Neoplasms

All Conditions

Rare Diseases

Glioma

Glioblastoma

Astrocytoma

Neoplasms, Neuroepithelial

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms by Histologic Type

Neoplasms, Glandular and Epithelial

Neoplasms, Nerve Tissue

Anaplastic Astrocytoma

Neuroepithelioma

All Drugs and Chemicals

Anti-Infective Agents

Vaccines

Immunomodulating Agents

Valacyclovir

Antiviral Agents

Arm A for unresectable malignant glioma was closed due to poor accrual.

Arm B for resectable malignant glioma completed the Phase I accrual and long term follow up continues. A follow on study at dose level 3 was opened as a Phase 2a study (see BrTK02).

Three different dosing levels of AdV-tk (3x10e10, 1x10e11, 3X10e11) were evaluated. A single injection of AdV-tk at the assigned dose level was administered, followed by 14 days of the oral prodrug valacyclovir. Patients then received standard of care radiation therapy and chemotherapy.

AdV-tk

The oral prodrug valacyclovir was given beginning 1-3 days following the AdV-tk. Valacyclovir tablets were taken three times a day for a total of 14 days.

E. Antonio Chiocca, MD, PhD

This phase I study evaluated a Gene Mediated Cytotoxic Immunotherapy approach for malignant gliomas, including glioblastoma multiforme and anaplastic astrocytoma. The purpose of this study was to assess the safety and feasibility of delivering an experimental approach called GliAtak which uses AdV-tk, an adenoviral vector containing the Herpes Simplex thymidine kinase gene, plus an oral anti-herpetic prodrug, valacyclovir, in combination with standard of care radiation.

This study was designed to include patients with newly diagnosed unresectable (Arm A) and resectable (Arm B) malignant glioma. Three dose levels of AdV-tk were evaluated with a fixed dose level of valacyclovir prodrug. AdV-tk was delivered to tumor cells by stereotactic injection into the tumor at the time of biopsy (Arm A) or injection into the tumor bed following resection (Arm B). Oral valacyclovir began 1-3 days after the AdV-tk injection and continued for 14 days. Standard radiation therapy began 3-7 days following the AdV-tk injection to maximize synergy with radiation. Standard temozolomide could be administered after completion of valacyclovir.

Phase 1b Study of AdV-tk + Valacyclovir Combined With Radiation Therapy for Malignant Gliomas

A Phase 1b Study of AdV-tk + Valacyclovir Gene Therapy in Combination With Standard Radiation Therapy for Malignant Gliomas

Candel Therapeutics, Inc.

Antineoplastic Agents

Dermatologic Agents

Temozolomide

Coal Tar

Antineoplastic Agents, Alkylating

Alkylating Agents

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.

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

CAN-2409

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

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.

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.

Radiation therapy

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).

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.

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

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

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.

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

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

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.

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.

Single Arm

9 patients were withdrawn from the study prior to receiving treatment due to pathology inconsistent with malignant glioma.

Age, Categorical

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

All patient who initated experimental treatment in the study

Garrett Nichols (CMO)

Number of Participants With Treatment Related Adverse Events

Overall Survival

Progression Free Survival

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

Enrollment to Treatment Initiation

Treatment Initiation to Completion

Skin and Connective Tissue Diseases

Symptoms and General Pathology

Breast Neoplasms

Neoplasm Metastasis

Breast Diseases

Skin Diseases

Central Nervous System Depressants

Anesthetics

Cryotherapy treatment administered by an interventional radiologist: the cryotherapy needle is placed under local anesthesia, ultrasound monitoring in real time. A complete cryotherapy cycle is performed with: freezing until the entire tumor is frozen as judged by ultrasound, then thawing for the same duration and refreezing according to the same principle.

Cryotherapy treatment

Julien Frandon

Anissa Megzari

Jean-Paul Beregi

Nadine Houede

Frédéric Fiteni

Cryotherapy is a cold ablation technique used in many tumor locations. The destruction of tissues by cryoablation preserves proteins and in particular anti-tumor antigens, which could induce the stimulation of an immune response. Compared to other interventional radiology techniques, cryotherapy induces a higher immunogenic response. Studies describe complex responses with elevated levels of activating NK cells, circulating and anti-tumor T cells, and pro-inflammatory and NF-KB dependent cytokines.

In breast cancer, whether or not an immune response is triggered depends on the type of cryoablation used. Indeed, high intensity cryoablation (rapid freezing in one cycle of the entire tumor volume) seems to induce a tumor-specific immunodestructive response, whereas low frequency cryoablation (several small repetitive cycles until a sufficient volume of ice is obtained) does not induce an immunogenic response and can even induce an immunoregulation with immunotolerance of the tumor cells The University Hospital of Nîmes has recently acquired a new liquid nitrogen cryotherapy technique, more powerful than the one classically performed with Argon. This technique is used for palliative and analgesic purposes in patients with metastatic breast cancer presenting painful subcutaneous metastases. The aim of this study is to evaluate in these patients the changes in the tumor microenvironment and the immune response potentially induced by this very high intensity cryotherapy.

The study investigators hypothesize that locoregional treatment with liquid nitrogen cryotherapy of subcutaneous breast cancer metastases will allow a systemic response through the induction of an immune response. A better understanding of the type of immune response induced will allow the development of combined therapeutic strategies with curative and not only palliative and analgesic aims.

Evaluation of Changes in the Immunological Microenvironment Surrounding Subcutaneous Breast Cancer Metastases After Liquid Nitrogen Cryotherapy

Evaluation of Changes in the Immunological Microenvironment Surrounding Subcutaneous Breast Cancer Metastases After Liquid Nitrogen Cryotherapy: Descriptive Pilot Study.

Cytometry by Time Of Flight (CyTOF®) mass cytometry analysis of biopsy samples to identify lymphocyte and macrophage populations and anti-tumor markers

Scoring of complications and adverse events according to Common Terminology Criteria for Adverse Events (CTCAE) criteria

Brief Pain Inventory (BPI): score from 0-120

European Organisation for Research and Treatment of Cancer - C30 (EORTC QLQ-C30). This questionnaire is composed of 30 items grouped into 15 scales. A good quality of life is associated with a high score for the functional scales and a low score for the symptom scales

Centre Hospitalier Universitaire de Nīmes

Digestive System Diseases

Gland and Hormone Related Diseases

Adenocarcinoma

Pancreatic Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Endocrine Gland Neoplasms

Gastrointestinal Diseases

Pancreatic Diseases

Endocrine System Diseases

Pancreatic Cancer

Gastrointestinal Agents

Pancrelipase

Pancreatin

Arm A is for resectable tumors. The first AdV-tk course is given prior to surgery by CT or EUS guided injection into the tumor followed by 14 days of valacyclovir. The second AdV-tk injection is into the tumor bed at the time of surgery again followed by 14 days of valacyclovir.

Arm B is for locally advanced tumors for which chemoradiation is the planned standard of care treatment. AdV-tk is delivered by CT or EUS guided injection into the tumor. The first AdV-tk injection is given prior to starting chemoradiation and the second in week 3 of chemoradiation. Both injections are followed by 14 days of valacyclovir.

Enrollment has been completed for Arm B.

Four dose levels of AdV-tk with a fixed dose level of valacyclovir are evaluated independently in the two arms of the study due to differences in the concomitant standard of care treatments. The first AdV-tk course is given prior to surgery or radiation by CT or EUS guided injection into the tumor followed by 14 days of valacyclovir. The second AdV-tk injection is into the tumor bed at the time of surgery in Arm A or same as the first injection in Arm B again followed by 14 days of valacyclovir. The AdV-tk dose levels are: Level 1= 3x10e10 vector particles (vp), Level 2= 1x10e11 vp, Level 3= 3x10e11 vp, Level 4= 1x10e12 vp

Valacyclovir caplets at a dose of 2 grams orally three times per day is administered for 14 days starting 1-3 days after each of the two AdV-tk injections in both arms.

Mark Bloomston, MD

The purpose of this Phase 1 study is to evaluate the safety and potential efficacy of Gene Mediated Cytotoxic Immunotherapy for pancreatic cancer. The approach uses an adenoviral vector (disabled virus) engineered to express the Herpes thymidine kinase gene (AdV-tk), followed by an antiherpetic prodrug, valacyclovir.

The AdV-tk vector is injected into the tumor or tumor bed at the time of biopsy or standard tumor surgery after which valacyclovir pills are taken for 14 days. Two courses of AdV-tk, each followed by valacyclovir, are given as adjuvant to standard of care therapies (surgery and/or chemoradiation) which have been shown to work cooperatively with AdV-tk to kill tumor cells. Arm A is for resectable tumors in which the first course is given prior to surgery and the second is at the time of surgery. Arm B is for locally advanced disease in which both AdV-tk injections are administered by needle injection into the tumor before and during chemoradiation. The hypothesis is that this combination therapy can be safely delivered and will lead to improvement in the clinical outcome for patients with pancreatic cancer.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Phase 1b Study of AdV-tk + Valacyclovir Combined With Radiation Therapy for Malignant Gliomas	NCT00751270	Malignant Gliom... Glioblastoma Mu... Anaplastic Astr...	AdV-tk Valacyclovir	18 Years -	Candel Therapeutics, Inc.
Phase 2a Study of CAN-2409 With Standard Radiation Therapy for Malignant Glioma	NCT00589875	Malignant Gliom... Glioblastoma Mu... Anaplastic Astr... High Grade Glio...	CAN-2409 Valacyclovir Temozolomide Radiation thera...	18 Years -	Candel Therapeutics, Inc.
Phase 1b Study of AdV-tk + Valacyclovir Combined With Radiation Therapy for Malignant Gliomas	NCT00751270	Malignant Gliom... Glioblastoma Mu... Anaplastic Astr...	AdV-tk Valacyclovir	18 Years -	Candel Therapeutics, Inc.
Phase 1b Study of AdV-tk + Valacyclovir Combined With Radiation Therapy for Malignant Gliomas	NCT00751270	Malignant Gliom... Glioblastoma Mu... Anaplastic Astr...	AdV-tk Valacyclovir	18 Years -	Candel Therapeutics, Inc.
Phase 2a Study of CAN-2409 With Standard Radiation Therapy for Malignant Glioma	NCT00589875	Malignant Gliom... Glioblastoma Mu... Anaplastic Astr... High Grade Glio...	CAN-2409 Valacyclovir Temozolomide Radiation thera...	18 Years -	Candel Therapeutics, Inc.
Evaluation of Changes in the Immunological Microenvironment Surrounding Subcutaneous Breast Cancer Metastases After Liquid Nitrogen Cryotherapy	NCT05825547	Breast Cancer	Cryotherapy tre...	18 Years - 95 Years	Centre Hospitalier Universitaire de Nīmes
AdV-tk Therapy With Surgery and Chemoradiation for Pancreas Cancer (PaTK01)	NCT00638612	Pancreatic Aden... Pancreatic Canc...	AdV-tk Valacyclovir	18 Years -	Candel Therapeutics, Inc.

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