Neoplasms

Digestive System Diseases

Gland and Hormone Related Diseases

All Conditions

Respiratory Tract (Lung and Bronchial) Diseases

Symptoms and General Pathology

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Rare Diseases

Pancreatic Neoplasms

Stomach Neoplasms

Sarcoma

Lung Neoplasms

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Urinary Bladder Neoplasms

Hypoxia

Pancreatic Cancer

Stomach Cancer

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Herbal and Botanical

All Drugs and Chemicals

Cola

Clostridium novyi-NT spores

Luis A Diaz, MD

This study will include a one time intravenous (IV) infusion of Clostridium novyi-NT (C. novyi-NT) spores to treat solid tumors which have not responded to standard therapy.

Investigators at the SKCCC have developed a bacterial strain (C. novyi-NT) that can infect tumors and destroy them, but does not grow in normal tissues. In animal experiments, a single intravenous injection of these bacteria can cause dramatic regression of many tumors, and the tumors do not recur in approximately (\~) 30% of the animals.

This is a phase I dose escalation study using a single dose of Clostridium novyi-NT spores in patients with treatment-refractory solid tumor malignancies. The overall objective of this study is to determine the safety and document any preliminary evidence of anti-tumor activity in this patient population.

One Time Injection of Bacteria to Treat Solid Tumors That Have Not Responded to Standard Therapy

Phase I Safety Study of Clostridium Novyi-NT Spores in Patients With Treatment-Refractory Solid Tumor Malignancies

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Behaviors and Mental Disorders

Recurrence

Glioblastoma

Disease Progression

Astrocytoma

Disease Attributes

Glioma

Neoplasms, Neuroepithelial

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms by Histologic Type

Neoplasms, Glandular and Epithelial

Neoplasms, Nerve Tissue

Quality of Life

Neuroepithelioma

Antineoplastic Agents

Temozolomide

Immunomodulating Agents

Lomustine

Antineoplastic Agents, Alkylating

Alkylating Agents

Best oncological treatment consisting of re-challenge temozolomide, re-irradiation, experimental therapy, or best supportive care

Re-resection

Re-irradiation with single dose, fractionated, or hypofractionated radiation of the recurrent tumor

Re-irradiation

Experimental phase I therapy with oncolytic virotherapy or immunotherapy (this list is not exhaustive)

Experimental therapy

Best supportive care, focused on alleviating symptoms

Best supportive care

Jasper Gerritsen, MD PhD

Arnaud Vincent, MD PhD

Mitchel Berger, MD PhD

Brian Nahed, MD PhD

Steven De Vleeschouwer, MD PhD

Christine Jungk, Dr. med.

Arthur Wagner, MD

Jasper Gerritsen, MD

Marike Broekman, MD PhD

Philippe Schucht, MD PhD

Previous evidence has indicated that resection for recurrent glioblastoma might benefit the prognosis of these patients in terms of overall survival. However, the demonstrated safety profile of this approach is contradictory in the literature and the specific benefits in distinct clinical and molecular patient subgroups remains ill-defined. The aim of this study, therefore, is to compare the effects of resection and best oncological treatment for recurrent glioblastoma as a whole and in clinically important subgroups.

This study is an international, multicenter, prospective observational cohort study. Recurrent glioblastoma patients will undergo tumor resection or best oncological treatment at a 1:1 ratio as decided by the tumor board. Primary endpoints are: 1) proportion of patients with NIHSS (National Institute of Health Stroke Scale) deterioration at 6 weeks after surgery and 2) overall survival. Secondary endpoints are: 1) progression-free survival (PFS), 2) NIHSS deterioration at 3 months and 6 months after surgery, 3) health-related quality of life (HRQoL) at 6 weeks, 3 months, and 6 months after surgery, and 4) frequency and severity of Serious Adverse Events (SAEs) in each arm. Estimated total duration of the study is 5 years. Patient inclusion is 4 years, follow-up is 1 year.

The study has been approved by the Medical Ethics Committee (METC Zuid-West Holland/Erasmus Medical Center; MEC-2020-0812). The results will be published in peer-reviewed academic journals and disseminated to patient organisations and media.

This is an international, multicenter, prospective, cohort study. Eligible patients are operated or receive best oncological treatment with a 1:1 ratio with a sequential computer-generated random number as subject ID. Intraoperative mapping techniques and/or surgical adjuncts can be used in both treatment arms to ensure the safety of the resection (to minimize the risk of postoperative deficits).

Study patients undergo tumor re-resection or receive best oncological treatment and will undergo evaluation at presentation (baseline) and during the follow-up period at 6 weeks, 3 months, and 6 months postoperatively. Motor function will be evaluated using the NIHSS (National Institute of Health Stroke Scale) and MRC (Medical Research Council) scale. Language function will be evaluated using a standard neurolinguistic test-battery consisting of the Aphasia Bedside Check (ABC), Shortened Token test, Verbal fluency, Picture description and Object naming. This neurolinguistic test-battery is the result of a consensus between the participating centers. Cognitive function will be assessed using the Montreal Cognitive Assessment (MOCA). Overall patient functioning with be assessed with the Karnofsky Performance Scale (KPS) and the ASA (American Society of Anesthesiologists) physical status classification system for comorbidities. Health-related quality of life (HRQoL) will be assessed with the EQ-5D questionnaire and the EORTC QLQ-C30 and EORTC QLQ-BN20 questionnaires. Overall survival and progression-free survival will be assessed. We expect to complete patient inclusion in 4 years. The estimated duration of the study, including follow-up, will be 5 years.

The primary study objective is to evaluate the safety and efficacy of re-resection versus best oncological treatment (neurological morbidity and overall survival) in recurrent glioblastoma patients as expressed by NIHSS scores and survival data. Secondary study objectives are to study the overall progressive-free survival (PFS), long-term neurological morbidity (3 months and 6 months postoperatively), health-related quality of life (HRQoL), and Serious Adverse Events (SAEs) after resection versus best oncological treatment as expressed by progression on follow up MRI scans based on the RANO criteria24 for tumor progression; NIHSS scores, quality of life questionnaires (EORTC QLQ C30, EORTC QLQ BN20, EQ-5D), and registration of SAEs.

Patients will be recruited for the study from the neurosurgical or neurological outpatient clinic or through referral from general hospitals of the participating neurosurgical hospitals of the ENCRAM Research Consortium, located in Europe and the United States.

The RECSUR-study: Resection Versus Best Oncological Treatment for Recurrent Glioblastoma (ENCRAM 2302)

The RECSUR-study: Resection Versus Best Oncological Treatment for Recurrent Glioblastoma: Study Protocol for An International Multicenter Prospective Cohort Study (ENCRAM 2302)

Time from diagnosis to death from any cause

NIHSS deterioration of 1 point or more at 6 weeks after surgery

NIHSS deterioration of 1 point or more at 3 months after surgery

NIHSS deterioration of 1 point or more at 6 months after surgery

Time from diagnosis to disease progression (occurrence of a new tumor lesions with a volume greater than 0.175 cm3, or an increase in residual tumor volume of more than 25%) or death, whichever comes first

Residual tumor volume of the contrast-enhancing and non-contrast enhancing part, as assessed by a neuroradiologist on postoperative MRI scan (T1 with contrast and FLAIR sequences) using manual or semi-automatic volumetric analyses (Brainlab Elements iPlan CMF Segmentation, Brainlab AG, Munich, Germany; or similar software)

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
One Time Injection of Bacteria to Treat Solid Tumors That Have Not Responded to Standard Therapy	NCT00358397	Tumors	Clostridium nov...	18 Years -	Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
The RECSUR-study: Resection Versus Best Oncological Treatment for Recurrent Glioblastoma (ENCRAM 2302)	NCT06283927	Glioblastoma Glioblastoma Mu... Glioblastoma, I... Glioblastoma Mu... Glioblastoma Mu... Recurrent Gliob... Astrocytoma, Ma... Astrocytoma of ...	Re-resection Temozolomide Lomustine Re-irradiation Experimental th... Best supportive...	18 Years - 90 Years	Erasmus Medical Center

Spots Global Cancer Trial Database for experimental therapy