Neoplasms

All Conditions

Nervous System Diseases

Rare Diseases

Glioma

Central Nervous System Neoplasms

Nervous System Neoplasms

7 Tesla Magnetic Resonance Imaging

Questionnaire Administration

Max Wintermark

This trial investigates how well 7T MRI scan works in imaging central nervous system tumors. Diagnostic procedures, such as 7T MRI, may help find and diagnose central nervous system tumors and help measure a patient's response to earlier treatment. The goal of this trial is to learn if a new MRI system can provide better quality images than a standard MRI.

PRIMARY OBJECTIVE:

I. To estimate the contrast-to-noise ratio (CNR) for several imaging modalities in brain malignancy as compared with normal brain parenchyma separately by type of malignancy and treatment status.

SECONDARY OBJECTIVE:

I. To assess the conspicuity of each imaging modality to differentiate radiation necrosis from progressive disease.

EXPLORATORY OBJECTIVES:

I. To assess patient experience in the 7 Tesla (7T) magnetic resonance imaging (MRI) system compared to their most recent MRI examination.

II. To assess the typical significance values seen for areas of maximal brain activity associated with each functional MRI (fMRI) test.

III. To assess the geometric distortion of a radiation planning sequence on a ultra-high field (UHF) system.

OUTLINE:

Patients undergo 7T MRI over 60 minutes.

An Investigational Scan (7T MRI) for the Imaging of Central Nervous System Tumors

Validation of a Multi-Parametric Ultra-High Field MRI Protocol for Central Nervous System Malignancy

Will be summarized by the group mean and standard deviation.

Will be reported on a five-point Likert scale and compared between the 7 Tesla (7T) scan and the most recent clinical scan by using a Wilcoxon rank-sum test.

For each imaging modality, will calculate the CNR separately in the largest lesion/metastasis per patient as well as in all study lesions. The CNR for each imaging method will be determined and reported along with the corresponding 95% confidence interval. If enough follow-up images are obtained, will compare the CNR in lesions that respond to treatment to those that do not by using a Wilcoxon rank-sum test. Will compare the CNR between baseline and follow-up within patient by using a Wilcoxon signed-rank test. Also, for those lesions that initially respond, some will subsequently grow in size after the initial response. Of these, some will be considered radiation necrosis and some progressive disease. The CNR will be compared between lesions with necrosis and those that are progressive disease using a Wilcoxon rank-sum test.

The T1 sequence by MRI will be considered the gold standard, and will compare the conspicuity of each of the other methods to that of T1 sequencing by using McNemar's test. This analysis will first be performed in the largest lesion per patient, and then analyses will be repeated using all lesions.

National Cancer Institute (NCI)

M.D. Anderson Cancer Center

Neoplasms, Second Primary

Patients receive brigatinib PO QD on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

90 mg orally QD for 7 days followed by 180 mg orally QD continuously thereafter. One cycle of therapy will consist of 28 days of treatment.

Brigatinib

Laboratory Biomarker Analysis

Quality-of-Life Assessment

Sameek Roychowdhury, MD

This phase II trial studies how well brigatinib works in treating patients with ALK and ROS1 gene alterations and solid cancers that have spread to nearby tissue and lymph nodes or other places in the body. Brigatinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

PRIMARY OBJECTIVES:

I. To evaluate the overall response rate (ORR) of brigatinib in patients with advanced solid tumors harboring genomic alterations in ALK (excluding lung) and ROS1 (all solid tumors).

SECONDARY OBJECTIVES:

I. To assess the safety and tolerability of brigatinib in patients with advanced solid tumors harboring genomic alterations in ALK (excluding lung) and ROS1 (all solid tumors).

II. To assess progression free survival (PFS) and overall survival (OS) in patients with advanced ALK or ROS1 mutated solid tumors treated with brigatinib.

III. To assess sensitivity and durability of response to brigatinib in different solid tumor types.

IV. To assess the role of intertumoral and intratumoral heterogeneity in the development of resistance to brigatinib.

V. To identify candidate genomic (including circulating tumor deoxyribonucleic acid \[DNA\]) and proteomic biomarkers of tumor sensitivity and resistance to brigatinib using high-throughput approaches (exome, transcriptome, reverse phase protein array \[RPPA\]).

TERTIARY OBJECTIVES:

I. Correlation of brigatinib exposure with efficacy and safety. II. Correlation of tumor and plasma biomarkers with brigatinib efficacy and safety.

OUTLINE:

Patients receive brigatinib orally (PO) once daily (QD) on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 3 months for 52 weeks.

Brigatinib in Treating Patients With ALK and ROS1 Gene Alterations and Locally Advanced or Metastatic Solid Cancers

Phase II Study of Brigatinib for Advanced Solid Cancers Harboring Genomic Alterations in ALK (Excluding Lung) and ROS1 Oncogenes

Brigatinib exposure will be compared to RECIST measurements and adverse events measured using CTCAE v4.

Correlative and protein markers will be summarized univariately in a quantitative manner and also summarized by clinical outcome group (e.g. response vs. no response). Graphical analyses will be largely used to assess potential patterns and relationships; e.g. side-by-side boxplots to assess differences in continuous marker levels between those with vs. without the clinical improvement (e.g. response versus no response). Will correlate with efficacy and safety.

Response for tumors will be assessed using the RECIST 1.1 criteria (using computed tomography scans or calipers by clinical exam) where response will be defined as a partial or complete response. Will be calculated with 95% binomial confidence intervals for the estimate of the proportion of responses.

Will be assessed by central independent review committee per RECIST version 1.1.

Frequency and severity of adverse events and tolerability of the regimen will be collected and summarized by descriptive statistics. The maximum grade for each type of toxicity will be recorded for each patient, and frequency tables will be reviewed to determine toxicity patterns.

Kaplan-Meier curves will be used to estimate the survival distributions of overall survival.

Kaplan-Meier curves will be used to estimate the survival distributions of progression-free survival.

Will be calculated by the number of patients who have achieve a response and/or are progression-free and alive at 6 months divided by the total number of evaluable patients. Exact binomial 95% confidence intervals for clinical benefit rate will be calculated.

The logistical aspects of the trial will be evaluated and summarized. Disease group-specific outcomes will also be summarized and described, although we will not be powered for any formal evaluation within a disease or histology subset.

The logistical aspects of the trial will be evaluated and summarized. Disease group-specific outcomes will also be summarized and described, although we will not be powered for any formal evaluation within a disease or histology subset. Genes will be evaluated in aggregate from whole exome and transcriptome sequencing.

Sameek Roychowdhury

Principal Investigator

Heart and Blood Diseases

Brain Neoplasms

Mitral Valve Insufficiency

Other Dietary Supplements

All Drugs and Chemicals

Pyruvate

Participants undergo MRI over 45 minutes at baseline. Participants then receive hyperpolarized carbon C 13 pyruvate IV over 30-40 seconds. Within 1 minute, participants undergo MRSI over 3 minutes and MRI over 10 minutes.

Participants undergo MRI over 45 minutes at baseline. Participants then receive hyperpolarized carbon C 13 pyruvate IV over 30-40 seconds. Within 1 minute, participants undergo MRSI over 3 minutes and MRI over 10 minutes (participants may receive gadolinium at the discretion of the protocol director).

Gadolinium

Hyperpolarized Carbon C 13 Pyruvate

Magnetic Resonance Imaging

Magnetic Resonance Spectroscopic Imaging

Lawrence Recht

This early phase I trial studies how well hyperpolarized carbon C 13 pyruvate magnetic resonance imaging works in detecting lactate and bicarbonate in participants with central nervous system tumors. Hyperpolarized carbon C 13 pyruvate magnetic resonance imaging may be used to measure the metabolic state of malignant brain tumors.

PRIMARY OBJECTIVES:

I. To assess the safety of intravenous (IV) injection of hyperpolarized carbon C 13 pyruvate (hyperpolarized \[1-13C\] pyruvate) for magnetic resonance imaging (MRI).

II. To assess the frequency and sensitivity with which lactate and bicarbonate signals can be detected in malignant brain tumors after IV injection of hyperpolarized \[1-13C\] pyruvate.

OUTLINE:

Participants undergo MRI over 45 minutes at baseline. Participants then receive hyperpolarized carbon C 13 pyruvate IV over 30-40 seconds. Within 1 minute, participants undergo magnetic resonance spectroscopic imaging (MRSI) over 3 minutes and MRI over 10 minutes (participants may receive gadolinium at the discretion of the protocol director).

After completion of study, participants are followed up periodically.

Hyperpolarized Carbon C 13 Pyruvate Magnetic Resonance Spectroscopic Imaging in Detecting Lactate and Bicarbonate in Participants With Central Nervous System Tumors

A Pilot Study to Assess Lactate and Bicarbonate Detection Within Malignant Brain Tumors Using [1-13C]-Pyruvate DNP Magnetic Resonance Spectroscopy (MRS)

The outcome is defined as the number of participants with hyperpolarized carbon C 13 pyruvate magnetic resonance signal detection above background noise level of both lactate and bicarbonate in all tumors screened.

The measurement of this drug is the number of participants with Grade 2 or higher related adverse events (except for asymptomatic lab increases)

National Institutes of Health (NIH)

Daniel M. Spielman

Professor of Radiology

Participants undergo MRI over 45 minutes at baseline, then receive hyperpolarized carbon C 13 pyruvate IV over 30-40 seconds. Within 1 minute, participants undergo MRSI over 3 minutes and MRI over 10 minutes.

Healthy Volunteers

Participants undergo MRI over 45 minutes at baseline, then receive hyperpolarized carbon C 13 pyruvate IV over 30-40 seconds. Within 1 minute, participants undergo MRSI over 3 minutes and MRI over 10 minutes (participants may receive gadolinium at the discretion of the protocol director).

Known CNS Malignancy

Total

Age, Categorical

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

United States

Region of Enrollment

Lawrence Recht, MD

Number of Participants With Grade 2 or Higher Toxicities

Lactate and Bicarbonate Production in Tumor and Normal Brain Tissue

Overall Study

Symptoms and General Pathology

Blood and Lymph Conditions

Immune System Diseases

Skin and Connective Tissue Diseases

Recurrence

Lymphoma

Osteosarcoma

Diffuse Intrinsic Pontine Glioma

Neoplasms by Histologic Type

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

Disease Attributes

Neoplasms, Neuroepithelial

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms, Glandular and Epithelial

Neoplasms, Nerve Tissue

Neoplasms, Bone Tissue

Neoplasms, Connective Tissue

Neoplasms, Connective and Soft Tissue

Sarcoma

Brain Stem Neoplasms

Infratentorial Neoplasms

Brain Diseases

Central Nervous System Diseases

Lymphosarcoma

Neuroepithelioma

Soft Tissue Sarcoma

Patients receive CBL0137 IV over 30 minutes on days 1 and 8. Treatment repeats every 21 days for up to 17 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo bone marrow aspirate and/or biopsy at baseline, ECHO prior to cycle 1, and as clinically indicated undergo collection of blood samples throughout the trial.

Biospecimen Collection

Bone Marrow Aspirate

Bone Marrow Biopsy

Echocardiography

FACT Complex-targeting Curaxin CBL0137

Site Public Contact

Girish Dhall

Fariba Navid

Josephine H. Haduong

Kieuhoa T. Vo

Margaret E. Macy

AeRang Kim

Jonathan L. Metts

Jason R. Fangusaro

Elizabeth A. Sokol

Melissa K. Bear

Christine A. Pratilas

Steven G. DuBois

Rajen Mody

Emily G. Greengard

Kevin F. Ginn

Shalini Shenoy

Clare J. Twist

Luca Szalontay

Julia L. Glade Bender

Mitchell S. Cairo

Lars M. Wagner

Joseph G. Pressey

Bill H. Chang

Theodore W. Laetsch

Andrew Bukowinski

Jessica Gartrell

Laura J. Klesse

Sibo Zhao

Jennifer H. Foster

Matthew Dietz

Katherine G. Tarlock

David S Ziegler

This phase I/II trial evaluates the best dose, side effects and possible benefit of CBL0137 in treating patients with solid tumors, including central nervous system (CNS) tumors or lymphoma that has come back (relapsed) or does not respond to treatment (refractory). Drugs, such as CBL0137, block signals passed from one molecule to another inside a cell. Blocking these signals can affect many functions of the cell, including cell division and cell death, and may kill cancer cells.

PRIMARY OBJECTIVES:

I. To estimate the maximum tolerated dose (MTD) and/or recommended Phase 2 dose (RP2D) of FACT complex-targeting curaxin CBL0137 (CBL0137) administered via infusion on Day 1 and Day 8 of a 21-day cycle to children with recurrent or refractory solid tumors, including CNS tumors and lymphoma. (Phase 1 Dose Escalation) II. To preliminarily determine the antitumor effects as measured by objective response rate of CBL0137 in children with progressive/recurrent diffuse intrinsic pontine glioma (DIPG) and other H3 K27M-mutant diffuse midline gliomas. (Phase 2) III. To preliminarily determine the antitumor effects as measured by objective response rate or stable disease for at least 4 months of CBL0137 in children, adolescents and young adults with osteosarcoma. (Phase 2)

SECONDARY OBJECTIVES:

I. To preliminarily determine the antitumor effects of CBL0137 in children with refractory solid tumors and other CNS tumors, to the extent possible in the context of a Phase 1 study.

II. To define and describe the toxicities of CBL0137 in children with recurrent or refractory solid tumors, including CNS tumors.

III. To characterize the pharmacokinetics of CBL0137 in children with recurrent or refractory solid tumors, including CNS tumors.

EXPLORATORY OBJECTIVES:

I. To measure biologic marker FACT in tumor specimens with potential for correlation with disease response.

II. To evaluate the effect of CBL0137 on immune response by measuring the effects on the interferon response pathway in peripheral blood mononuclear cells.

III. To preliminarily determine the effect of treatment with CBL0137 on overall survival of children with DIPG or other diffuse midline gliomas, H3 K27M-mutant, in comparison with historical controls.

OUTLINE: This is a phase I, dose-escalation study followed by a phase II study.

Patients receive CBL0137 intravenously (IV) over 30 minutes on days 1 and 8. Treatment repeats every 21 days for up to 17 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo bone marrow aspirate and/or biopsy at baseline, echocardiograph (ECHO) prior to cycle 1, and as clinically indicated undergo collection of blood samples throughout the trial.

After completion of study treatment, patients are followed up at 3, 6, 9, 12, 18, 24, 36, 48 and 60 months.

CBL0137 for the Treatment of Relapsed or Refractory Solid Tumors, Including CNS Tumors and Lymphoma

A Phase 1/2 Trial of CBL0137 (NSC# 825802) in Patients With Relapsed or Refractory Solid Tumors Including CNS Tumors and Lymphoma

A descriptive analysis of biomarkers will assess associations with disease response. The parameters will be summarized with simple summary statistics, including means, medians, ranges, and standard deviations (if numbers and distribution permit). All these analyses will be descriptive and exploratory and hypotheses generating in nature. FACT expression in tumor specimens will be determined by immunohistochemistry.

Will measure effects on the interferon response pathway. A descriptive analysis of biomarkers will assess associations with disease response. The parameters will be summarized with simple summary statistics, including means, medians, ranges, and standard deviations (if numbers and distribution permit). All these analyses will be descriptive and exploratory and hypotheses generating in nature. Peripheral blood lymphocytes will be assessed for expression of genes in the interferon response pathway, in order to determine whether treatment with CBL0137 leads to increase gene expression.

Will be compared with historical controls in children with DIPG or other diffuse midline gliomas, H3 K27M-mutant.

An exploratory analysis of progression-free survival using Kaplan-Meier curves and the log-rank test statistic will compare overall time-to-disease progression (or death) versus historical cohort for the DIPG cohort.

Maximum tolerated dose (MTD) and/or recommended phase 2 dose (RP2D) of CBL0137 in children with relapsed or refractory solid tumors including CNS tumors and lymphoma.

The frequency (%) of patients experiencing a cycle 1 dose limiting toxicity attributable to CBL0137 by study part and dose level.

Frequency (%) of patients with at least partial response to CBL0137 at the maximum tolerated dose/recommended phase II dose (MTD/RP2D) in children with progressive or recurrent diffuse intrinsic pontine glioma (DIPG).

Frequency (%) of patients with complete response, partial response, or stable disease for at least 4 months to CBL0137 at the MTD/RP2D in children with Osteosarcoma.

Frequency (%) of patients with at least partial response to CBL0137 at the MTD/RP2D in children with refractory solid tumors and other central nervous system (CNS) tumors.

The frequency (%) of patients experiencing adverse events that are at least possibly attributable to CBL0137 by study part and dose level.

The median (min, max) of the area under the drug concentration curve for CBL0137 by study part and dose level.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
An Investigational Scan (7T MRI) for the Imaging of Central Nervous System Tumors	NCT04539574	Central Nervous... Glioma Metastatic Mali... Metastatic Mali...	7 Tesla Magneti... Questionnaire A...	18 Years -	M.D. Anderson Cancer Center
An Investigational Scan (7T MRI) for the Imaging of Central Nervous System Tumors	NCT04539574	Central Nervous... Glioma Metastatic Mali... Metastatic Mali...	7 Tesla Magneti... Questionnaire A...	18 Years -	M.D. Anderson Cancer Center
Brigatinib in Treating Patients With ALK and ROS1 Gene Alterations and Locally Advanced or Metastatic Solid Cancers	NCT03868423	Advanced Malign... ALK Fusion Prot... ALK Gene Amplif... ALK Gene Mutati... Locally Advance... Metastatic Mali... Metastatic Mali... Metastatic Mali... ROS1 Fusion Pos... ROS1 Gene Ampli... ROS1 Gene Mutat...	Brigatinib Laboratory Biom... Quality-of-Life... Questionnaire A...	18 Years -	Ohio State University Comprehensive Cancer Center
Hyperpolarized Carbon C 13 Pyruvate Magnetic Resonance Spectroscopic Imaging in Detecting Lactate and Bicarbonate in Participants With Central Nervous System Tumors	NCT03565367	Malignant Centr... Metastatic Mali...	Gadolinium Hyperpolarized ... Magnetic Resona... Magnetic Resona...	18 Years -	Stanford University
CBL0137 for the Treatment of Relapsed or Refractory Solid Tumors, Including CNS Tumors and Lymphoma	NCT04870944	Diffuse Midline... Metastatic Mali... Recurrent Diffu... Recurrent Lymph... Recurrent Malig... Recurrent Osteo... Recurrent Prima... Refractory Lymp... Refractory Mali... Refractory Oste... Refractory Prim...	Biospecimen Col... Bone Marrow Asp... Bone Marrow Bio... Echocardiograph... FACT Complex-ta...	12 Months - 30 Years	Children's Oncology Group
CBL0137 for the Treatment of Relapsed or Refractory Solid Tumors, Including CNS Tumors and Lymphoma	NCT04870944	Diffuse Midline... Metastatic Mali... Recurrent Diffu... Recurrent Lymph... Recurrent Malig... Recurrent Osteo... Recurrent Prima... Refractory Lymp... Refractory Mali... Refractory Oste... Refractory Prim...	Biospecimen Col... Bone Marrow Asp... Bone Marrow Bio... Echocardiograph... FACT Complex-ta...	12 Months - 30 Years	Children's Oncology Group

Spots Global Cancer Trial Database for metastatic malignant neoplasm in the central nervous system