Neoplasms

All Conditions

Nervous System Diseases

Rare Diseases

Glioblastoma

Central Nervous System Neoplasms

Gliosarcoma

Nervous System Neoplasms

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

Amino Acids

Temozolomide

Erlotinib Hydrochloride

Antineoplastic Agents, Alkylating

Alkylating Agents

Tyrosine Kinase Inhibitors

Protein Kinase Inhibitors

Enzyme Inhibitors

Tyrosine

Erlotinib is available as 25 mg, 100 mg, and 150 mg tablets. It should be administered orally once daily at the prescribed dose specified in the clinical study protocol per dose escalation schema. Preferably, erlotinib should be taken in the morning with up to 200 mL of water at least 1 hour before or 2 hours after a meal.

erlotinib hydrochloride

TMZ is supplied in white opaque, preservative-free, two piece hard gelatin capsules of the following sizes: 100mg capsules, 20mg capsules, and 5mg capsules. TMZ will be a once a day orally administered (75 mg/m2 x BSA x 42 days)set of capsules taken at least two hours after and one hour before a meal.

temozolomide

Concomitant focal RT will be delivered once daily at 2 Gy per fraction, 5 d/wk, for a total of 60 Gy. (6 weeks) as mentioned in therapeutic modalities.

radiation therapy

David M. Peereboom, MD

RATIONALE: Radiation therapy uses high-energy x-rays to kill tumor cells. Drugs used in chemotherapy, such as temozolomide, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Erlotinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving radiation therapy together with temozolomide and erlotinib after surgery may kill any remaining tumor cells.

PURPOSE: This phase II trial is studying how well giving radiation therapy together with temozolomide and erlotinib works in treating patients with newly diagnosed glioblastoma multiforme.

OBJECTIVES:

* Determine the progression-free survival and overall survival of patients with newly diagnosed glioblastoma multiforme treated with adjuvant radiotherapy, temozolomide, and erlotinib hydrochloride.
* Evaluate the toxicity of this regimen in these patients.

OUTLINE: This is a non-randomized study.

Patients receive oral temozolomide once daily on days 1-42 and undergo concurrent radiotherapy once daily on days 1-5, 8-12, 15-19, 22-26, 29-33, and 36-40. Four weeks after completion of radiotherapy and temozolomide, patients receive oral temozolomide once daily on days 1-5. Treatment with temozolomide repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity. Patients also receive oral erlotinib hydrochloride once daily beginning on day 1 of radiotherapy and continuing in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed periodically.

PROJECTED ACCRUAL: A total of 30 patients will be accrued for this study.

Radiation Therapy, Temozolomide, and Erlotinib in Treating Patients With Newly Diagnosed Glioblastoma Multiforme

A Phase II Trial of Erlotinib With Temozolomide and Concurrent Radiation Therapy Post-Operatively in Patients With Newly Diagnosed Glioblastoma Multiforme

National Cancer Institute (NCI)

David Peereboom

Principal Investigator

Symptoms and General Pathology

Diseases and Abnormalities at or Before Birth

Skin and Connective Tissue Diseases

Recurrence

Carcinoma

Brain Neoplasms

Neuroblastoma

Neurofibromatoses

Neurofibromatosis 1

Neurofibroma

Neurofibroma, Plexiform

Brain Diseases

Central Nervous System Diseases

Neuroectodermal Tumors, Primitive, Peripheral

Nerve Sheath Neoplasms

Peripheral Nervous System Neoplasms

Peripheral Nervous System Diseases

Neuromuscular Diseases

Syndrome

Neoplastic Syndromes, Hereditary

Neurocutaneous Syndromes

Heredodegenerative Disorders, Nervous System

Neurodegenerative Diseases

Genetic Diseases, Inborn

Neurofibromatosis

Neurofibromatosis Type 1

Optic Pathway Glioma

If 0 of 3-6 or no more than 1 of 6 evaluable participants experience a DLT, then the dose will be escalated to Dose Level 2 and the same approach will be repeated. If 2 or more DLTs are observed on Dose Level 1 in 2-6 subjects, then further enrollment to Dose Level 1 will stop, the dose will be de-escalated to Dose Level -1 and the same approach will be repeated. The MTD will be the highest dose with \<2 DLTs in 6 patients.

Participants will receive oral avutometinib once daily twice a week, three weeks on/ 1week off, for a period of 28 days per cycle

Avutometinib

Sameer Farouk Sait, MD

Julia Glade Bender, MD

Jason Fangusaro, MD

The purpose of this study is to find out whether avutometinib is a safe treatment for advanced or recurrent solid tumor cancers in children and young adults. Researchers will look for the highest dose of avutometinib that is safe and cause few or mild side effects.

A Study of Avutometinib for People With Solid Tumor Cancers

A Multi-Center Phase I Dose Escalation Study of Avutometinib, a RAF/MEK Clamp, in Pediatric Patients With Refractory or Recurrent Solid Tumors Harboring Activating MAPK Pathway Alterations

Memorial Sloan Kettering Cancer Center supports the international committee of medical journal editors (ICMJE) and the ethical obligation of responsible sharing of data from clinical trials. The protocol summary, a statistical summary, and informed consent form will be made available on clinicaltrials.gov when required as a condition of Federal awards, other agreements supporting the research and/or as otherwise required. Requests for deidentified individual participant data can be made beginning 12 months after publication and for up to 36 months post publication. Deidentified individual participant data reported in the manuscript will be shared under the terms of a Data Use Agreement and may only be used for approved proposals. Requests may be made to: crdatashare@mskcc.org.

The primary objective is to assess the safety of avutometinib in the pediatric population. CTCAE Version 5 will be utilized for toxicity evaluation. Adverse Events should be recorded from treatment start through 30 days after the last dose of study drug.

Memorial Sloan Kettering Cancer Center

Anti-Infective Agents

Vaccines

Poly ICLC

Interferons

Immunologic Factors

IMA 950

Immunomonitoring

Pierre-Yves Dietrich, Professor

RATIONALE : IMA 950 is multi tumour-associated peptides (TUMAPs) vaccine, these peptides have been identified on primary glioblastoma multiforme (GBM) cells. Poly-ICLC is a potent vaccine adjuvant with broad innate and adaptive immune enhancing effects. IMA 950 and Poly-ICLC will be administered to patients alongside standard primary therapy for glioblastoma. This includes the alkylating drug temozolomide (TMZ). Effective vaccine-induced immune responses associated with prolonged survival have been observed in glioblastoma patients during TMZ adjuvant therapy, suggesting a possible synergistic effect. A second component of glioblastoma standard treatment is external beam irradiation of the tumor site post-surgery. As a side effect, potentially beneficial tumor-infiltrating immune cells may also be killed by radiation. However, the combination of radiation with immunotherapy has been suggested to be favorable both in pre-clinical models.

OBJECTIVES

Primary

* Tolerability and safety of IMA950 adjuvanted with Poly-ICLC when given together with temozolomide, using CTCAE V 4.0.
* Immunogenicity of IMA950 plus Poly-ICLC when given together with temozolomide.

Secondary

* 6, 9 month progression free survival (PFS) using gadolinium enhanced MRI and clinical assessment according to revised RANO criteria
* Overall survival (OS)
* Immunologic endpoints (correlation between clinical and immunological responses):
* evaluation of peptide immunogenicity by tetramer staining
* analysis of memory, activation and homing marker expression by tetramer positive cells
* analysis of cytokine secretion and proliferation by antigen-specific CD4 and CD8 T cells
* analysis of the presence of T regulatory and myeloid-derived suppressor cells
* The immunological analyses will be performed on:
* peripheral blood mononuclear cells (PBMC)
* cultures of skin punch biopsy at delayed-type hypersensitivity (DTH) site
* tumor-infiltrating lymphocytes (TIL) if brain tissue is available at recurrence

OUTLINE

This is a monocentric, open label, one cohort, safety and immunogenicity, Phase I/II study.

A maximum of 16 HLA-A2 positive patients with newly diagnosed glioblastoma will be enrolled into the study after treatment with radiation therapy and concurrent temozolomide.

All patients will receive the same dose of IMA950 with Poly-ICLC and follow the same vaccination schedule which comprises a Vaccination Induction Phase of 4 intensive vaccinations, followed by a Vaccination Maintenance Phase of five vaccinations over a longer period.

The Vaccination Induction Phase will start a minimum of 7 days after the final radiotherapy/TMZ dose of CRT and 28 days (+7 days) prior to the first scheduled dose of adjuvant TMZ.

This will ensure that all 4 vaccinations in the Induction Phase will be administered a week after immunosuppressive therapy (i.e. combined radiotherapy and temozolomide) and will finish a week prior to the start of adjuvant TMZ.

Two Phases :

Induction phase, patient receive the first 4 doses of Poly ICLC mixed with IMA 950 Peptide based vaccine (subcutaneously or IM) on days 1,8,15, and 21 in absence of unacceptable toxicity or disease progression.

Maintenance Phase, patient receive Poly ICLC mixed with IMA 950 Peptide based vaccine (SC or IM) on day 21 of each adjuvant temozolomide cycle in absence unacceptable toxicity or disease progression.

Immunomonitoring assessments will be performed at 8 time points with blood samples collection and one DTH site analysis(after vaccination 5).

Brain MRI will be performed every two months for disease assessment.

N.B. :

An amendment has been accepted by Swissmedic and Local Ethics committee on september 2014, after suboptimal immunomonitoring preliminary assessments, the schedule of administration has been changed in order to improve the immunogenicity of the vaccine, as follows :

* injection of mixed peptides and adjuvant Poly ICLC
* 4 vaccinations in the induction phase instead of 6
* one site of injection (thigh)
* two arms for the next 10 patients to be included that will be equally divided in 2 groups : one group will be vaccinated subcutaneously and the other intramuscularly.

Phase I/II Trial of IMA950 Multi-peptide Vaccine Plus Poly-ICLC in Glioblastoma

Phase I/II Study of Intradermal IMA950 Peptide-based Vaccine Adjuvanted With Intra Muscular Poly-ICLC in Combination With Temozolomide in Newly Diagnosed HLA-A2 Glioblastoma Patients

Correlation between clinical and immunological response. Blood sampling at baseline (week 4 and 5 after beginning of radiotherapy with concomitant temozolomide) and at week 10,11,12,16,19,23,27 and 31.

Punch biopsy at DTH (Delayed Type Hypersensitivity) site performed 48h after DTH skin test 7 days after Vaccination 7.

* evaluation of peptide immunogenicity by tetramer staining
* analysis of memory, activation and homing marker expression by tetramer positive cells
* analysis of cytokine secretion and proliferation by antigen-specific CD4 and CD8 T cells
* analysis of the presence of T regulatory and myeloid-derived suppressor cells

Immatics Biotechnologies GmbH

Oncovir, Inc.

University Hospital, Geneva

Professor

Oligodendroglioma

Diffuse Astrocytoma

Pilocytic Astrocytoma

Susan M. Chang, MD

RATIONALE: Drugs used in chemotherapy, such as temozolomide, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing.

PURPOSE: This phase II trial is studying how well temozolomide works in treating patients with supratentorial low-grade glioma.

OBJECTIVES:

Primary

* Determine the efficacy of temozolomide, defined as response rate (complete and partial response), in patients with supratentorial mixed low-grade glioma.

Secondary

* Assess the safety profile of temozolomide in patients with supratentorial low-grade glioma.
* Assess the time to tumor progression in patients treated with temozolomide.

OUTLINE: Patients receive oral temozolomide once daily on days 1-5. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed every 3 months for 1 year, every 4 months for 1 year, every 6 months for 1 year, and then annually thereafter.

PROJECTED ACCRUAL: A total of 120 patients will be accrued for this study.

Temozolomide in Treating Patients With Low-Grade Glioma

A Phase II Study of Temozolomide (TEMODAR) in the Treatment of Adult Patients With Supratentorial Low Grade Glioma

Assessment of treatment response was determined by MRI in conjunction with neurological examination and steroid requirement assessment derived from Macdonald's criteria. Complete response was defined as complete disappearance of lesion on consecutive MRI scans with stable or improved neuro exam and steroids. Partial response was defined as a 50% reduction in lesion size or that tumor burden was "definitely better" than prior scan with stable or improved neuro exam and steroids.

Progressive disease was defined as definite enlargement of any existing lesion or any new lesion based on modified Macdonald's criteria.

Number of participants with treatment related grade 2-4 adverse events as defined by CTCAE 3.0

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Radiation Therapy, Temozolomide, and Erlotinib in Treating Patients With Newly Diagnosed Glioblastoma Multiforme	NCT00274833	CNS Tumor, Adul...	erlotinib hydro... temozolomide radiation thera...	18 Years -	Case Comprehensive Cancer Center
A Study of Avutometinib for People With Solid Tumor Cancers	NCT06104488	Refractory Canc... CNS Tumors CNS Tumor, Adul... CNS Tumor, Chil... MAP Kinase Fami... NF1 Plexiform Neuro... Low-grade Gliom... Optic Pathway G... Neuroblastoma Primary Brain T... Solid Tumor Solid Tumor, Ad... Solid Carcinoma Central Nervous...	Avutometinib	3 Years - 30 Years	Memorial Sloan Kettering Cancer Center
Radiation Therapy, Temozolomide, and Erlotinib in Treating Patients With Newly Diagnosed Glioblastoma Multiforme	NCT00274833	CNS Tumor, Adul...	erlotinib hydro... temozolomide radiation thera...	18 Years -	Case Comprehensive Cancer Center
Phase I/II Trial of IMA950 Multi-peptide Vaccine Plus Poly-ICLC in Glioblastoma	NCT01920191	CNS Tumor, Adul...	IMA 950 Poly ICLC Immunomonitorin...	18 Years -	University Hospital, Geneva
Temozolomide in Treating Patients With Low-Grade Glioma	NCT00313729	CNS Tumor, Adul...	temozolomide	18 Years - 120 Years	University of California, San Francisco
Temozolomide in Treating Patients With Low-Grade Glioma	NCT00313729	CNS Tumor, Adul...	temozolomide	18 Years - 120 Years	University of California, San Francisco

Spots Global Cancer Trial Database for cns tumor, adult