Neoplasms

All Conditions

Skin and Connective Tissue Diseases

Respiratory Tract (Lung and Bronchial) Diseases

Nervous System Diseases

Rare Diseases

Carcinoma

Melanoma

Carcinoma, Non-Small-Cell Lung

Lung Neoplasms

Melanoma, Cutaneous Malignant

Nevus

Meningeal Neoplasms

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

Neuroendocrine Tumors

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms by Histologic Type

Neoplasms, Nerve Tissue

Nevus, Pigmented

Nevi and Melanomas

Skin Neoplasms

Skin Diseases

Carcinoma, Bronchogenic

Bronchial Neoplasms

Central Nervous System Neoplasms

Nervous System Neoplasms

Intraocular Melanoma

Acral Lentiginous Melanoma

Neuroendocrine Tumor

Neuroepithelioma

Antineoplastic Agents

All Drugs and Chemicals

Nivolumab

Antineoplastic Agents, Immunological

Immune Checkpoint Inhibitors

Patients receive nivolumab IT over 5 minutes on day 1 of every cycle. Beginning in cycle 2, patients also receive nivolumab IV over 30 minutes on day 1 (4 hours after the IT dose). Cycles repeat every 14 days for 18 cycles and then every 28 days (cycles 19 and beyond) in the absence of disease progression or unacceptable toxicity. Patients will have CSF and blood specimen collection on days 1, 2, 8 of each cycle and end of treatment. Patients undergo CT or PET at baseline, cycle 5 and then every 8 weeks. Patients undergo MRI at baseline, cycles 3, 5, and then every 8 weeks.

Biospecimen Collection

Computed Tomography

Undergo lumbar puncture for cerebrospinal fluid collection

Lumbar Puncture

Magnetic Resonance Imaging

Positron Emission Tomography

Isabella C Glitza, MD

This phase I/Ib trial studies the side effects and best dose of intrathecal nivolumab, and how well it works in combination with intravenous nivolumab in treating patients with leptomeningeal disease. Immunotherapy with monoclonal antibodies, such as nivolumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread.

PRIMARY OBJECTIVE:

I. To determine the safety and/or recommended dose of intrathecal (IT) nivolumab in combination with systemic nivolumab treatment in melanoma and lung cancer with leptomeningeal disease (LMD).

SECONDARY OBJECTIVE:

I. To assess overall survival with combined intrathecal and systemic administration of nivolumab in this patient population.

EXPLORATORY OBJECTIVES:

I. Compare the immunological effects of this treatment on immune cells in the cerebrospinal fluid (CSF) to those observed in the peripheral blood and in non-LMD tumors.

II. Evaluation of predictors (clinical, molecular, and/or immune) of the efficacy and safety of this regimen.

III. To assess the effect of nivolumab on subsequent treatment. IV. To compare levels of nivolumab in the CSF and peripheral blood.

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

Patients receive nivolumab IT over 5 minutes on day 1 of every cycle. Beginning in cycle 2, patients also receive nivolumab intravenously (IV) over 30 minutes on day 1 (4 hours after the IT dose). Cycles repeat every 14 days for 18 cycles and then every 28 days (cycles 19 and beyond) in the absence of disease progression or unacceptable toxicity. Patients will have CSF and blood specimen collection on days 1, 2, 8 of each cycle and end of treatment. Patients undergo computed tomography (CT) or positron emission tomography (PET) at baseline, cycle 5 and then every 8 weeks. Patients undergo magnetic resonance imaging (MRI) at baseline, cycles 3, 5, and then every 8 weeks.

After completion of study treatment, patients are followed up within 4 weeks and then every 12 weeks thereafter.

Intravenous and Intrathecal Nivolumab in Treating Patients With Leptomeningeal Disease

Phase I/Ib Study of Concurrent Intravenous and Intrathecal Nivolumab for Melanoma and Lung Cancer Patients With Leptomeningeal Disease (LMD)

Safety and tolerability of treatment will be assessed by vital signs, laboratory assessments, adverse events, and serious adverse events for the safety population. Adverse events will be graded by the Common Terminology Criteria for Adverse Events version 4.0. Categorical measures will be summarized using frequencies and percentages while continuous variables will be summarized using mean, standard deviation, median, minimum, and maximum.

The Bayesian modified toxicity probability interval method will be used to find the recommended dose.

The Kaplan-Meier method will be used to estimate the distribution of OS from the start of study treatment, and Cox proportional hazard regression will be used to assess the relationship between OS and various covariates of interest, including but not limited to patient demographics, tumor characteristics, disease characteristics, and the expression of biomarkers.

National Cancer Institute (NCI)

M.D. Anderson Cancer Center

Brain Neoplasms

Brain Diseases

Central Nervous System Diseases

Patients complete a survey related to their perceived quality of care via telephone and have their medical chart reviewed prospectively.

Electronic Health Record Review

Survey Administration

Barbara J O'Brien, MD

This study evaluates patient perceptions around quality of care through telemedicine in neuro-oncology. Studying questionnaires related to perceptions quality of care through telemedicine in patients with brain cancer may help doctors to improve the delivery of care through this modality.

PRIMARY OBJECTIVE:

I. To evaluate the patient-perceived quality of care by group (telemedicine versus in-person visits) in patients with central nervous system (CNS) cancer.

SECONDARY OBJECTIVES:

I. To characterize the visits provided by telemedicine compared to those in-person.

II. To contrast the average time spent on telemedicine visits compared to in-person visits, and the delay between visit order placement and visit occurring.

III. To evaluate the domains of patient care addressed on a telemedicine visit versus in-person visit per documentation, including (1) treatment planning, (2) symptom burden, (3) goals of care.

IV. To evaluate frequency of acute care sought (through emergency room or urgent care clinic) within 30 days of encounter in telemedicine visit versus (vs) in-person visit.

V. The impact of patient and clinical characteristics on perceived quality of care in the context of covariate-adjusted modeling.

OUTLINE:

Patients complete a survey related to their perceived quality of care via telephone and have their medical chart reviewed prospectively.

Patient Perceptions Around Quality of Care Through Telemedicine in Neuro-Oncology

Survey responses will be summarized by ordinal category as counts with percentages, separately by group. Will separately estimate the proportion of each ordinal level of each group with 95% confidence interval.

Will separately estimate the proportion of each ordinal level of each group with 95% confidence interval.

Differences between groups will be assessed by 2-sample 2-sided t-test and Mann-Whitney test, Fisher's exact test, or chi-square test.

Will be summarized by group per mean, median, standard deviation, and range. Differences between groups will be assessed by t-test and Mann-Whitney test.

Will be summarized as counts with percentages by group. Differences between groups will be assessed by chi-square test.

Will be summarized as counts with percentages by group. Differences between groups will be provisionally assessed by Fisher's exact test.

Symptoms and General Pathology

Recurrence

Neoplasms, Glandular and Epithelial

Patients receive glutaminase inhibitor CB-839 hydrochloride PO BID and sapanisertib PO QD on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Sapanisertib

Telaglenastat Hydrochloride

Site Public Contact

Erminia Massarelli

Jorge J. Nieva

Jonathan W. Riess

Paul K. Paik

Jonathan W Riess

This phase I/Ib trial studies the side effects and best dose of CB-839 HCl when given together with sapanisertib in treating patients with non-small cell lung cancer that has spread to other places in the body (advanced). CB-839 HCl and sapanisertib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

PRIMARY OBJECTIVE:

I. To determine the safety and tolerability of glutaminase inhibitor CB-839 hydrochloride (CB-839 HCl) (telaglenastat) in combination with MLN0128 (sapanisertib) and determine the recommended phase 2 dose (RP2D) of the combination.

SECONDARY OBJECTIVES:

I. To observe and record anti-tumor activity. II. To examine preliminary efficacy of CB-839 HCl (telaglenastat) and MLN0128 (sapanisertib) in squamous cell lung cancers (LSCC) and in select, molecularly-defined non-small cell lung cancer (NSCLC) cohorts.

IIa. To evaluate the objective response rate (ORR), progression-free survival (PFS), and disease control rate (DCR) of patients treated with CB-839 HCl (telaglenastat) and MLN0128 (sapanisertib).

EXPLORATORY OBJECTIVES:

I. To correlate genomic and metabolomic signatures with response. II. To evaluate metabolic response (18Glutamine \[GLN\]-positron emission tomography \[PET\]/computed tomography \[CT\]; 18Fluorodeoxyglucose \[FDG\]-PET/CT) in NSCLC tumors treated with CB-839 HCl (telaglenastat) and MLN0128 (sapanisertib) in the dose expansion.

OUTLINE: This is a dose-escalation study of glutaminase inhibitor CB-839 hydrochloride.

Patients receive glutaminase inhibitor CB-839 hydrochloride orally (PO) twice daily (BID) and sapanisertib PO once daily (QD) on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up quarterly.

Testing of the Anti Cancer Drugs CB-839 HCl (Telaglenastat) and MLN0128 (Sapanisertib) in Advanced Stage Non-small Cell Lung Cancer

A Phase 1 Trial of MLN0128 (Sapanisertib) and CB-839 HCl (Telaglenastat) in Advanced NSCLC Patients

NCI is committed to sharing data in accordance with NIH policy. For more details on how clinical trial data is shared, access the link to the NIH data sharing policy page.

Genomic and metabolic signatures will be correlated with responses. Changes in glutamine, glutamate, aspartate, and asparagine will be measured, and responders will be compared to non-responders using a two-sample t-test or Wilcoxon test.

Will be evaluated according to dose-limiting toxicities during cycle 1 graded using National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0.

Response rate will be calculated for each cohort along with an exact 95% confidence interval.

Median PFS will be determined using the Kaplan-Meier method individual for each cohort and for all patients as well.

ORR will be assessed by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria.

Will be evaluated by Kaplan-Meier estimates.

DCR will be assessed by RECIST 1.1 criteria.

Change in tumor uptake of radio-labelled glutamine on PET from baseline to cycle 1 day 8 will be quantified by the standardized uptake value maximum (SUVmax) (a standard PET parameter) in the largest measurable lesion. The before and after 18F-Gln PET values will be compared using log(after/before) as a measure of relative change.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Intravenous and Intrathecal Nivolumab in Treating Patients With Leptomeningeal Disease	NCT03025256	Acral Lentigino... Central Nervous... Clinical Stage ... Leptomeningeal ... Melanocytoma Metastatic Lung... Metastatic Mela... Metastatic Muco... Metastatic Uvea... Stage IV Lung C...	Biospecimen Col... Computed Tomogr... Lumbar Puncture Magnetic Resona... Nivolumab Positron Emissi...	18 Years -	M.D. Anderson Cancer Center
Patient Perceptions Around Quality of Care Through Telemedicine in Neuro-Oncology	NCT04988009	Central Nervous... Leptomeningeal ... Metastatic Mali... Primary Brain N...	Electronic Heal... Survey Administ...	18 Years -	M.D. Anderson Cancer Center
Testing of the Anti Cancer Drugs CB-839 HCl (Telaglenastat) and MLN0128 (Sapanisertib) in Advanced Stage Non-small Cell Lung Cancer	NCT04250545	Leptomeningeal ... Metastatic Lung... Metastatic Mali... Recurrent Lung ... Stage IV Lung C... Stage IVA Lung ... Stage IVB Lung ...	Sapanisertib Telaglenastat H...	18 Years -	National Cancer Institute (NCI)

Spots Global Cancer Trial Database for leptomeningeal neoplasm