiocca EA. Phase II multicenter study of gene-mediated cytotoxic immunotherapy as adjuvant to surgical resection for newly diagnosed malignant glioma. Neuro Oncol. 2016 Aug;18(8):1137-45. doi: 10.1093/neuonc/now002. Epub 2016 Feb 2.

  PMID: 26843484 RESULT

Related Links

• Phase II multicenter study of gene-mediated cytotoxic immunotherapy as adjuvant to surgical resection for newly diagnosed malignant glioma

MeSH Terms

Conditions

Glioma; Glioblastoma; Astrocytoma

Interventions

Valacyclovir; Temozolomide; Radiotherapy

Condition Hierarchy (Ancestors)

Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Intervention Hierarchy (Ancestors)

Acyclovir; Guanine; Hypoxanthines; Purinones; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Dacarbazine; Triazenes; Organic Chemicals; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Therapeutics

Results Point of Contact

• Title: Garrett Nichols (CMO)
• Organization: Candel Therapeutics

Gnichols@candeltx.com

617-916-5445

Study Officials

• E. Antonio Chiocca, MD, PhD

  Ohio State University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 27, 2007
• First Posted: January 10, 2008
• Study Start: March 1, 2007
• Primary Completion: December 1, 2015
• Study Completion: August 1, 2016
• Last Updated: April 3, 2024
• Results First Posted: April 3, 2024

Record last verified: 2024-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (4)