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

Antineoplastic Agents

Anti-Infective Agents

Vaccines

Imiquimod

Immunologic Factors

Immunomodulating Agents

Adjuvants, Immunologic

Interferons

Participants in this group will undergo leukapheresis after standard of care surgical tumor resection. Leukapheresis will be used to obtain peripheral blood mononuclear cells (PBMC) from which the dendritic cells (DC) will be obtained. Retrieved DC will be used as a vaccine once weekly on Weeks 1-4 within 3 weeks from end of leukapheresis. Participants will also receive Imiquimod, which will be applied one evening prior to DC dose for 8 hours then for 8 hours each of the next two evenings. Enrollment of participants in the Pilot group will be staggered until the second participant has no treatment limiting toxicities. For the first five subjects to be enrolled in the pilot, the administration of DC to each subject will be delayed until the prior subject has received the second administration of DC. Participants will also receive Lysate of tumor administered every 4 weeks + 3 days on Weeks 8, 12, 16 and 28 (+ / - 3 days).

Participants in this group will undergo leukapheresis within after standard of care surgical tumor resection. Leukapheresis will be used to obtain peripheral blood mononuclear cells (PBMC) from which the dendritic cells (DC) will be obtained. Retrieved DC will be used as a vaccine once weekly on Weeks 1-4 within 3 weeks from end of pheresis. Participants will also receive Imiquimod, which will be applied one evening prior to DC dose for 8 hours then for 8 hours each of the next two evenings. Participants will also receive Lysate of tumor administered every 4 weeks + 3 days on Weeks 8, 12, 16 and 28 (+ / - 3 days).

Between 1.2 to 12 million DC per dose administered once a week via intradermal injection for 4 weeks.

Dendritic Cell Vaccine

Post-DC Vaccine therapy. Up to 1.5 mg of Lysate of tumor per dose administered via intradermal injection at intervals defined by study protocol.

Tumor Lysate

5% topical cream applied to vaccine site before and after administrations of DC vaccine or lysate

Baseline, post-surgery blood draw via catheter to obtain peripheral blood mononuclear cells (PBMCs) from which Dendritic cells will be obtained.

Leukapheresis

Macarena De La Fuente, MD

The purpose of this research study is to evaluate an investigational vaccine using patent-derived dendritic cells (DC) to treat malignant glioma or glioblastoma.

Dendritic Cell (DC) Vaccine for Malignant Glioma and Glioblastoma

Dendritic Cell Vaccine For Malignant Glioma and Glioblastoma Multiforme in Adult and Pediatric Subjects

Adverse Events will be evaluated using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) Version 4.0 by treating physician

Rate of overall survival in study participants receiving protocol therapy. Overall survival is defined as the time elapsed from the start of treatment until death. For surviving patients, follow-up will be censored at the date of last contact.

Rate of prolonged progression-free survival in study participants receiving protocol therapy. Progression-Free Survival (PFS) is defined as the time elapsed from the start of treatment to the date of documented progression or death, whichever comes first. For surviving patients without progression who begin alternative treatment, PFS will be censored at the last date of documented progression-free status prior to starting alternative treatment. Similarly, losses to follow up will be censored at the last date of documented progression-free status.

Immune response will be reported as the change in Myeloid Derived Suppressor Cell (MDSC) levels from blood samples

Measurement of immune response will be reported as the change in red and white blood counts from blood samples evaluated in million cells/microliter

To demonstrate if the clinical parameters associated with outcomes described for patients on other DC / imiquimod protocols hold for subjects treated on this study.

Proportion of participants able to receive all administrations of DC vaccine and those who are able to receive all administration of DC vaccine and lysate will be reported.

Assistant Professor of Clinical

Symptoms and General Pathology

Nervous System Diseases

Diseases and Abnormalities at or Before Birth

Skin and Connective Tissue Diseases

Recurrence

Neurofibromatoses

Neurofibromatosis 1

Neurofibroma

Nerve Sheath Neoplasms

Syndrome

Neoplastic Syndromes, Hereditary

Neurocutaneous Syndromes

Heredodegenerative Disorders, Nervous System

Neurodegenerative Diseases

Genetic Diseases, Inborn

Peripheral Nervous System Diseases

Neuromuscular Diseases

Nervous System Neoplasms

Peripheral Nervous System Neoplasms

Neurofibromatosis

Neurofibromatosis Type 1

Antirheumatic Agents

Pharmaceutical Solutions

Hydroxychloroquine

Trametinib

Dabrafenib

Dimethyl Sulfoxide

Antimalarials

Antiprotozoal Agents

Antiparasitic Agents

Enzyme Inhibitors

Protein Kinase Inhibitors

Protective Agents

Antioxidants

LGG or HGG with BRAF V600E/D/K mutation will receive Dabrafenib, Trametinib and Hydroxychloroquine. All medications are administered orally with Dabrafenib and HCQ given twice a day and Trametinib given once per day at the assigned dose for a 28 day course. Courses may repeat until the patient meets an off treatment criteria.

LGG with BRAF duplication or fusion with any partner or LGG with NF1 will received Trametinib and Hydroxychloroquine. All medications are administered orally with Trametinib given once per day and HCQ give twice per day at the assigned dose for a 28 day course. Courses may repeat until the patient meets an off treatment criteria.

LGG with BRAF V600E/D/K mutation will receive Dabrafenib, Trametinib and Hydroxychloroquine. All medications are administered orally with Dabrafenib and HCQ given twice a day and Trametinib given once per day at the recommended Phase 2 dose for a 28 day course. Courses may repeat until the patient meets an off treatment criteria.

HGG with BRAF V600E/D/K mutation will receive Dabrafenib, Trametinib and Hydroxychloroquine. All medications are administered orally with Dabrafenib and HCQ given twice a day and Trametinib given once per day at the recommended Phase 2 dose for a 28 day course. Courses may repeat until the patient meets an off treatment criteria

LGG with BRAF duplication or fusion with any partner will receive Trametinib and Hydroxychloroquine. All medications are administered orally with Trametinib given once per day and HCQ give twice per day at the recommended Phase 2 dose for a 28 day course. Courses may repeat until the patient meets an off treatment criteria.

LGG with Neurofibromatosis Type 1 will receive Trametinib and Hydroxychloroquine. All medications are administered orally with Trametinib given once per day and HCQ give twice per day at the recommended Phase 2 dose for a 28 day course. Courses may repeat until the patient meets an off treatment criteria.

Dabrafenib capsule; Dabrafenib Dispersible Tablet

Vanetria Stokes, MS

Nina Butingan, MBS

Lindsey Hoffman, DO

Nathan Robison, MD

Michelle Monje, MD, PhD

Kathleen Dorris

Gene Hwang, MD

Elias Sayour, MD, PhD

Jason Fangusaro

Stewart Goldman

John Glod, MD

John Glod

Ira Dunkel

Natasha Pillay Smiley, DO

Ralph Salloum, MD

Alberto Broniscer, MD

Sharon DiBridge

Giles Robinson, MD

Amar Gajjar, MD

Patricia Baxter, MD

Susan Burlingame, CCRP

This phase I/II trial is designed to study the side effects, best dose and efficacy of adding hydroxychloroquine to dabrafenib and/or trametinib in children with low grade or high grade brain tumors previously treated with similar drugs that did not respond completely (progressive) or tumors that came back while receiving a similar agent (recurrent). Patients must also have specific genetic mutations including BRAF V600 mutations or BRAF fusion/duplication, with or without neurofibromatosis type 1. Neurofibromatosis type 1 is an inherited genetic condition that causes tumors to grow on nerve tissue. Hydroxychloroquine, works in different ways to stop the growth of tumor cells by killing the cells or stopping them from dividing. Trametinib and dabrafenib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving hydroxychloroquine with trametinib and/or dabrafenib may lower the chance of brain tumors growing or spreading compared to usual treatments.

In this phase I/II study, the investigators will investigate the safety and efficacy of dabrafenib + trametinib + HCQ (D+T+HCQ) and trametinib + HCQ (T+HCQ) in pediatric and young adult patients with BRAF-altered or NF1-associated gliomas who have previously received a RAF and/or MEK inhibitor. The goal of this study is to optimize the clinical effect of dabrafenib and trametinib by addressing intrinsic and acquired resistance that is well-described in V600E-mutant melanoma and for which there is preclinical and clinical evidence in pediatric gliomas. Aside from overlapping skin toxicity of dabrafenib and trametinib, which preliminarily does not appear worse in the D+T combination in adults and children, potential for ocular toxicity, which has been observed with each agent as monotherapy, will require close monitoring. An important outcome of this study will be improved understanding of resistance mechanisms and the role of autophagy in BRAF-altered or NF1-associated gliomas through sequencing of pre- and post-RAFi or MEKi tumor (when available) and measurement of autophagy inhibition in throughout protocol therapy.

Phase I:

The primary objective of the Phase I component is to estimate the maximum tolerated doses (MTD) and recommended Phase II doses (RP2D) of D+T+HCQ and T+HCQ in children and young adults with recurrent or progressive glioma treated with prior RAF and/or MEK inhibitor therapy.

Patients with BRAF V600E LGG or HGG will receive the combination of D+T+HCQ given orally in the form of capsules which must be taken whole, or an oral solution made from tablets. Hydroxychloroquine will only be administered by oral suspension. Within each combination, Dabrafenib and Hydroxychloroquine will be administered twice a day in a 28-day course. Trametinib will be administered once a day for 28 days during each course. One course is equivalent to 28 days. Therapy with either combination may continue for up to 2 years (26 courses) in the absence of disease progression or unacceptable toxicity.

Phase II Potential patients for the Phase II portion of the trial must provide magnetic resonance imaging studies for central review for screening prior to enrollment: (1) prior targeted MEK/RAF therapy baseline, (2) prior MEK/RAF therapy best response, (3) scan at off treatment, and if different from off treatment (4) scan documenting PD associated with prior MEK/RAF targeted therapy. Additional scans may be requested from the site if the required eligibility assessments cannot be completed based on these minimal imaging requirements.

In the Phase II portion of the trial, patients will continue to receive either the D +T+HCQ or T+HCQ combination at the RP2D defined in the Phase I portion. All drugs will be given continuously without a break unless required for excess toxicity. For Phase I subjects who are treated at the MTD a similar review will take place retrospectively to determine whether the patients meet the criteria to be included in the Phase II cohort.

A Trial of Dabrafenib, Trametinib and Hydroxychloroquine for Patients With Recurrent LGG or HGG With a BRAF Aberration

Phase I/II Trial of Dabrafenib, Trametinib, and Hydroxychloroquine (HCQ) for BRAF V600E-mutant or Trametinib and HCQ for BRAF Fusion/Duplication Positive or NF1-associated Recurrent or Progressive Gliomas in Children and Young Adults

Testing the safety/tolerability of adding HCQ to Dabrafenib + Trametinib or to Trametinib

Maximum plasma concentration Dabrafenib+Trametinib+Hydroxychloroquine or Trametinib +Hydroxychloroquine

AUC for Dabrafenib+Trametinib+Hydroxychloroquine or Trametinib +Hydroxychloroquine

Number of patients who meet the "better response" criteria, which is a comparison of response on this current protocol therapy versus their best response to previous RAF and/or MEK inhibitor therapy

Describe the dose limiting toxicities separately for each stratum

Proportion of patients who achieve either a partial or a complete response among those with measureable disease at enrollment.

Time from enrollment up to disease progression or death or loss to follow-up, whichever is first

Teller Grating Acuity at 55 cm in the left eye in children with tumor involving the visual pathway

Accumulation of LC3II in peripheral blood mononuclear cells

Accumulation of p62 in peripheral blood mononuclear cells

MAPK pathway aberrations (other than BRAF) assessed by whole exome sequencing

Evaluating matched primary and recurrent/progressive in tumor in plasma (and CSF if clinically indicated)

National Cancer Institute (NCI)

American Lebanese Syrian Associated Charities (ALSAC)

Pediatric Brain Tumor Consortium

Wounds and Injuries

Brain Neoplasms

Surgical Wound

Planned resection beyond the Gadolinium (GAD)-enhancing region extending to either at least 1 cm into non-enhancing tissue, or the nearest non-enhancing sulcal boundary/ventricle wall if these structures are closer than 1 cm.

Planned resection of ≥95% of the GAD-enhancing regions of tumor without expanding the resection beyond this margin.

Tissue removal beyond the GAD-enhancing region extending to either at least 1 cm into non-enhancing tissue, or the nearest non-enhancing sulcal boundary/ventricle wall if these structures are closer than 1 cm.

Supramarginal resection

Conventional (i.e. GTR) resection

Farhad Pirouzmand, MD, MSc, FRCSC

Ainy Zahid, HBSc.

Ann Needles, BSc

Seyed A Manouri, MD

Mathew Mossey

Cian OKelly, MD

Craig Spencer

Teresa Purzner, MD

Clementine k Affana

Sunit Das, MD

Jessica Grosskleg

Michael Kelly, MD

Alireza Mansouri, MD MSc FRCSC

Damon Scales, MD, PhD, FRCPC

G-SUMIT is a pilot, phase II,randomized controlled trial to evaluate the feasibility of performing a large-scale trial in patients undergoing surgery for first-time diagnosis of high grade glioma (HGG) in a surgically favorable anatomical location to answer the following:

Does extending the margin of resection 1 cm beyond visible enhanced volume on MRI result in (a) an increase in overall survival? (b) result in a similar rate of "clinically-significant" neurological worsening during 30 days post surgery and quality of life at 6 and 12 months?

This pilot, multi-centre, pragmatic randomized controlled trial is planned to simulate all aspects of a larger definitive trial comparing conventional versus supramarginal tumor resection at the time of the first surgical resection of HGG in appropriately selected patients. This pilot will help determine the ability to meet pre-specified criteria in identification, recruitment, and patient allocation, allow for refinement of eligibility criteria for optimal recruitment, confirm safety of procedure and ability to retain participants for the duration of the trial. Preliminary efficacy data will inform sample size calculations and estimation of resources required for the envisioned larger definitive trial.

Glioma Supra Marginal Incision Trial

Phase II Pilot Randomized Controlled Trial to Assess Feasibility of "Supra-marginal" Surgical Resection of Malignant Glioma

The number of patients enrolled and successfully allocated to the intervention versus the control treatment

Measures feasibility. Among all screened patients, the proportion of patients who meet the eligibility criteria

Measures feasibility. Among all screened patients, the proportion of patients consenting to participate

Measures feasibility. Among all screened patients, the proportion of patients completing all scheduled follow-up assessments

Measures feasibility. The proportion of radiographically-confirmed gross total resection of contrast-enhancing tumor based on the first MRI after surgery.

Measures efficacy. The date of death will be obtained from hospital records, outpatient follow up clinic notes, or provincial cancer registries.

Measures efficacy. Assessment of progression-free survival based on the Modified Criteria for Radiographic Response Assessment in Glioblastoma (mRANO) criteria. The date of death will be obtained from hospital records, outpatient follow up clinic notes, or provincial cancer registries. Progression-free survival will be measured based on mRANO criteria during regular 3-month interval clinical and MRI follow up

The NIH Stroke Scale (NIHSS) will be used to assess neurological function. The NIHSS is a validated neurologically-specific outcome tool originally developed for rapid grading of stroke symptoms adopted in surgical clinical trials as well.

The modified rankin scale (mRS ) is a measure of global disability that has been widely used to assess outcome after stroke.

The scale consists of six grades from 0 (no symptoms) to 5 (severe disability); 6 indicates death.

The overall quality of life will be assessed either in-person or over the phone using the EuroQol-5 (EQ-5D). The EQ-5D is a generic instrument used to measure quality of life, designed for self-completion by respondents either face-to-face or over telephone interview, also available in proxy version through care giver.

Volumetric measurement of contrast enhancement on MRI

Canadian Institutes of Health Research (CIHR)

Sunnybrook Research Institute

Sunnybrook Health Sciences Centre

Behaviors and Mental Disorders

Fatigue

Quality of Life

All patients will receive a routine clinic-based physical therapy program. This program may include supervised aerobic conditioning, strengthening exercise, balance retraining, functional activity training, therapeutic exercise, and manual therapy.

Clinic-based physical therapy program.

In addition to the clinic-based physical therapy program, patients will perform home exercises. Home exercise will include a walking and strengthening program 5 days per week. The home exercise routine will be recorded in an exercise diary.

Home exercise program.

Erin M Dunbar, MD

The purpose of this study is to find out if adding a home exercise program to a clinic physical therapy program will improve the fatigue experienced by patients being treated with concurrent chemotherapy and radiation therapy for high grade gliomas.

Cancer-related fatigue is a common and disabling symptom in patients undergoing outpatient therapies to treat their cancers. Despite a consistent increase in both awareness and research, cancer-related fatigue remains poorly understood and poorly treated by the worldwide medical community.

The physical and emotional impact of cancer-related fatigue on Activities of Daily Living and Independent Activities of Daily Living can be profound. Simple tasks such as preparing meals and performing household chores become laborious. Walking up and down the aisles of grocery stores may send a patient directly to bed for the rest of the day upon returning home. In addition, if cancer-related fatigue contributes to prolonged bed rest, the secondary development of other medical problems can further impact quality of life and possibly length of life. Furthermore, the economic impact of cancer-related fatigue includes patients taking more days off work and reducing the number of hours they are able to work. Lastly, cancer-related fatigue often impacts the psychosocial well-being and family dynamics of patients, caregivers and their families.

Exercise is the strongest non-pharmacological intervention for management of cancer-related fatigue. Certain exercises have specifically demonstrated reduction in fatigue. An exercise program that incorporates strengthening and aerobic conditioning can decrease fatigue scores. Improvements in patient-reported cancer-related fatigue through the use of exercise has been demonstrated in various diseases, such as anemia, and several cancer types, most notably breast cancer. Furthermore, home exercise programs have shown meaningful improvements in patient reported fatigue.

This study will determine the effect that the addition of a 6-week Physical Therapist-directed home exercise program has on the pattern, severity, and quality of life of patient reported fatigue.

The Effects of Adding a Home Exercise Program to a Clinical Physical Therapy Program on Cancer-Related Fatigue

The Effects of Adding a Home Exercise Program (HEP) to a Clinical Physical Therapy Program (CPTP) on the Cancer-Related Fatigue Reported by Patients Undergoing Concurrent Radiation and Chemotherapy for High-Grade Glioma (HGG)

University of Florida

Oligodendroglioma

Anaplastic Oligodendroglioma

Oligoastrocytoma

Anaplastic Oligoastrocytoma

Fluorouracil

Flucytosine

Clotrimazole

Miconazole

Antifungal Agents

Antimetabolites

All patients will receive Toca 511, a retroviral replicating vector that expresses the cytosine deaminase (CD) gene. CD converts the antifungal 5-FC to the anti-cancer drug 5-FU in cells that have been infected by the Toca 511 vector. Beginning approximately 6 weeks after administration of Toca 511, patients will begin courses of oral Toca FC at pre-specified intervals, depending on cohort, during the approximately 30 week study.

Toca 511 vector

Toca FC

Asha Das, MD

Timothy Cloughesy, MD, NO

This is a multicenter study evaluating the safety and tolerability of increasing doses of Toca 511, a retroviral replicating vector, injected into the resection cavity of patients with Grade III or Grade IV Gliomas who have elected to undergo surgical removal of their tumor. Approximately 6 weeks after injection of Toca 511, patients will begin an oral courses of Toca FC, an antifungal agent. These one week courses of Toca FC will be repeated during the approximately 30 week study. Two separate cohorts of patients treated with Toca 511 and Toca FC will also be evaluated with either of the following standard treatments for glioma: lomustine or bevacizumab. After completion of this study, all patients will be eligible for enrollment and encouraged to enter a long-term continuation protocol that enables additional Toca FC treatment cycles to be given, as well as permits the collection of long-term safety and survival data.

Study of a Retroviral Replicating Vector Combined With a Prodrug to Treat Patients Undergoing Surgery for a Recurrent Malignant Brain Tumor

A Phase 1 Ascending Dose Trial of Safety and Tolerability of Toca 511, a Retroviral Replicating Vector, Administered to Subjects at the Time of Resection for Recurrent High Grade Glioma & Followed by Treatment With Toca FC, Extended-Release 5-FC

Excluding nausea, vomiting and fatigue, any Grade 3 or higher non-hematologic toxicity or any Grade 4 or higher hematologic toxicity, felt to be related to Toca 511 or the Toca 511/Toca FC combination.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Dendritic Cell (DC) Vaccine for Malignant Glioma and Glioblastoma	NCT01808820	Malignant Gliom... Glioblastoma Mu... Anaplastic Astr... High Grade Glio...	Dendritic Cell ... Tumor Lysate Imiquimod Leukapheresis	13 Years - 99 Years	University of Miami
A Trial of Dabrafenib, Trametinib and Hydroxychloroquine for Patients With Recurrent LGG or HGG With a BRAF Aberration	NCT04201457	Low Grade Gliom... High Grade Glio... Low Grade Gliom...	Dabrafenib Trametinib Hydroxychloroqu...	1 Year - 30 Years	Pediatric Brain Tumor Consortium
Dendritic Cell (DC) Vaccine for Malignant Glioma and Glioblastoma	NCT01808820	Malignant Gliom... Glioblastoma Mu... Anaplastic Astr... High Grade Glio...	Dendritic Cell ... Tumor Lysate Imiquimod Leukapheresis	13 Years - 99 Years	University of Miami
Glioma Supra Marginal Incision Trial	NCT04737577	High Grade Glio...	Supramarginal r... Conventional (i...	18 Years - 85 Years	Sunnybrook Health Sciences Centre
The Effects of Adding a Home Exercise Program to a Clinical Physical Therapy Program on Cancer-Related Fatigue	NCT00840554	Fatigue	Clinic-based ph... Home exercise p...	18 Years -	University of Florida
Study of a Retroviral Replicating Vector Combined With a Prodrug to Treat Patients Undergoing Surgery for a Recurrent Malignant Brain Tumor	NCT01470794	Glioblastoma Mu... Anaplastic Astr... Anaplastic Olig... Anaplastic Olig...	Toca 511 vector Toca FC	18 Years - 80 Years	Tocagen Inc.
Dendritic Cell Vaccine Therapy With In Situ Maturation in Pediatric Brain Tumors	NCT01902771	Glioma Brain Cancer Brain Tumor Glioblastoma Mu... High Grade Glio...	Dendritic Cell ... Tumor Lysate Imiquimod Leukapheresis	1 Year - 29 Years	University of Miami
Dendritic Cell Vaccine Therapy With In Situ Maturation in Pediatric Brain Tumors	NCT01902771	Glioma Brain Cancer Brain Tumor Glioblastoma Mu... High Grade Glio...	Dendritic Cell ... Tumor Lysate Imiquimod Leukapheresis	1 Year - 29 Years	University of Miami
Study of Capecitabine to Treat Recurrent High Grade Gliomas	NCT00717197	Malignant Gliom...	Capecitabine	18 Years -	University of Florida
A Study of Pomalidomide Monotherapy for Children and Young Adults With Recurrent or Progressive Primary Brain Tumors	NCT03257631	Central Nervous... Medulloblastoma	Pomalidomide Pomalidomide	1 Year - 21 Years	Celgene

Spots Global Cancer Trial Database for hgg

Every month we try and update this database with for hgg cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Spots Global Cancer Trial Database for hgg

Every month we try and update this database with for hgg cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for hgg cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.