Behaviors and Mental Disorders

All Conditions

Neoplasms

Nervous System Diseases

Cognitive Dysfunction

Central Nervous System Neoplasms

Nervous System Neoplasms

Cognition Disorders

Neurocognitive Disorders

Mental Disorders

Psychotic Disorders

Anti-Dyskinesia Agents

All Drugs and Chemicals

Cardiotonic Agents

Memantine

Antiparkinson Agents

Dopamine

Dopamine Agents

Neurotransmitter Agents

Excitatory Amino Acid Antagonists

Patients receive memantine PO BID beginning at the time of study enrollment (no later than 1st day of RT) up to 6 months after completion of standard of care RT in the absence of unacceptable toxicity. Patients also complete CogState cognitive testing at baseline, at completion of RT, and at 3, 6, and 12 months after completion of RT.

Cogstate Assessment Battery

Memantine Hydrochloride

Nadia N. Laack, M.D.

This early phase I trial studies the feasibility of giving memantine for the reduction of cognitive impairment after radiation therapy in pediatric patients with central nervous system tumors. Memantine may reduce the effects of radiation therapy on memory and thinking.

PRIMARY OBJECTIVE:

I. To evaluate the feasibility of twice daily memantine started before radiation therapy (RT) and one month after RT.

SECONDARY OBJECTIVE:

I. To evaluate the feasibility of twice daily (BID) memantine started before RT and continued 3 and 6 months after RT.

EXPLORATORY OBJECTIVES:

I. To evaluate the change in neurocognitive function (NCF) as found by formal neurocognitive testing between baseline and 12 months post-RT.

II. To compare the change in NCF between baseline and the end of RT, 3,and 6 months after RT using both neuropsychological testing and the CogState exam.

III. To evaluate changes in quantitative volumetric brain imaging using Neuroquant software analysis of magnetic resonance imaging (MRI) imaging before and 12 months after radiation.

IV. To correlate cognitive changes detected by CogState composite score and formal neuropsychological testing.

V. Disease-free (of primary tumor) and overall survival.

OUTLINE:

Patients receive memantine orally (PO) BID beginning at the time of study enrollment (no later than 1st day of RT) up to 6 months after completion of standard of care RT in the absence of unacceptable toxicity. Patients also complete CogState cognitive testing at baseline, at completion of RT, and at 3, 6, and 12 months after completion of RT.

After completion of study, patients are followed up periodically.

Memantine for the Reduction of Cognitive Impairment After Radiation Therapy in Pediatric Patients With Central Nervous System Tumors

A Pilot Study Evaluating the Feasibility of Memantine in Reducing Cognitive Impairment in Pediatric Patients After Radiation Therapy for Central Nervous System Tumors

Will be summarized and reported descriptively. This will be assessed using results from neurocognitive testing. Differences between scores from baseline and 12 months post-RT will be calculated, along with corresponding 90% confidence intervals. Change index (reliable change index \[RCI\]) will be calculated as well over this time period. A paired t-test or the Wilcoxon rank-sum test will be used as applicable. Additional analyses concerning change in NCF using additional subscales from the results of neurocognitive testing may be performed, but will be hypothesis generating and considered exploratory. These may include the use of other neurocognitive testing subscales using t-tests or the Wilcoxon rank-sum test, variations of RCI, and linear regression to assess the relationship of each subscale with changes in NCF.

Determined by the CogState composite score. Will be summarized and compared to baseline values. Additional analyses concerning NCF at or between various time points may be performed, but will be hypothesis generating and considered exploratory. These may include comparisons of NCF between baseline and the end of RT, 3 months, and 12 months post-RT. Subscales of the results from the CogState may also be used for these analyses. CogState is a computerized cognitive test that will include the following battery of tests: International Shopping List Test (verbal learning and delayed recall), Detection (processing speed), Identification (attention), One Card Learning (visual memory), and One Back (working memory). Higher scores generally indicate greater NCF.

Determined by neuropsychological examination. Will be summarized and compared to baseline values. Additional analyses concerning change in NCF at or between various time points may be performed, but will be hypothesis generating and considered exploratory. These may include comparisons of NCF between baseline and the end of RT, 3 months, and 12 months post-RT .

Neuroquant Software will be used to analyze quantitative magnetic resonance imaging measurements of changes in hippocampal volume. Differences between measurements will be reported, along with corresponding 90% confidence intervals. A paired t-test or the Wilcoxon rank-sum test will be used as applicable. Additional analyses concerning hippocampal volume may be performed, but will be hypothesis generating and considered exploratory.

Cognitive changes detected by the CogState composite score will be correlated with results from formal neuropsychological testing using Pearson's r or Spearman's rank method, as applicable.

The rate of feasibility (the percentage of patients who attempt to take at least 80% percent of their prescribed dose) will be calculated, along with corresponding 90% confidence intervals.

Mayo Clinic

Symptoms and General Pathology

Rare Diseases

Recurrence

Neuroblastoma

Medulloblastoma

Ganglioneuroblastoma

Rhabdomyosarcoma

Pinealoma

Neoplasms, Germ Cell and Embryonal

Disease Attributes

Neuroectodermal Tumors, Primitive, Peripheral

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Neuroepithelial

Neoplasms by Histologic Type

Neoplasms, Glandular and Epithelial

Neoplasms, Nerve Tissue

Myosarcoma

Neoplasms, Connective and Soft Tissue

Sarcoma

Glioma

Brain Neoplasms

Brain Diseases

Central Nervous System Diseases

Pineoblastoma

Embryonal Tumor With Multilayered Rosettes

Pineocytoma

Neuroepithelioma

Soft Tissue Sarcoma

Antineoplastic Agents

Irinotecan

Camptothecin

Adavosertib

Topoisomerase I Inhibitors

Enzyme Inhibitors

Patients receive irinotecan hydrochloride PO and adavosertib PO on days 1-5. Treatment repeats every 21 days for up to 18 cycles in the absence of disease progression or unacceptable toxicity.

Irinotecan Hydrochloride

Kristina A Cole

This phase I/II trial studies the side effects and best dose of adavosertib and irinotecan hydrochloride in treating younger patients with solid tumors that have come back (relapsed) or that have not responded to standard therapy (refractory). Adavosertib and irinotecan hydrochloride may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

PRIMARY OBJECTIVES:

I. To estimate the maximum tolerated dose (MTD) and/or recommended phase 2 dose of adavosertib (AZD1755 \[MK-1775\]) administered on days 1 through 5 every 21 days, in combination with oral irinotecan (irinotecan hydrochloride), to children with recurrent or refractory solid tumors.

II. To define and describe the toxicities of AZD1755 (MK-1775) in combination with oral irinotecan administered on this schedule.

III. To characterize the pharmacokinetics of AZD1755 (MK-1775) in children with refractory cancer.

SECONDARY OBJECTIVES:

I. To preliminarily define the antitumor activity of AZD1755 (MK-1775) and irinotecan within the confines of a Phase 1 study.

II. To obtain initial phase 2 efficacy data on the anti-tumor activity of AZD1755 (MK-1775) in combination with irinotecan administered to children with relapsed or refractory neuroblastoma, in children with relapsed or refractory medulloblastoma/CNS PNET (central nervous system primitive neuroectodermal tumor) and in children with relapsed or refractory rhabdomyosarcoma.

III. To investigate checkpoint over-ride by AZD1755 (MK-1775) via the mechanism-based pharmacodynamic (PD) biomarker of decreased cyclin-dependent kinase 1 (CDK1) phosphorylation in correlative and exploratory studies.

IV. To evaluate potential predictive biomarkers of AZD1755 (MK-1775) sensitivity, including v-myc avian myelocytomatosis viral oncogene homolog (MYC), v-myc avian myelocytomatosis viral oncogene neuroblastoma derived homolog (MYCN), phosphorylated-WEE1 G2 checkpoint kinase (p-Wee1), enhancer of zeste homolog 2 (Drosophila) (EZH2) and gamma-H2A histone family, member gamma-(H2AX) in tumor tissues in correlative and exploratory studies.

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

Patients receive irinotecan hydrochloride orally (PO) and adavosertib PO on days 1-5. Treatment repeats every 21 days for up to 18 cycles in the absence of disease progression or unacceptable toxicity.

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

Adavosertib and Irinotecan Hydrochloride in Treating Younger Patients With Relapsed or Refractory Solid Tumors

A Phase 1/2 Study of AZD1775 (MK-1775) in Combination With Oral Irinotecan in Children, Adolescents, and Young Adults With Relapsed or Refractory Solid Tumors

MTD is defined as the maximum doses of adavosertib and irinotecan hydrochloride at which fewer than one-third of patients experience dose limiting toxicities when receiving this combination.

To define and describe the toxicities of AZD1755 (MK-1775) in combination with oral irinotecan administered on this schedule.

The PK parameters will be summarized by means and standard deviations

Frequency (%) of response-evaluable patients with best overall response of partial or complete response as determined by revised Response Evaluation Criteria in Solid Tumors (RECIST) guideline (version 1.1).

Mean (SD) of the increase in gamma H2AX at 4 hours versus baseline among patients in Part A stratified by dose level.

Frequency (%) of Part B Neuroblastoma participants with MYCN amplification.

National Cancer Institute (NCI)

Adverse event reporting is collected routinely using case report forms. The SAE table reflects NCI Common Terminology Criteria for Adverse Events (CTCAEs) submitted by the institution via expedited reporting (NCI AdEERs / CAeRs). All remaining CTCAEs collected by means other than expedited reporting are non-serious and are reported in the "AE Other" table. Ineligible patients are excluded from reporting of adverse events. All-Cause Mortality includes all deaths collected on the study.

Patients with relapsed or refractory solid tumors, including patients with primary or metastatic CNS tumors treated at 70 mg/m2 Irinotecan (IRIN) and 50 mg/m2 AZD1775 (MK-1775)

Part A, Dose Level 1

Patients with relapsed or refractory solid tumors, including patients with primary or metastatic CNS tumors treated at 70 mg/m2 Irinotecan (IRIN) and 65 mg/m2 AZD1775 (MK-1775)

Part A, Dose Level 2

Patients with relapsed or refractory solid tumors, including patients with primary or metastatic CNS tumors treated at 90 mg/m2 Irinotecan (IRIN) and 65 mg/m2 AZD1775 (MK-1775)

Part A, Dose Level 3

Patients with relapsed or refractory solid tumors, including patients with primary or metastatic CNS tumors treated at 90 mg/m2 Irinotecan (IRIN) and 85 mg/m2 AZD1775 (MK-1775)

Part A, Dose Level 4

Patients with relapsed or refractory solid tumors, including patients with primary or metastatic CNS tumors treated at 90 mg/m2 Irinotecan (IRIN) and 110 mg/m2 AZD1775 (MK-1775)

Part A, Dose Level 5

Patients with relapsed or refractory solid tumors, including patients with primary or metastatic CNS tumors treated at the MTD/RP2D of 90 mg/m2 Irinotecan (IRIN) and 110 mg/m2 AZD1775 (MK-1775)

Part A, PK Expansion

Patients with relapsed or refractory neuroblastoma treated at the MTD/RP2D of 90 mg/m2 Irinotecan (IRIN) and 85 mg/m2 AZD1775 (MK-1775)

Part B, Neuroblastoma

Patients with relapsed or refractory Medulloblastoma/CNS PNET treated at the MTD/RP2D of 90 mg/m2 Irinotecan (IRIN) and 85 mg/m2 AZD1775 (MK-1775)

Part C, Medulloblastoma/CNS PNET

Patients with relapsed or refractory Rhabdomyosarcoma treated at the MTD/RP2D of 90 mg/m2 Irinotecan (IRIN) and 85 mg/m2 AZD1775 (MK-1775)

Part D, Rhabdomyosarcoma

Total

Age, Categorical

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

Results Reporting Coordinator

Irinotecan (IRIN)

AZD1775 (MK-1775)

Part A Patients with relapsed or refractory solid tumors, including patients with primary or metastatic CNS tumors treated with Irinotecan (IRIN) and AZD1775 (MK-1775)

Part A

All Part A patients contributed to determining MTD. Only Toxicity evaluable patients were accounted.

Maximum Tolerated Dose (MTD)

Number of Participants With Cycle 1 DLT

Patients with relapsed or refractory solid tumors, including patients with primary or metastatic CNS tumors treated at 70 mg/m2 Irinotecan (IRIN) and 50 mg/m2 AZD1775 (MK-1775

Summary statistics for PK parameter for patients in Part A. Per study protocol, PK measures were not required for Parts B, C, or D, therefore, data were not and will not be collected.

Pharmacokinetic (PK) Parameters of Adavosertib in Terms of Systemic Exposure, AUC

Pharmacokinetic (PK) Parameters of Adavosertib in Terms of Systemic Exposure, Cmax

Pharmacokinetic (PK) Parameters of Adavosertib in Terms of Systemic Exposure, HL-Lambda (Half Life)

Pharmacokinetic (PK) Parameters of Adavosertib in Terms of Systemic Exposure, Tmax

Patients with complete response or partial response among response-evaluable patients.

Number and Percentage of Participants With Best Overall Response With Partial or Complete Response

Part A patients with data available. Per study protocol, pharmacodynamics were not required for Parts B, C, or D, therefore, data were not collected and will not be collected.

Mean Fold Change in Gamma H2AX in Peripheral Blood Mono Nuclear Cells

Only Part B eligible patients. Per study protocol, data for Parts A, C, and D were not and will not ever be collected.

Number and Percentage of Part B Neuroblastoma Participants With MYCN Amplification

Overall Study

Skin and Connective Tissue Diseases

Wounds and Injuries

Dermatitis

Ependymoma

Radiodermatitis

Skin Diseases

Radiation Injuries

Germ Cells Tumors

Beginning first day of CSI proton radiation therapy, caregivers apply StrataXRT gel to half of the patient's forehead and one ear and placebo to the other half of the forehead and the other ear BID until the last day of radiation therapy.

Placebo Administration

Questionnaire Administration

Wound Dressing Material

Susan L McGovern

This phase I trial studies the side effects of a silicone topical wound dressing (StrataXRT) and to see how well it works in preventing radiation dermatitis (skin burns and side effects caused by radiation) in pediatric patients undergoing radiation therapy. StrataXRT may help prevent or decrease severe skin rash, pain, itching, skin peeling, and dry skin in pediatric patients undergoing radiation therapy to the brain or spinal cord.

PRIMARY OBJECTIVES:

I. To estimate the safety (defined using the Common Terminology Criteria for Adverse Events \[CTCAE\], version 5.0) of StrataXRT and placebo by assessing gel-associated toxicities among pediatric patients, aged 2-17 undergoing proton cerebrospinal irradiation (CSI) for central nervous system (CNS) tumors.

II. To estimate the efficacy of StrataXRT as a preventative agent for radiation-associated dermatitis among pediatric patients, aged 2-17 undergoing proton CSI for CNS tumors.

SECONDARY OBJECTIVES:

I. To explore the relationship between dosing and the efficacy of StrataXRT. II. To explore the relationship between the use of StrataXRT and parent-reported symptom experience, as measured by the Radiation-Induced Skin Reaction Assessment Scale (RISRAS).

III. To explore compliance with the application of treatment as documented in a study log by participants.

OUTLINE:

Beginning first day of CSI proton radiation therapy, caregivers apply StrataXRT gel to half of the patient's forehead and one ear and placebo to the other half of the forehead and the other ear twice daily (BID) until the last day of radiation therapy.

StrataXRT in Preventing Radiation Dermatitis in Pediatric Patients Undergoing Radiation Therapy to the Brain or Spinal Cord

A Pilot Study of StrataXRT, a Topical Silicone Barrier, to Prevent Auricular Radiation Dermatitis in Pediatric Patients Undergoing Proton Cerebrospinal Radiation Therapy

Graded per Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. Safety will be summarized with standard summary statistics by adverse event (AE), grade, relation, etc. using the CTCAE 5.0. All summaries will be calculated for each control and experimental forehead and ears.

To estimate the efficacy of StrataXRT among pediatric patients.

Will be measured by the Radiation-Induced Skin Reaction Assessment Scale (RISRAS). The RISRAS Radiation-Induced Skin Reaction Assessment Scale will be summarized by control and experimental ears at each time point (baseline, 5 weekly treatment visits, and at treatment completion visit \[last day of radiation therapy\]).

As documented in a study log by participants.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Memantine for the Reduction of Cognitive Impairment After Radiation Therapy in Pediatric Patients With Central Nervous System Tumors	NCT04217694	Malignant Centr... Primary Central...	Cogstate Assess... Memantine Memantine Hydro...	4 Years - 18 Years	Mayo Clinic
Adavosertib and Irinotecan Hydrochloride in Treating Younger Patients With Relapsed or Refractory Solid Tumors	NCT02095132	Central Nervous... Central Nervous... Central Nervous... Embryonal Tumor... Pineoblastoma Primary Central... Recurrent Child... Recurrent Malig... Recurrent Medul... Recurrent Neuro... Recurrent Rhabd... Refractory Mali... Refractory Medu... Refractory Neur... Refractory Rhab...	Adavosertib Irinotecan Hydr...	1 Year - 21 Years	National Cancer Institute (NCI)
StrataXRT in Preventing Radiation Dermatitis in Pediatric Patients Undergoing Radiation Therapy to the Brain or Spinal Cord	NCT03990597	Central Nervous... Ependymoma Glioma Malignant Intra... Medulloblastoma Pineoblastoma Primary Central...	Placebo Adminis... Questionnaire A... Wound Dressing ...	2 Years - 17 Years	M.D. Anderson Cancer Center
Memantine for the Reduction of Cognitive Impairment After Radiation Therapy in Pediatric Patients With Central Nervous System Tumors	NCT04217694	Malignant Centr... Primary Central...	Cogstate Assess... Memantine Memantine Hydro...	4 Years - 18 Years	Mayo Clinic

Spots Global Cancer Trial Database for primary central nervous system neoplasm