Phase 2a Study of CAN-2409 With Standard Radiation Therapy for Malignant Glioma (BrTK02)

March 7, 2024 updated by: Candel Therapeutics, Inc.

A Phase IIa Study of AdV-tk + Valacyclovir Gene Therapy in Combination With Standard Radiation Therapy for Malignant Gliomas

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).

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Patients had resectable or partially resectable malignant glioma and received injection of CAN-2409 into remaining tumor or tumor bed after resection. Pathologic confirmation of malignant glioma must be made prior to CAN-2409 injection; if this was not possible, the injection was not performed and the subject was no longer eligible for the study. The oral prodrug, valacyclovir, started 1-3 days after CAN-2409 injection and continued for 14 days. Standard radiotherapy began on average 7 days after CAN-2409 injection for the up-front course. Patients received temozolomide as per standard of care after completion of prodrug.

Study Type

Interventional

Enrollment (Actual)

52

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • California
      • Duarte, California, United States, 91010
        • City of Hope Medical Center
    • Illinois
      • Chicago, Illinois, United States, 60637
        • The University Of Chicago
    • Ohio
      • Columbus, Ohio, United States, 43210
        • The Ohio State University Medical Center, Dept. Neurological Surgery
    • Texas
      • Houston, Texas, United States, 77030
        • The Methodist Hospital Neurological Institute

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • 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).

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Single arm
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.
Drug: Valacyclovir
Single course of valacyclovir at dose of 2 grams orally three times per day for 14 days starting on day 1-3
Other Names:
  • Valtrex
Biological: CAN-2409
Single dose of 3x10e11 vector particles of CAN-2409 delivered to the tumor bed after resection on day 0.
Radiation: Radiation therapy
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.
Drug: Temozolomide
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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Number of Participants With Treatment Related Adverse Events
Time Frame: 2 months
2 months

Secondary Outcome Measures

Outcome Measure
Time Frame
Overall Survival
Time Frame: 5 years
5 years

Other Outcome Measures

Outcome Measure
Time Frame
Progression Free Survival
Time Frame: 24 months
24 months
Functional Assessment of Cancer Therapy - Brain (FACT-Br)
Time Frame: 24 months
24 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Candel Therapeutics, Inc.

Investigators

  • Principal Investigator: E. Antonio Chiocca, MD, PhD, Ohio State University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

March 1, 2007

Primary Completion (Actual)

December 1, 2015

Study Completion (Actual)

August 1, 2016

Study Registration Dates

First Submitted

December 27, 2007

First Submitted That Met QC Criteria

December 27, 2007

First Posted (Estimated)

January 10, 2008

Study Record Updates

Last Update Posted (Actual)

April 3, 2024

Last Update Submitted That Met QC Criteria

March 7, 2024

Last Verified

March 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • BrTK02

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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