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

Temozolomide

AQ4N

Antineoplastic Agents, Alkylating

Alkylating Agents

Radiotherapy

Emese Filka

Tim Clughsey, MD

Lilia Gallot

Jeffrey Raizer, MD

Ruth Ann Beasse

Tom Mikkelsen, MD

Velmeca McCrea

David Reardon, MD

Stephanie Peschka, RN

Karen Fink, MD

Phase 1b of the study, will evaluate the safety and tolerability of AQ4N treatment at three different dose levels.

Phase 2a of the study, will further evaluate the safety, tolerability, and in addition efficacy of AQ4N treatment at a tolerated dose selected from Phase 1b.

AQ4N in Combination With Radiotherapy and Temozolomide in Subjects With Newly Diagnosed Glioblastoma Multiforme

A Phase 1b/2a, Multicenter, Open-Label Study of AQ4N in Combination With Radiation Therapy and Temozolomide, to Evaluate the Safety, Tolerability, and Efficacy in Subjects With Newly Diagnosed Glioblastoma Multiforme

Novacea

Symptoms and General Pathology

Recurrence

Anaplastic Astrocytoma

All patients will receive temozolomide (150 to 200 mg per square meter for 5 days during each 28 day cycle) for a total of 1 year or until the time of disease progression.

All patients will receive 0.5 Gy of radiation therapy twice daily. This study will include a safety run-in component. If \> 33% of patients in the initial cohort of 6 experience grade 3 or greater hematologic toxicity according to the NCI Common Toxicity Criteria version 4, then a dose reduction will occur following the schedule listed below. Otherwise, following a 1 month waiting period after the first cycle of adjuvant LDFRT plus temozolomide for the first cohort of patients, the phase 2 study will open for full accrual. Patients will receive radiation with the first six 28-day cycles of temozolomide.

All patients will receive 0.5 Gy of radiation therapy twice daily. This study will include a safety run-in component. If \> 33% of patients in the initial cohort of 6 experience grade 3 or greater hematologic toxicity according to the NCI Common Toxicity Criteria version 4, then a dose reduction will occur following the schedule listed below.

Low Dose Fractionated Radiation Therapy (LDFRT)

All patients will receive temozolomide (150 to 200 mg per square meter for 5 days during each 28 day cycle) for a total of 1 year or until the time of disease progression.

Kristin Redmond, M.D.

To evaluate the safety and effectiveness of low dose rate radiation therapy plus temozolomide. This will be in patients with High Grade Glioma (to only include Anaplastic Astrocytoma or Glioblastoma Multiforme) who have previously been treated with surgery followed by radiation surgical resection followed by adjuvant radiation therapy plus temozolomide.

In vitro and in vivo studies have suggested that low dose fractionated radiation therapy (LDFRT) may be used to potentiate full dose chemotherapy, decreasing the development of resistance found with standard doses of radiation and chemotherapy. This is a nonrandomized, open label, single institution phase II trial with a safety run-in to evaluate the safety and efficacy of LDFRT plus temozolomide in patients with High Grade Glioma (to only include Anaplastic Astrocytoma or Glioblastoma Multiforme) previously treated with surgical resection followed by adjuvant radiation therapy plus temozolomide. The primary objective of the phase II study is to estimate response rate in patients treated with twice daily fractions of low dose radiation plus temozolomide chemotherapy.

Low Dose Radiation Therapy for Glioblastoma Multiforme

A Phase II Trial of Low Dose Fractionated Radiation Therapy as a Chemo-Potentiator of Salvage Temozolomide for Recurrent Anaplastic Astrocytoma and Glioblastoma Multiforme

To estimate the response rate to salvage temozolomide plus LDFRT.

Overall survival rate is calculated as the median number of months that patients were alive for the cohort

Progression free survival rate is calculated as the median number of months for the cohort until patient's disease worsened/progressed

The number of patients with grade 3+ hematologic toxicities.

The number of patients with reported grade 3+ neurologic toxicities

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Other (Not Including Serious) Adverse Events data was not collected.

All patients will receive temozolomide (150 to 200 mg per square meter for 5 days during each 28 day cycle) for a total of 1 year or until the time of disease progression.

All patients will receive 0.5 Gy of radiation therapy twice daily. This study will include a safety run-in component. If \> 33% of patients in the initial cohort of 6 experience grade 3 or greater hematologic toxicity according to the NCI Common Toxicity Criteria version 4, then a dose reduction will occur following the schedule listed below. Otherwise, following a 1 month waiting period after the first cycle of adjuvant LDFRT plus temozolomide for the first cohort of patients, the phase 2 study will open for full accrual. Patients will receive radiation with the first six 28-day cycles of temozolomide.

Low Dose Fractionated Radiation Therapy (LDFRT): All patients will receive 0.5 Gy of radiation therapy twice daily. This study will include a safety run-in component. If \> 33% of patients in the initial cohort of 6 experience grade 3 or greater hematologic toxicity according to the NCI Common Toxicity Criteria version 4, then a dose reduction will occur following the schedule listed below.

Temozolomide: All patients will receive temozolomide (150 to 200 mg per square meter for 5 days during each 28 day cycle) for a total of 1 year or until the time of disease progression.

Temozolomide With Low Dose Fractionated Radiation Therapy

Age, Continuous

Sex: Female, Male

white

black

other

Race/Ethnicity, Customized

United States

Region of Enrollment

met baseline criteria per protocol

Kristin Redmond, MD

Response Rate

Overall Survival Rate

Progression Free Survival Rate

Number of Patients With Hematologic Toxicities

Number of Patients With Neurologic Toxicity

Overall Study

Immunomodulating Agents

Leukapheresis before start of radiotherapy. Immunization with DCs starting first week after finalizing radiotherapy (2Gy x 30) and concomitant temozolomide.

Radiotherapy (2 Gy x30) with concomitant and adjuvant temozolomide.

Dendritic cell immunization

After a 4-week break, patients were then to receive up to six cycles of adjuvant temozolomide according to the standard 5-day schedule every 28 days at 150 mg per square meter for the first cycle and thereafter increase to 200 mg per square meter beginning with the second cycle.

Adjuvant temozolomide

Einar O Vik-Mo, MD, PhD

Soveig Bringsli

Solveig Bringsli

Iver A Langmoen, MD, PhD

Open, randomized study of a trivalent dendritic cell therapy compared to standard therapy in primary treated patients with IDH wild-type, MGMT-promotor methylated glioblastoma. The IMP is dendritic cells transfected with mRNA of survivin, hTERT og autologous tumor stem cells derived from tumorspheres.

Autologous leukapheresis for enrichment of PBMCs is performed after enrollment of the patient into the trial. Ex vivo generated DCs will be frozen and stored in the vapour phase of liquid nitrogen.

At first surgery, tumor biopsies will be cultured under sphere-forming conditions under ex vivo conditions for enrichment of glioblastoma stem cells. mRNA will purified and amplified from these autologous tumor stem cells.

At specified intervals patients randomized to the vaccine group will receive intradermal injections of DCs transfected with mRNA from autologous tumor stem cells, survivin and hTERT. Injections will be given as three separate injections at three separate sites.

Vaccination will be continued for as long as there are vaccines available.

Dendritic Cell Immunotherapy Against Cancer Stem Cells in Glioblastoma Patients Receiving Standard Therapy

Open Label Randomized Phase II/III Trial of Dendritic Cell Immunotherapy Against Cancer Stem Cells in Glioblastoma Patients Receiving Standard Therapy (DEN-STEM)

Defined as time from first surgery to first certain progress of contrast enhancing tumor or clinical progression, according to the Response Assessment in Neuro-Oncology (RANO) criteria.

Evaluated by EORTC Quality of Life Questionaire (QLQ-C30), a questionnaire developed to assess the quality of life of cancer patients. Scale 30 to 120 points, where higher is worse.

Evaluated by EORTC Quality of Life Questionaire, Brain module (QLQ-BN20). The brain cancer module is meant for use among brain cancer patients varying in disease stage and treatment modality. Scale 20 to 80 points, where higher is worse. It should always be complemented by the QLQ-C30.

Evaluated by delayed type hypersensitivity reaction in skin.

Classified according to Common Terminology Criteria for Adverse Events (CTCAE).

Oslo University Hospital

Senior consultant

Patients will receive dose-intensified, adaptive photon radiation therapy

Adaptive, dose-intensified radiotherapy targeting an advanced imaging signature, with a target, nominal radiotherapy dose of 80 Gy.

Dose-Intensified Radiotherapy

Temozolomide chemotherapy (75 mg/m2 daily for 6 weeks)

Adjuvant temozolomide will be delivered at 150-200 mg/m2 days 1-5 every 28 days for 6 cycles, with additional cycles delivered at the discretion of the investigator.

Michelle Kim, MD

This study will investigate whether or not intensified radiation therapy adapted during the radiation treatment course to high-risk, treatment-resistant tumor regions will improve overall survival in patients with newly diagnosed glioblastoma (GBM) compared to conventional chemoradiotherapy.

Multiparametric MR-Guided High Dose Adaptive Radiotherapy With Concurrent Temozolomide in Patients With Newly Diagnosed Glioblastoma

A Phase II Study of Multiparametric MR-Guided High Dose Adaptive Radiotherapy With Concurrent Temozolomide in Patients With Newly Diagnosed Glioblastoma

12-month overall survival rate of study participants (failure defined as death due to any cause)

Overall survival (failure defined as death due to any cause)

Progression-free survival (failure defined as progression or death due to any cause) will be evaluated using standard response assessment in neuro-oncology (RANO) criteria.

Patterns of failure (tumor growth) will be classified as follows:

* Central: \>95% of the tumor volume is within the high-dose radiation region
* In-field: \>80% to 95% of the tumor volume is within the high-dose radiation region
* Marginal: 20-80% of the tumor volume is within the high-dose radiation region
* Distant: \<20% of the tumor volume is within the high-dose radiation region

GTV is defined as the combined hypercellularity tumor volume and hyperperfused tumor volume, assessed by high b-value diffusion MRI and dynamic contrast-enhanced perfusion MRI, respectively. Patients will be grouped into those with less than 2.5 cc GTV and those with 2.5 cc or more GTV. This measure will be used to determine whether advanced MRI metrics can be used to distinguish pseudoprogression from true tumor progression, and to determine whether advanced MR-identified tumor volume 3 months post-chemoradiation is associated with survival.

The European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire C30 (EORTC QLQ-C30) is a validated questionnaire developed to assess the quality of life of cancer patients, with the EORTC QLQ-BN20 specifically for brain tumor patients. Patients will be classified as having deterioration if there is a clinically meaningful change (10 point drop from baseline) in the QOL scales. The percentage of patients with deterioration in each survey will be reported.

The MD Anderson Symptom Inventory for Brain Tumor (MDASI-BT) is a validated questionnaire developed to assess the symptom burden of brain tumor patients. Severity of symptoms is scored on a scale of 0-10, with 0 being "not present" and 10 being "as bad as you can imagine." Patients will be classified as having deterioration if there is a clinically meaningful change (1 point increase in symptom severity from baseline). The percentage of patients with deterioration will be reported.

Objective neurocognitive function (NCF) testing using Hopkins Verbal Learning Tests, Controlled Oral Word Association, and Trail Making Tests A and B. Test results will be reported as a composite, using the reliable change index (RCI) to categorize patients as improved, stable, or declined from baseline.

Rate of grade 3 or higher toxicities (neurologic and non-neurologic) of dose-intensified, adaptive chemoradiotherapy. Toxicity assessed according to the NCI Common Terminology Criteria for Adverse Events (CTCAE), version 5.0.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
AQ4N in Combination With Radiotherapy and Temozolomide in Subjects With Newly Diagnosed Glioblastoma Multiforme	NCT00394628	Glioblastoma Mu...	AQ4N Temozolomide Radiotherapy	18 Years -	Novacea
Low Dose Radiation Therapy for Glioblastoma Multiforme	NCT01466686	High Grade Glio...	Low Dose Fracti... Temozolomide	18 Years - 100 Years	Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Dendritic Cell Immunotherapy Against Cancer Stem Cells in Glioblastoma Patients Receiving Standard Therapy	NCT03548571	Glioblastoma	Dendritic cell ... Adjuvant temozo...	18 Years - 70 Years	Oslo University Hospital
Low Dose Radiation Therapy for Glioblastoma Multiforme	NCT01466686	High Grade Glio...	Low Dose Fracti... Temozolomide	18 Years - 100 Years	Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Multiparametric MR-Guided High Dose Adaptive Radiotherapy With Concurrent Temozolomide in Patients With Newly Diagnosed Glioblastoma	NCT04574856	Glioblastoma	Dose-Intensifie... Temozolomide Adjuvant temozo...	18 Years -	University of Michigan Rogel Cancer Center
AQ4N in Combination With Radiotherapy and Temozolomide in Subjects With Newly Diagnosed Glioblastoma Multiforme	NCT00394628	Glioblastoma Mu...	AQ4N Temozolomide Radiotherapy	18 Years -	Novacea

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