Neoplasms

All Conditions

Rare Diseases

Glioblastoma

Glioma

Astrocytoma

Gliosarcoma

Neoplasms, Neuroepithelial

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms by Histologic Type

Neoplasms, Glandular and Epithelial

Neoplasms, Nerve Tissue

Neuroepithelioma

Antineoplastic Agents

All Drugs and Chemicals

Hematinics

Temozolomide

Liver Extracts

Antineoplastic Agents, Alkylating

Alkylating Agents

75 mg/M2 per day Intranasal Modified Temozolomide administration of within 5 days per week (max: 30 days)

150 mg/M2 per day Intranasal Modified Temozolomide administration of within 5 days per week (max: 30 days)

200 mg/M2 per day Intranasal Modified Temozolomide administration of within 5 days per week (max: 30 days)

Intranasally Modified Temozolomide is administered to patients at a dose of 75/150/200 mg / M2 for five days continuously. After the 5-day course, patients do not take treatment for two days, and they will be examined on an outpatient basis (blood tests, kidney and liver tests, visually mucous membranes of the mouth, nasal cavity, olfactory rapid tests, including the University of Pennsylvania test, etc.).

After 30 days after the first intranasal administration of Modified Temozolomide (IM-TMZ), all patients undergo an MRI of the brain with perfusion and ultrasound of the abdominal cavity as an outpatient, after which the results are evaluated

Intranasal Modified Temozolomide

The purpose of this pilot study is to determine the safety, tolerability, and the maximum tolerated dose intranasal administration of temozolomide (TMZ) as a single agent in Treatment on the patients with GBM.

Intranasal administration is a new method of treating brain tumours for the direct administration of drugs, inhibitors or viruses, with minimal involvement of the BBB. The investigators know the orally prescribed standard chemotherapy temozolomide (TMZ) is widely used to treat glioma tumours.

Received evidence of safety and efficacy in a full cycle of preclinical trials (on GLP Standart) and tests of calculated doses of intranasal administration of TMZ in healthy volunteers.

Intranasal administration of temozolomide is considered as GBM therapy, which provides direct access to a therapeutic dose of the drug into the brain (to the neoplastic process) with low toxicity

The investigators are trying to evaluate a clinically potentially effective intranasal way of delivering TMZ to the brain, taking into account the anatomical structure of os ethmoidal.

The most important factor in the effectiveness of the drug is the achievement of an adequate amount of the active agent in its unbound state with albumin on the blood of a patient and the exposure time to the tumour process. Failure to comply with this requirement (difficulties in overcoming the BBB) was identified as the main obstacle to the successful treatment of all types of brain tumours. Translation to improved clinical outcomes in a patient with GBM has not yet been realized. The investigators will use modified temozolomide (without changing the chemical formula) to exclude as much as possible Anosmia, Hyposmia and other violation of the identification of odours with participants.

Evaluate the Safety and Effectiveness of Intranasal Administration of Temozolomide in Patients With Glioblastoma

Pilot Study to Evaluate the Safety, Tolerability and Effectiveness of Intranasal Administration of Temozolomide in Patients With Glioblastoma (Phase I)

Overall survival (OS) will be determined as the time in days from the start of treatment ( randomizations day ) to death due to any cause was estimated by the Kaplan-Meier method.

If it was not known for certain that the participant to die, time will be censored at the last date the participant with GBM or Gliosarcomawas known to be alive, date of magnetic resonance imaging (MRI), etc, - assessment, which will be defined as the latest among the date of the last visit.

The effectiveness of the intranasal administration of modified Temozolomide will be evaluated by four MRIs with perfusion (first MRI performed one day before randomization day). The results of all MRI in dynamics will be appreciated by a consultation of radiologists.

Incidence of Treatment-Emergent Adverse Events will be estimated by the number of participants with Glioblastoma or Gliosarcoma according to the NCI CTC (5.0) with adverse events (AE) in all cohorts.

In the present study, the maximum dose of modified Temozolomide for intranasal administration is 200 mg / M2 a single daily intranasal administration in a course of 5 days. The frequency of adverse events, unacceptable toxicity, or haematological reactions is estimated on a scale the NCI CTCAE (v. 5.0)

Center Trials & Treatment Europe

Antibodies

Bevacizumab

Tislelizumab

Immunoglobulins

Antineoplastic Agents, Immunological

Angiogenesis Inhibitors

Growth Inhibitors

Subjects with ctDNA-level-relapse Astrocytoma before clinical relapse, determined according to the dynamics of TISF ctDNA.

Subjects with clinical-relapse Astrocytoma, determined according to the response assessment in neuro-oncology (RANO) criteria for gliomas.

Subjects without ctDNA-level-relapse and clinical-relapse Astrocytoma.

200mg sintilimab plus 3mg/kg bevacizumab every 3 weeks.

Tislelizumab plus Bevacizumab

Xingyao Bu

This is an ongoing Phase 2, open-label, single-center, non-randomized study of sintilimab (one anti-PD-1 antibody same as nivolumab approved in China) plus bevacizumab administered in a low dosage schedule in adult (≥ 18 years) participants with a clinical relapse or circulating tumor DNA (ctDNA)-level relapse of Astrocytoma. This study has three non-comparative study groups. Cohort 1 and Cohort 2 will receive the same study drug sintilimab 200mg and bevacizumab 3mg/kg every 3 weeks. Cohort 3 will take only standard treatment. A stringent three-step non-randomized process will be used to assign participants to one of the study groups. Neither participants nor doctors but the researcher can choose which group participants are in. No one knows if one study group is better or worse than the other. 70 total participants are expected to participate in this study (25 participants in Cohort 1 and Cohort 2,20 participants in Cohort 3).

Grouping process: After enrollment, under the standard of care, participants will receive regular tumor in situ fluid (fluid within the surgical cavity, TISF) sampling for ctDNA analysis and recceive regular MRI. The researcher will study the TISF ctDNA and imaging dynamics to determine whether the tumor reaches to ctDNA-level (Cohort 1) or clinical relapse (Cohort 2). At the first step, all timely identified as ctDNA-level relapse tumors will be assigned into the Cohort 1 and receive the study drug immediately, those failed to be timely identified will be assigned into the Cohort 2 and receive the study drug after the clinical relapse. At the second step, once Cohort 1 or Cohort 2 reaches the target number, the new participants will be all assigned into the other Cohort. In the third step, if no ctDNA-level or clinical relapse was observed within 60 months after surgery, patients were assigned to Cohort 3 and further analyzed for prognostic biomarkers compared with Cohort 1 and Cohort 2.

Primary study objectives:

-To evaluate the clinical efficacy as measured by the overall survival (OS) rate at 24 months (Cohort 2) and OS rate at 36 months (Cohort 1).

Secondary study objectives:

* To evaluate the safety/tolerability of the study treatment; To compare the OS, progression-free survival and overall response rate of the two study groups. Exploratory objectives:
* To evaluate the correlative biomarkers based on TISF ctDNA.

Standard of care:

-Surgical removal of tumors followed by adjuvant temozolomide (150-200 mg/m2, days 1-5 every 28 days for up to 12 cycles). The decision to extend TMZ treatment beyond 6 cycles, for up to 12 cycles, was left to the treating investigator. Patients were asked to attend follow-up visits every 3 months after the end of chemotherapy.

Sintilimab (One Anti-PD-1 Antibody) Plus Low-dose Bevacizumab for ctDNAlevel- Relapse and Clinical-relapse Astrocytoma

Phase 2 Study to Evaluate the Clinical Efficacy and Safety of Sintilimab Plus Low-dose Bevacizumab in Patients With Astrocytoma of Different Relapse Stages

OS-24 is the proportion of participants in the analysis population who remain alive for at least 24 months following initiation of study therapy.

OS-36 is the proportion of participants in the analysis population who remain alive for at least 36 months following initiation of study therapy.

The proportion of participants in the analysis population who remain progression-free for at least 18 months following initiation of study therapy.

overall survival, as defined as time from beginning of treatment to death.

Proportion of participants in the analysis population who have complete response (CR) or partial response (PR) using RANO criteria.

Participants without efficacy evalaluation data or survival data censored at day 1. Participants without measurable disease will not be included.

Median time from allocation to first documented disease progression as per RANO or death due to any cause, whichever occurs first.

Time from first RANO response to disease progression in participants who achieve a PR or better.

Toxicity is graded in accordance with the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), version 4.03. Adverse events (AEs) are reported based on clinical laboratory tests, vital sign and weight measurements, physical examinations, performance status evaluations, magnetic resonance imaging, and any other medically indicated assessments, including subject interviews, from the time informed consent is signed through 90 days after the last dose of durvalumab. AEs are considered to be treatment emergent if they occur or worsen in severity after the first dose of study treatment.

Henan Provincial People's Hospital

Symptoms and General Pathology

Behaviors and Mental Disorders

Recurrence

Disease Progression

Disease Attributes

Quality of Life

Immunomodulating Agents

Lomustine

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
Evaluate the Safety and Effectiveness of Intranasal Administration of Temozolomide in Patients With Glioblastoma	NCT04091503	Glioma, Maligna... Gliosarcoma Astrocytoma of ...	Intranasal Modi...	21 Years - 70 Years	Center Trials & Treatment Europe
Evaluate the Safety and Effectiveness of Intranasal Administration of Temozolomide in Patients With Glioblastoma	NCT04091503	Glioma, Maligna... Gliosarcoma Astrocytoma of ...	Intranasal Modi...	21 Years - 70 Years	Center Trials & Treatment Europe
Sintilimab (One Anti-PD-1 Antibody) Plus Low-dose Bevacizumab for ctDNAlevel- Relapse and Clinical-relapse Astrocytoma	NCT05518994	Astrocytoma of ...	Tislelizumab pl...	18 Years -	Henan Provincial People's Hospital
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 astrocytoma of brain