Neoplasms

All Conditions

Rare Diseases

Glioblastoma

Astrocytoma

Glioma

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

Anti-Infective Agents

Amino Acids

Temozolomide

Eflornithine

Antineoplastic Agents, Alkylating

Alkylating Agents

Antiprotozoal Agents

Antiparasitic Agents

Enzyme Inhibitors

Ornithine

Eflornithine 2.3 g/m2 administered orally every 8 hours on a 2 weeks on, 2 weeks off schedule

Eflornithine (Dose Level 1)

Eflornithine 2.8 g/m2 administered orally every 8 hours on a 2 weeks on, 2 weeks off schedule

Eflornithine (Dose Level 2)

Eflornithine 1.75 g/m2 administered orally every 8 hours on a 2 weeks on, 2 weeks off schedule

Eflornithine (Dose Level -1)

Temozolomide 150 mg/m2 (with option to escalate per USPI maintenance phase instructions) administered orally once daily on a 5 days on, 23 days off schedule

Monika Varga

Thiru Pillay

Louis B Nabors, MD

Meghan Gauronskas

Angela Dunn

Tobias Walbert, MD, PhD, MPH

Maria Diaz, MD

Alicia Bargo

Erin Severance

Annick Desjardins, MD, FRCPC

David Peereboom, MD

Rachel Hufsey, RN

Nuno Rodrigues, RN

Francesca Rothell, MS

Eric Wong, MD

Carlos Kamiya Matsuoka, MD

Evguenia Gachimova, RN

Rachel Kingsford

Yuri Kida

Howard Colman, MD, PhD

The purpose of this study is to establish the recommended phase 2 dose of eflornithine in combination with temozolomide in patients whose glioblastoma is newly diagnosed, and to evaluate safety and tolerability of this combination at that dose.

This open label dose escalation and expansion study will be conducted using a standard dose-escalation design with escalating doses of eflornithine plus temozolomide at the approved dose level, followed by an expansion cohort that will further evaluate safety and preliminary efficacy of the combination at the recommended phase 2 dose.

Duration of participation will be up to 56 weeks in total per patient:

Screening Period - A maximum screening duration of 4 weeks.

Treatment Period - Up to 48 weeks.

Follow-Up Visit - 4 weeks from last treatment.

A total of up to 66 patients will be enrolled in a non-randomized fashion (patients may be added to any of the dose levels below the RP2D to a maximum of approximately 20 per dose level with the intent of further characterizing safety and pharmacokinetics).

Evaluation of Eflornithine Plus Temozolomide in Patients With Newly Diagnosed Glioblastoma

An Open-label, Phase 1b Study to Evaluate the Safety and Tolerability of Eflornithine Plus Temozolomide in Patients With Newly Diagnosed Glioblastoma

Protocol Defined Dose Limiting Toxicities

Change from Baseline in Heart Rate and Respiratory Rate

Change from Baseline in Systolic Blood Pressure and Diastolic Blood Pressure

Assessment of change in QTcF relative to plasma concentration of eflornithine

Orbus Therapeutics, Inc.

Symptoms and General Pathology

Recurrence

Participants will receive Debio 0123, escalating doses along with temozolomide (TMZ) in each 28-day cycle for up to 2 years.

Participants will receive Debio 0123, escalating doses along with TMZ and concomitant administration of radiotherapy (RT) for up to 6 weeks.

Participants will receive Debio 0123 RP2D along with TMZ in each 28-day cycle for up to 2 years.

Debio 0123

Administered in accordance with the local clinical practice and applicable Radiation Therapy Oncology Group (RTOG) or the European Organization for Research and Treatment of Cancer (EORTC) guidelines.

Radiotherapy

Debiopharm International S.A

Study Director

The primary purpose of Phase 1 (dose escalation) of this study is to identify the recommended Phase 2 dose (RP2D) of Debio 0123 in combination with temozolomide (TMZ) (Arm A) and in combination with TMZ and radiotherapy (RT) (Arm B) and to characterize the safety and tolerability of these combinations in adult participants with glioblastoma (GBM).

The primary purpose of Phase 2 of this study is to assess the efficacy of Debio 0123 at the RP2D in combination with TMZ, compared to standard of care (SOC) in adult participants with GBM.

Parallel assignment applies to the arm groups within Phase 1 of the study. Sequential assignment will apply to Phases 1 and 2 of the study.

A Study of Debio 0123 in Combination With Temozolomide in Adult Participants With Recurrent or Progressive Glioblastoma and of Debio 0123 in Combination With Temozolomide and Radiotherapy in Adult Participants With Newly Diagnosed Glioblastoma

A Phase 1/2 Open-label Study of Debio 0123 in Combination With Temozolomide in Adult Participants With Recurrent or Progressive Glioblastoma and of Debio 0123 in Combination With Temozolomide and Radiotherapy in Adult Participants With Newly Diagnosed Glioblastoma

KPS is an assessment tool for functional impairment. It is a standard way of measuring the ability of participants with cancer to perform ordinary tasks. The KPS scores range from 0 (death) to 100 (no evidence of disease). A higher score means the participant is better able to carry out daily activities.

The pharmacokinetics (PK) of Debio-0123 and its metabolite will be evaluated in plasma.

The PK of temozolomide will be evaluated in plasma.

Debiopharm International SA

María del Mar Álvarez-Torres

Juan Miguel García-Gómez

The main purposes of this study are:

I. To assess that the four habitats within the tumor (HAT and LAT) and edema (IPE and VPE) in high-grade glioma are different at vascular, tissular, cellular and molecular levels.

II. To analyze the associations between the perfusion imaging markers and relevant molecular markers at the HTS habitats for high-grade glioma diagnosis, prognosis/aggressiveness, progression and/or prediction.

III. To analyze the associations between the perfusion imaging markers and immune markers at the HTS habitats useful in immunotherapy evaluation and/or patient selection.

IV. To prospectively validate the prognostic capacity (association with OS and PFS) and stratification capacity of the perfusion imaging markers calculated at the HTS habitats.

High-grade glioma (HGG) are the most aggressive malignant primary brain tumor in adults with a median survival rate of 12-15 months. It still carries a poor prognosis despite aggressive treatment, which includes tumor resection followed by chemo-radiotherapy cycles. The inter-patient and intra-patient tumor heterogeneity is one of the responsible factors for the high aggressiveness of solid malignant tumors and their resistance against effective therapies.

Due to the extremely complex and heterogeneous biology of this tumor, the same treatment for all approach does not work well in this disease, and standard of care is not always the best option, calling for precision medicine to select the best therapeutic option in the right moment to each patient. This requires quantitative medical imaging, patient profiling, prognosis estimation, and expected response to treatment for objective decision making along with the patient management.

The Hemodynamic Tissue Signature (HTS) methodology, included in the ONCOhabitats site (www.oncohabitats.upv.es), provides an automated unsupervised method to describe the heterogeneity of the enhancing tumor and edema areas in terms of the angiogenic process located at these regions. HTS considers 4 habitats within the tumour: 1) the HAT habitat, which refers to the high angiogenic enhancing tumor part of the tumour, 2) the LAT habitat, which refers to the less angiogenic enhancing tumor area of the tumour, 2) the IPE habitat, which refers to the potentially infiltrated peripheral edema, and 4) the VPE habitat, which refers to the vasogenic peripheral edema of the tumour (Juan-Albarracin et al, 2016). Perfusion imaging markers, such as relative cerebral blood volume, can be calculated from these different vascular habitats, and they have been proven as clinically relevant for prognosis. The HTS methodology, as well as the prognostic capacity of these perfusion imaging markers, have been validated with a retrospective multicenter study that included 184 high-grade glioma patients from 7 European centers.

Furthermore, relevant associations have been found between the perfusion markers and clinical-routine biomarkers, such as IDH mutation, MGMT methylation (Fuster-Garcia et al, 2020), molecular subtype or microvessel area.

Considering these promising results and, in order to develop a decision support system based on pixel level Artificial Intelligent models for deciding treatment in high-grade glioma, it is necessary to develop a prospective study and to validate at biological level the vascular habitats defined by the HTS methodology.

The proposed objectives are based on the following hypothesis:

I. Since the tumor and edema HTS habitats (HAT, LAT, IPE and VPE) have been proven as different in relation to their hemodynamic and vascular behavior, the main hypothesis are that these are habitats are also significantly different at the vascular, tissular, cellular and molecular level.

II. Significant associations between the perfusion imaging markers calculated with the HTS methodology and both molecular and histopathological markers (useful in prognosis, monitoring and evaluation of therapies) have been found in previous studies. Therefore, the hypothesis are that relevant associations between the imaging markers and clinical-routine biomarkers, such as molecular and histopathological markers, exist.

III. Preliminary studies have shown associations between the perfusion imaging markers and molecular markers related with the immune action/suppression. In addition, previous works have demonstrated that immune and genomic correlates of response to immunotherapy treatments, such as anti-PD-1, in glioblastoma. Therefore, to find correlations between these immune and genomic signatures with perfusion imaging markers can be useful for decision making and evaluation of immunotherapies.

IV. Preliminary retrospective studies have demonstrated robust association between the perfusion imaging markers calculated at high and low angiogenic habitats and patient overall survival. These robust associations between the perfusion imaging markers and survival times will be demonstrated with a prospective study.

BIOhabitats: Biological Validation of Vascular Habitats Within Astrocytoma Grade 4 at Molecular, Cellular, and Histopathological Levels

Molecular profile of each vascular habitat biopsied for each included patient, including main molecular alterations typically found in astrocytoma grade 4

Description at cellular level of each vascular habitat biopsied for each included patient, including cell types and cell density

Description at histopathological level of each vascular habitat biopsied for each included patient, including tissues, necrosis, vascularuture

Hospital Clínico Universitario de Valencia

Hospital Universitario 12 de Octubre

Juan M Garcia-Gomez

Main Researcher. Head of Biomedical Data Science Lab at UPV

Micronutrients

Vasodilator Agents

Lipid Regulating Agents

Hematinics

Vitamins

Niacinamide

Niacin

Nicotinic Acids

Vitamin B Complex

Trace Elements

Folic Acid

Hypolipidemic Agents

Antimetabolites

Nicotinamide

Nicotinic Acid

Vitamin B3

Folate

Vitamin B9

Niacin controlled release technology (CRT):

Niacin CRT™ is to be started 7 days before concurrent Radiation Therapy (RT)- Temozolomide (TMZ) treatment.

Chemo/Radiation Therapy:

For all patients, regardless of the phase of the study, concurrent RT and TMZ for 6 weeks followed by 6-12 cycles of monthly TMZ will be given.

Concurrent Temozolomide:

TMZ will be administered from the first to the last day of RT at 75 mg/m2 orally (PO) for a maximum of 49 days.

Monthly Temozolomide:

Cycles of chemotherapy Day 1 to Day 5 every 28 days will start 28 days (+/- 2 days) after the end of RT-TMZ. First cycle of TMZ is administered at 150 mg/m2 Day 1-Day 5 by mouth (PO) and increased to 200 mg/m2 Day 1-Day 5 PO from cycle 2 onwards if well tolerated. While 6 cycles are standard of care, the Neuro-Oncologist may continue up to 12 cycles if clinically appropriate.

A controlled release technology (CRT) tablet of Niacin

Niacin CRT

Gloria Roldan Urgoiti, MD

Kelsey Meyer

This is a single institution Phase I-II study to evaluate the tolerability and Maximum Tolerated Dose (MTD) (Phase I) and efficacy (Phase II) of adding Niacin CRT™ to standard first line treatment (concurrent Radiation Therapy (RT) and Temozolomide (TMZ) following by monthly TMZ - AKA Stupp protocol) in patients with newly diagnosed glioblastoma isocitrate dehydrogenase (IDH) wild type.

During the Phase I stage Niacin CRT™ dose will be escalated every 4 weeks until the maximum tolerated dose (MTD) is determined. The MTD dose will be prescribed to patients during the Phase II stage.

During the Phase I study a sample of blood at baseline, at each level dose of Niacin CRT™, and every two months during the maintenance phase while on Niacin CRTTM will be sent to a lab to evaluate the peripheral activity of Niacin CRT™ in innate immune system cells. These samples will be taken at the time of routine standard of care lab work.

Based on prior clinical trials evaluating niacin extended release formulation for the management of dyslipidaemias there is vast experience on dose escalation of niacin. One of the main side effects is flushing that is ameliorated by escalating doses in intervals no shorter than 4 weeks and usually decreases with time.

Following this schema, there is no increase in dose coinciding with TMZ while administered in a 5/28 days schedule (given daily for 5 days of each 28-day cycle). This will not only improve tolerance but also will allow us to differentiate potential adverse events from chemotherapy from the ones from Niacin CRT™.

Study of Niacin in Glioblastoma

A Phase I-II Study of Niacin in Patients With Newly Diagnosed Glioblastoma Receiving Concurrent Radiotherapy and Temozolomide Followed by Monthly Temozolomide

To evaluate and determine maximum tolerated dose (MTD) of Niacin CRT added to concurrent radiotherapy (RT) and temozolomide (TMZ) in patients with newly diagnosed glioblastoma (GB).

To evaluate if adding Niacin CRT to current standard first line treatment of GB improves progression free survival (PFS) at 6 months.

To evaluate the effect of Niacin CRT in peripheral monocytes by comparing control monocytoid cells to those that have been treated with Niacin.

To determine the response rate associated with the investigational regimen.

To determine the overall survival (OS) associated with the investigational regimen.

To determine Quality of Life (QOL) that will be evaluated throughout the study using EORTC QLQ-C30 questionnaires.

To determine Quality of Life (QOL) that will be evaluated throughout the study using EORTC BN-20 questionnaires.

Tom Baker Cancer Centre

AHS Cancer Control Alberta

Patients operated for both primary and recurrent glioblastoma between 2005 and 2023 at the CHU de Bordeaux

Relapsed glioblastoma

Mathieu LARROQUETTE

Julien ENGELHARDT

Glioblastomas are the most frequent and aggressive malignant tumors of the CNS in adults, with almost systematic relapse despite treatment with surgery followed by radio-chemotherapy (STUPP protocol). The aim of this study is to better characterize transcriptomic, proteomic and metabolic changes in relapsed glioblastoma compared to the initial tumor, in order to identify new prognostic markers and potential new therapeutic targets.

Glioblastomas are the most frequent and aggressive malignant Central Nervous System (CNS) tumors in adults, with a median survival of only 14 months.

Current treatment is based on surgery followed by radiochemotherapy (STUPP protocol), unchanged since 2005. Clinical trials evaluating immune checkpoint inhibitors and targeted therapies have largely failed to demonstrate efficacy in these tumors. In order to better understand the oncogenesis of glioblastoma and identify potential new therapeutic targets, the study of the characteristics of relapsed tumors compared with the initial tumor seems relevant.

The aim of this retrospective study is to investigate the transcriptomic, proteomic and metabolic characteristics of relapsed glioblastomas reoperated at the University Hospital of Bordeaux, France, between 2005 and 2023, for which tumor material is available. These analyses will be correlated with relapse-free and overall survival of the patients.

Study of Metabolic, Transcriptomic and Proteomic Characteristics in Relapsed Glioblastoma

Study of Metabolic, Genomic and Proteomic Modifications in Relapsed Glioblastoma. Identification or Prognostic Markers in Patients Undergoing Surgery for Relapsed Glioblastoma.

Relative abondance of metabolite and differential enzyme expression in a recurrence versus primary sample

Progression-free survival of patients who underwent surgery for relapse glioblastoma after the surgery of relapse measured at time of inclusion

Overall survival of patients who underwent surgery for relapse glioblastoma after the surgery of relapse

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Evaluation of Eflornithine Plus Temozolomide in Patients With Newly Diagnosed Glioblastoma	NCT05879367	Glioblastoma, I... Glioblastoma Glioblastoma Mu... Glioblastoma ID... GBM	Eflornithine (D... Eflornithine (D... Eflornithine (D... Temozolomide	18 Years -	Orbus Therapeutics, Inc.
A Study of Debio 0123 in Combination With Temozolomide in Adult Participants With Recurrent or Progressive Glioblastoma and of Debio 0123 in Combination With Temozolomide and Radiotherapy in Adult Participants With Newly Diagnosed Glioblastoma	NCT05765812	Glioblastoma ID... Astrocytoma, Gr...	Debio 0123 Temozolomide Radiotherapy	18 Years -	Debiopharm International SA
BIOhabitats: Biological Validation of Vascular Habitats Within Astrocytoma Grade 4 at Molecular, Cellular, and Histopathological Levels	NCT05375318	Astrocytoma, Gr... Glioblastoma Glioblastoma Mu... Glioblastoma, I... Glioblastoma, I... Glioblastoma ID... Glioblastoma ID... High Grade Glio...		18 Years -	Universitat Politècnica de València
Study of Niacin in Glioblastoma	NCT04677049	Glioblastoma ID...	Niacin CRT	18 Years - 75 Years	AHS Cancer Control Alberta
Study of Niacin in Glioblastoma	NCT04677049	Glioblastoma ID...	Niacin CRT	18 Years - 75 Years	AHS Cancer Control Alberta
Study of Metabolic, Transcriptomic and Proteomic Characteristics in Relapsed Glioblastoma	NCT06430424	Relapsed Cancer Glioblastoma ID...	Relapsed gliobl...	18 Years -	University Hospital, Bordeaux
Study of Metabolic, Transcriptomic and Proteomic Characteristics in Relapsed Glioblastoma	NCT06430424	Relapsed Cancer Glioblastoma ID...	Relapsed gliobl...	18 Years -	University Hospital, Bordeaux

Spots Global Cancer Trial Database for glioblastoma idh (isocitrate dehydrogenase) wildtype