Neoplasms

All Conditions

Eye Diseases

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Diseases and Abnormalities at or Before Birth

Skin and Connective Tissue Diseases

Symptoms and General Pathology

Rare Diseases

Glioma

Osteosarcoma

Sarcoma

Retinoblastoma

Wilms Tumor

Medulloblastoma

Sarcoma, Ewing

Ependymoma

Rhabdomyosarcoma

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neuroectodermal Tumors, Primitive, Peripheral

Neoplasms, Connective and Soft Tissue

Neoplasms by Histologic Type

Neoplasms, Neuroepithelial

Neoplasms, Germ Cell and Embryonal

Neoplasms, Glandular and Epithelial

Neoplasms, Nerve Tissue

Neoplasms, Bone Tissue

Neoplasms, Connective Tissue

Myosarcoma

Kidney Neoplasms

Urologic Neoplasms

Urogenital Neoplasms

Syndrome

Neoplastic Syndromes, Hereditary

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Kidney Diseases

Urologic Diseases

Male Urogenital Diseases

Genetic Diseases, Inborn

Retinal Neoplasms

Eye Neoplasms

Eye Diseases, Hereditary

Retinal Diseases

Soft Tissue Sarcoma

Wilms' Tumor

Ewing Sarcoma

Neuroepithelioma

Anti-Infective Agents

Antineoplastic Agents

All Drugs and Chemicals

Antirheumatic Agents

Thalidomide

Cyclophosphamide

Angiogenesis Inhibitors

Immunosuppressive Agents

Immunologic Factors

Antineoplastic Agents, Alkylating

Alkylating Agents

Anti-Bacterial Agents

Growth Inhibitors

Cyclophosphamide will be given PO once daily at 2.5 mg/kg/day for children \< 40kg or 100 mg daily for children \> 40kg beginning Day + 30 (30 days post transplant) and continue until at least Day +86

Thalidomide will be initiated at 3mg/kg PO daily beginning Day + 30 (30 days post transplant) and continue until Day +86

Metronomic Cyclophosphamide

Andrew Cluster, M.D.

The purpose of this research study is to determine whether taking either of two low dose drugs that would prevent new blood vessels from growing after stem cell transplant is feasible, and what the side effects of taking each of these drugs after autologous transplant might be. The reason the investigators are looking at these drugs is because one of the things that allows tumors to grow quickly is their ability to stimulate the growth of new blood vessels. By suppressing the growth of new blood vessels after stem cell transplant, the investigators hope to prevent the tumors from coming back or continuing to grow.

Anti-Angiogenic Therapy Post Transplant (ASCR) for Pediatric Solid Tumors

Anti-Angiogenic Therapy After Autologous Stem Cell Rescue (ASCR) for Pediatric Solid Tumors

Assessed by Response Evaluation Criteria in Solid Tumors (RECIST) guideline version 1.1.

Washington University School of Medicine

Nervous System Diseases

Brain Neoplasms

Central Nervous System Neoplasms

Nervous System Neoplasms

Brain Diseases

Central Nervous System Diseases

Etoposide

Carboplatin

Melphalan

Cisplatin

Etoposide phosphate

Thiotepa

Enzyme Inhibitors

Etoposide, carboplatin, melphalan, cisplatin, thiotepa

Chantal Kalifa, MD

Agnès Laplanche, MD

The purpose of this study is to evaluate the efficacy of the combination of surgery, conventional chemotherapy, sequential high-dose chemotherapy with peripheral blood stem cell transplantation and reduced dose radiation therapy in high-risk PNET brain tumors.

High Risk Primitive Neuroectodermal (PNET) Brain Tumors in Childhood

Treatment Protocol for High-Risk PNET Brain Tumors in Children With Surgery, Sequential Chemotherapy, Conventional and High-Dose With Peripheral Blood Stem Cell Transplantation and Radiation Therapy

Gustave Roussy, Cancer Campus, Grand Paris

Recurrence

Glioblastoma

Meningioma

Pinealoma

Astrocytoma

Oligodendroglioma

Rhabdoid Tumor

Gliosarcoma

Choroid Plexus Neoplasms

Neoplasms, Vascular Tissue

Meningeal Neoplasms

Cerebral Ventricle Neoplasms

Pineocytoma

Anaplastic Astrocytoma

Anaplastic Oligodendroglioma

Diffuse Astrocytoma

Pilocytic Astrocytoma

Pleomorphic Xanthoastrocytoma

Gliomatosis Cerebri

Anaplastic Pleomorphic Xanthoastrocytoma

ONC206 is a member of the imipridone class of anti-cancer small molecules that share a unique tri-heterocyclic core chemical structure and target G protein-coupled receptors.

ONC206

Chris Tedesco

Marion Morrison, MD

Referrals

Kelly Mentges, RN

Mark Gilbert, MD

The primary objective of this Phase 1, open-label, dose-escalation, and exploratory study is to evaluate the safety and tolerability profile (establish the maximum-tolerated dose) and evaluate the occurrence of dose-limiting toxicities (DLTs) following single weekly or multiple-day weekly dose regimens of single-agent, oral ONC206 in patients with recurrent, primary central nervous system (CNS) neoplasms.

This is a Phase I, open-label, dose-escalation, and exploratory study of ONC206 in patients with recurrent, primary CNS neoplasms. All patients will be informed about the study and potential risks and required to provide written informed consent prior to undergoing study-related procedures.

There will be a total of 11 Dose Levels. Dose-escalation for Dose Levels 1 through 5 proceeded according to standard 3+3 design using a 28-day DLT window. The first cohort of 3 patients enrolled into the study received Dose Level 1 followed by increments as per the modified Fibonacci sequence. It is anticipated that approximately 46 patients will be enrolled in order to determine the MTD of ONC206.

For Dose Levels 1 through 5, a safety evaluation was conducted when 3 evaluable patients have completed 1 cycle (28 days) of therapy. After Protocol Amendment 6, all available PK data will also be considered for dose escalation decisions. Dose levels may be adjusted based on review of PK data but will not exceed maximum dose levels described in Table 6. Additionally, dose frequencies (e.g., once daily or 3 times daily) may be added and/or removed based on emerging PK data and concentration projections.

Prior to advancing/changing dose levels, a cohort summary must be completed and submitted to the sponsor Medical Monitor, for review and approval. Dose escalation for subsequent patients will proceed as follows:

* If no DLT is reported at a dose level, that dose level will be considered safe, and patient(s) will be enrolled at the next dose level. Toxicity information will continue to be evaluated from the time of the first protocol specific intervention, until 30 days from the last dose of study drug.
* If 1 patient in a cohort of 1 experiences a DLT, the dose level will be expanded to obtain an additional 2 evaluable patients.
* If 1 patient in a cohort at a dose level experiences a DLT, the dose level will be expanded to obtain an additional 3 evaluable patients.
* If 2 of 3 patients in a cohort at a dose level experience a DLT, that dose level will not be considered safe, no further dose escalation will take place, and the MTD will have been exceeded\*.
* If 1 patient experiences a DLT among the expanded cohort of evaluable patients, a cohort of 3 patients will be enrolled in the next higher dose level.
* If 2 or more patients experience a DLT among the expanded cohort of evaluable patients, that dose level will not be considered safe, no further dose escalation will take place, and the MTD will have been exceeded\*. The previous dose level at which ≤1 patients experienced a DLT will be declared the MTD.

  * When the MTD has been exceeded:

If less than 6 patients have been treated in the next lower dose level (the possible MTD level), additional patients will be entered into this dose level until there are 6 patients treated. If ≤1 of these 6 patients encountered DLT, then this dose level will be declared to be the MTD. If 2 or more of the 6 patients encounter DLT, then the MTD has been exceeded.

Given the experience with ONC201, it is possible a MTD may not be reached through the planned dose escalation cohorts. If the therapeutic target concentrations have been achieved in the dose escalation cohorts, and no DLT has been identified, then analysis of the safety and PK data will be evaluated by the Investigators and the Sponsor. Further dose levels may then be considered at higher intermittent dosing schedules and will be added by protocol amendment with review by the Institutional Review Board (IRB) before implementation.

Toxicities will be graded using the Common Terminology Criteria for Adverse Events Version 24.0 (CTCAE 24.0). If the CTCAE 24.0 does not apply to an adverse event, it will be graded as mild, moderate, or severe.

DLTs will be assessed during the first course of each cohort (28 days), and refers to a study drug related or possibly related event that meets 1 of the following criteria using the NCI CTCAE version 5.0:

* Grade 3 or higher non-hematologic toxicity.
* Grade 4 hematologic toxicity (ANC \<0.5 × 109/L and platelet count \<25 × 109/L). Lymphopenia is not considered a DLT. A confirmed DLT requires 2 consecutive measurements separated by 48 hours.
* Grade 3 neutropenia (ANC \<1.0 × 109/L) with elevated fever (\>101°F). A confirmed DLT requires 2 consecutive measurements.
* Grade 3 thrombocytopenia with clinically significant bleeding.
* Inability to receive the scheduled Cycle 2, Day 1 dose of study drug within 14 days due to study drug-related toxicity persisting from Cycle 1 or study drug-related toxicity newly encountered on Day 1 of Cycle 2.

Safety and tolerability will be monitored by assessing physical examinations including height (at Screening only) and weight, KPS, vital signs, ECG, laboratory assessments including hematology, chemistry, and coagulation, as well as collecting of the AEs at every visit.

Phase I Study of Oral ONC206 in Recurrent and Rare Primary Central Nervous System Neoplasms

A First-in-human Phase I Single-agent Dose-escalation, Food Effect and Dose Expansion Study of Oral ONC206 in Recurrent and Rare Primary Central Nervous System Neoplasms

MTD was determined by testing increasing doses up to 200 mg twice daily for 3 successive days a week.

MTD reflects the highest dose of drug that did not cause a Dose-Limiting Toxicity (DLT) in \>33% of participants. DLTs will be assessed in the first course of each cohort (28 days), and refer to a study drug-related or possibly related event that meets 1 of the following criteria defined in the subsequent Primary Outcome Measure using the National Cancer Institute Common Terminology Criteria for Adverse Events Version 5.0 (NCI CTCAE 5.0).

DLTs will be assessed in the first course of each cohort (28 days), and refer to a study drug-related or possibly related event that meets 1 of the following criteria using NCI CTCAE 5.0:

* Grade 3 or higher non-hematologic toxicity.
* Grade 4 hematologic toxicity (ANC \<0.5 × 109/L and platelet count \<25 × 109/L). Lymphopenia is not considered a DLT. A confirmed DLT requires 2 consecutive measurements separated by 48 hours.
* Grade 3 neutropenia (absolute neutrophil count \[ANC\] \<1.0 × 109/L) with elevated fever (\>101°F). A confirmed DLT requires 2 consecutive measurements.
* Grade 3 thrombocytopenia with clinically significant bleeding.
* Inability to receive the scheduled Cycle 2, Day 1 dose of study drug within 14 days due to study drug-related toxicity persisting from Cycle 1 or study drug-related toxicity newly encountered on Day 1 of Cycle 2.

National Institutes of Health (NIH)

Chimerix

Ear, Nose, and Throat Diseases

Digestive System Diseases

Hearing Loss

Deafness

Liver Neoplasms

Hearing Disorders

Ear Diseases

Otorhinolaryngologic Diseases

Sensation Disorders

Neurologic Manifestations

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Liver Diseases

Respiratory System Agents

Acetylcysteine

N-monoacetylcystine

Antiviral Agents

Expectorants

Antioxidants

Protective Agents

Antidotes

This is a dose-finding study using a traditional 3+3 dose escalation scheme. Up to 18 subjects (3 dose levels as per below) will be enrolled to determine the maximum tolerated dose (MTD). The MTD is defined as per traditional 3+3 criteria of less than or equal to one dose-limiting toxicity at the dose level. Once the MTD is determined, subjects will be equally distributed at the "safe" dose levels (less than or equal to the MTD) to determine the optimum dose to achieve NAC levels in the blood necessary for hearing protection.

As of August 2018: The dose-escalation phase was completed and dose-level three was selected for expansion in 9 subjects.

Subjects who are ineligible to receive the study drug NAC will have the option to enroll for study assessments only including laboratory testing and hearing assessments identical to the experimental intervention arm. This is a "cohort of convenience" for which we anticipate up to 36 children will be enrolled over the course of the study.

NAC will be administered intravenously over \~60 minutes starting 4 hours following completion of cisplatin chemotherapy.

Three dose levels have been pre-determined:

Dose Level 1: 225 mg/kg Dose Level 2: 300 mg/kg Dose Level 3: 450 mg/kg

Should Dose Level 3 exceed the MTD, the study will examine blood levels of NAC and if below the target blood level necessary for hearing protection, the study will "de-escalate" from Dose Level 3 to an intermediate Dose Level 2.5 and test a dose of 375 mg/kg.

As of August 2018: Dose escalation completed with MTD not reached. Dose level 3 (450mg/kg) selected for expansion with NAC.

N-Acetylcysteine

Etan Orgel, MD MS

Cisplatin is a key chemotherapy agent for the treatment of multiple childhood cancers but causes permanent hearing loss. This study investigates the drug N-acetylcysteine (NAC) to determine the dose necessary to protect hearing and also how well tolerated NAC is when combined with chemotherapy.

The study is a dose-finding study of N-acetylcysteine (NAC) to protect hearing in children receiving cisplatin for the treatment of their cancer. NAC also has potential to protect the kidneys from cisplatin toxicity.

The study uses a 3+3 dose-escalation scheme to determine the dose of NAC necessary to achieve serum levels consistent with hearing protection in pre-clinical animal models. Three dose levels are predefined. Once the maximum tolerated dose is determined, an expansion cohort will then be enrolled to further evaluate tolerability as well as intra-patient and inter-patient variability in achieved serum levels. An option to enroll in a separate arm for study assessments only is available for those who do not wish to receive NAC. Hearing loss in the cohort will be assessed in the entire cohort in comparison to historical and non-treated children to evaluate for trends toward efficacy.

NAC to Prevent Cisplatin-induced Hearing Loss

A Dose-Finding Study of N-Acetylcysteine (NAC) to Prevent Cisplatin-induced Hearing Loss in Children With Cancer

Following the first dose of cisplatin, NAC will be administered as described below. A NAC level will then be measured immediately following this first dose of NAC to determine if the blood (serum) level reaches the threshold necessary for hearing protection.

Subjects will be monitored during and after each NAC infusion to determine how well they tolerate the drug. Infusion rate related and spontaneously resolving "anaphylactoid" reactions are the most common reported toxicity and will be closely monitored. Most subjects will receive 3 cycles of cisplatin and NAC, typically within the first 15 weeks of starting chemotherapy. Subjects who continue to receive cisplatin and NAC for additional cycles will continue to be monitored.

A NAC serum level will be measured surrounding the first dose of NAC at 4 times:

1. pre-cisplatin (baseline)
2. following cisplatin/before NAC
3. immediately following NAC (primary aim)
4. delayed four hours following NAC

For those in the non-intervention arm, NAC serum levels will be measured at corresponding times as determined by the start of the cisplatin infusion.

Routinely performed hearing assessments will be analyzed at the end of therapy as compared to a historical cohort, non-treated, and to patient's baseline (if available) to evaluate for any trend toward a protective effect from NAC.

Information regarding renal toxicity due to cisplatin will be collected at end of therapy and compared to historical rates and non-treated patients to evaluate a potential protective effect by NAC

Early indicators of tumor response to cisplatin-based chemotherapy (e.g. percent necrosis in resected tumors, early remission rates, etc) will be informally evaluated in comparison to historical data for any evidence NAC decreases efficacy of the chemotherapy

Saliva/cheek swabs will be collected one-time for genotype analysis to examine the influence of glutathione polymorphisms on cisplatin-induced hearing loss and NAC hearing protection

Glutathione serum levels will be measured at times corresponding to NAC levels surrounding the first dose of NAC at 4 times:

1. pre-cisplatin (baseline)
2. following cisplatin/before NAC
3. immediately following NAC (primary aim)
4. delayed four hours following NAC

For those in the non-intervention arm, serum levels will again be measured at corresponding times as determined by the start of the cisplatin infusion.

Children's Hospital Los Angeles

Assistant Professor of Clinical Pediatrics

Blood and Lymph Conditions

Immune System Diseases

Neuroblastoma

Lymphoma

Hodgkin Disease

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

Lymphosarcoma

Hodgkin Lymphoma

Germ Cells Tumors

Medulloblastoma, Childhood

Herbal and Botanical

Estrogens

Genistein

Protein Kinase Inhibitors

Phytoestrogens

Hormones

Hormone Antagonists

Soy Bean

Genistein daily throughout chemotherapy cycles 1 and 2, and placebo daily during chemotherapy cycles 3 and 4

Placebo daily throughout chemotherapy cycles 1 and 2, and genistein daily during chemotherapy cycles 3 and 4

Estrogen-like compound (isoflavone) derived from soybeans

Placebo

William C. Petersen, Jr., M.D.

Toxicities related to pediatric cancer treatment can lead to significant illness, organ damage, treatment delays, increased health care cost, and decrease in quality of life. Such toxicities are largely due to tissue damage sustained by chemotherapy, and strategies designed to limit such cellular damage to normal tissues may reduce therapy-related morbidity and mortality. In addition to their in vitro and in vivo anti-cancer effects, naturally occurring soy isoflavones have anti-inflammatory and anti-oxidant properties, and have been shown to reduce side effects of therapy in adult oncology clinical trials. This study will examine the effect of genistein, the major isoflavone component in soybeans and the most extensively studied of the soy isoflavones, on short-term side effects of myelosuppressive chemotherapy in pediatric cancer patients. Subjects will be randomized to receive either: a) 30 mg genistein daily throughout chemotherapy Cycles 1 and 2 and placebo during chemotherapy Cycles 3 and 4; or b) placebo daily during chemotherapy Cycles 1 and 2 and 30 mg genistein daily during chemotherapy Cycles 3 and 4. Investigators hypothesize that subjects will have fewer short-term therapy-related side effects during cycles of chemotherapy given in conjunction with genistein supplementation than cycles given with placebo.

This is a multi-center, randomized, double blind, placebo-controlled crossover study to evaluate the effect of soy isoflavones on the short term untoward effects of myelosuppressive chemotherapy used to treat pediatric cancers. Newly diagnosed cancer patients aged 1-21 years will be registered to the study and informed consent will be obtained prior to any study-related procedures. Stratification will be based on length of chemotherapy cycles, between 14 day and 21 day cycles. Within strata registered subjects will be randomized 1:1 to one of two schedules:

Arm A: Subjects will receive genistein daily throughout chemotherapy cycles 1 and 2, and placebo during chemotherapy cycles 3 and 4

Arm B: Subjects will receive placebo daily throughout chemotherapy cycles 1 and 2, and genistein during chemotherapy cycles 3 and 4

Subjects will be assessed for safety and efficacy during each cycle with clinical labs, cytokine panels, and physical exams. Drug compliance will be monitored by use of a patient diary as well as monitoring of serum genistein levels. Adverse events will be monitored starting on Cycle 1 Day 1 through 30 days following the last day of protocol therapy (genistein/placebo).

Study of Genistein in Pediatric Oncology Patients (UVA-Gen001)

A Randomized, Placebo-Controlled Pilot Study of Genistein Supplementation in Pediatric Cancer Patients Receiving Myelosuppressive Chemotherapy

This includes hearing loss/tinnitus, motor neuropathy, oral mucositis

University of Virginia

Director, Pediatric Novel Therapeutics Program (Hematology/Oncology)

Genistein daily throughout chemotherapy cycles 1 and 2, and placebo daily during chemotherapy cycles 3 and 4

Genistein: Estrogen-like compound (isoflavone) derived from soybeans

Placebo: Pill that contains no medicine

Arm A: Genistein Followed by Placebo - GENISTEIN Cycles

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Anti-Angiogenic Therapy Post Transplant (ASCR) for Pediatric Solid Tumors	NCT01661400	Glioma Neuroectodermal... Wilms Tumor Rhabdomyosarcom... Sarcoma, Ewing Osteosarcoma Retinoblastoma	Metronomic Cycl... Thalidomide	6 Months - 21 Years	Washington University School of Medicine
High Risk Primitive Neuroectodermal (PNET) Brain Tumors in Childhood	NCT00180791	Medulloblastoma Brain Tumors Neuroectodermal...	Etoposide, carb...	- 10 Years	Gustave Roussy, Cancer Campus, Grand Paris
Phase I Study of Oral ONC206 in Recurrent and Rare Primary Central Nervous System Neoplasms	NCT04541082	Central Nervous... Glioblastoma Gliosarcoma, Ad... Anaplastic Olig... Anaplastic Astr... Pilocytic Astro... Oligodendroglio... Gliomatosis Cer... Pleomorphic Xan... Anaplastic Pleo... Diffuse Midline... Ependymoma Ependymoma, Ana... Medulloblastoma Teratoid Rhabdo... Neuroectodermal... Neuroectodermal... Anaplastic Meni... Atypical Mening... Choroid Plexus ... Pineal Tumor Diffuse Astrocy... Glial Tumor	ONC206	18 Years -	Chimerix
NAC to Prevent Cisplatin-induced Hearing Loss	NCT02094625	Neuroectodermal... Liver Neoplasms Osteosarcoma Other Childhood...	N-Acetylcystein...	1 Year - 21 Years	Children's Hospital Los Angeles
Study of Genistein in Pediatric Oncology Patients (UVA-Gen001)	NCT02624388	Lymphoma Childhood Lymph... Solid Tumor Childhood Solid... Neuroblastoma Ewing Sarcoma Hodgkin Lymphom... Non-Hodgkin Lym... Rhabdomyosarcom... Soft Tissue Sar... Medulloblastoma Germ Cell Tumor Wilms Tumor Brain Neoplasms Medulloblastoma... Neuroectodermal...	Genistein Placebo	1 Year - 21 Years	University of Virginia
Phase I/II: Decitabine/Vaccine Therapy in Relapsed/Refractory Pediatric High Grade Gliomas/Medulloblastomas/CNS PNETs	NCT02332889	Gliomas Medulloblastoma Neuroectodermal...	Vaccine (autolo... Decitabine and ...	2 Years - 25 Years	University of Louisville
Phase I/II: Decitabine/Vaccine Therapy in Relapsed/Refractory Pediatric High Grade Gliomas/Medulloblastomas/CNS PNETs	NCT02332889	Gliomas Medulloblastoma Neuroectodermal...	Vaccine (autolo... Decitabine and ...	2 Years - 25 Years	University of Louisville

Spots Global Cancer Trial Database for neuroectodermal tumors, primitive