Symptoms and General Pathology

All Conditions

Neoplasms

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Gland and Hormone Related Diseases

Nervous System Diseases

Diseases and Abnormalities at or Before Birth

Respiratory Tract (Lung and Bronchial) Diseases

Rare Diseases

Syndrome

Ovarian Neoplasms

Sarcoma

Pituitary Diseases

Goiter

Wilms Tumor

Pituitary Neoplasms

Rhabdomyosarcoma

Rhabdomyosarcoma, Embryonal

Leydig Cell Tumor

Pulmonary Blastoma

Sertoli-Leydig Cell Tumor

Pinealoma

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Connective and Soft Tissue

Neoplasms by Histologic Type

Hypothalamic Diseases

Brain Diseases

Central Nervous System Diseases

Endocrine System Diseases

Myosarcoma

Kidney Neoplasms

Urologic Neoplasms

Urogenital Neoplasms

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

Endocrine Gland Neoplasms

Hypothalamic Neoplasms

Supratentorial Neoplasms

Brain Neoplasms

Central Nervous System Neoplasms

Nervous System Neoplasms

Neoplasms, Neuroepithelial

Neoplasms, Germ Cell and Embryonal

Neoplasms, Glandular and Epithelial

Neoplasms, Nerve Tissue

Lung Neoplasms

Respiratory Tract Neoplasms

Thoracic Neoplasms

Sex Cord-Gonadal Stromal Tumors

Testicular Neoplasms

Genital Neoplasms, Male

Genital Diseases

Genital Diseases, Male

Testicular Diseases

Gonadal Disorders

Ovarian Diseases

Adnexal Diseases

Genital Diseases, Female

Genital Neoplasms, Female

Ovarian Cancer

Soft Tissue Sarcoma

Wilms' Tumor

Pineoblastoma

Rhabdomyosarcoma Embryonal

Pleuropulmonary Blastoma

Sertoli-leydig Cell Tumors

Pineocytoma

Neuroepithelioma

D. Ashley Hill, MD

Kris Ann Schultz, MD

Pleuropulmonary Blastoma (PPB) is a rare lung tumor which develops in childhood. The underlying genetic factors which contribute to the development and progression of PPB are not defined. We are working to identify the genetic factors which may contribute to the development of this rare tumor.

Studies of inherited cancer syndromes have provided unique opportunities to uncover and explain important cellular pathways with broad relevance to both sporadic cancers and human development. This proposal studies the cancer predisposition syndrome originally described as a familial form of pleuropulmonary blastoma (PPB). PPB is a rare, aggressive lung cancer that affects young children. Children with PPB and/or their family members are at increased risk for a number of rare conditions, including Wilms tumor, rhabdomyosarcoma, brain tumors, ovarian tumors and nodular hyperplasia of the thyroid gland. In 2009, we mapped a PPB locus and identified germline, loss of function mutations in one copy of DICER1 as the genetic basis of this syndrome. DICER1 encodes a protein that performs the final critical step in maturation of microRNAs (miRNAs). miRNAs are an important form of gene regulation. The syndrome's varied nature is likely attributable to the various roles of miRNAs during different developmental and/or functional circumstances. This study focuses on defining the full phenotype of this cancer predisposition syndrome including penetrance, expressivity in children and adults, pathologic classification of disease and spectrum of predisposing DICER1 mutations. Improved understanding of the clinical and genetic features of this cancer predisposition syndrome is essential to facilitate early diagnosis when the diseases are most curable, and to create genetic counseling and educational materials to guide medical care.

We are collecting blood samples or saliva samples. When available, we also collect tumor samples from prior surgical procedures.

Elucidating the Genetic Basis of the Pleuropulmonary Blastoma (PPB) Familial Cancer Syndrome

Sequence data deposited in ClinVar upon publication. Publication of all final results in NIHMS

Ashley Hill

MD, Professor of Pathology

Medulloblastoma

Neuroblastoma

Rhabdoid Tumor

Neuroectodermal Tumors, Primitive, Peripheral

Glioma

Embryonal Tumor With Multilayered Rosettes

Anti-Infective Agents

Antineoplastic Agents

All Drugs and Chemicals

Amino Acids

Eflornithine

Antiprotozoal Agents

Antiparasitic Agents

Enzyme Inhibitors

Ornithine

In this study subjects without CNS disease will receive oral difluoromethylornithine (DFMO) at a dose of 500 to 1000 mg/m2 BID

Subjects with CNS disease will receive a dose of 2500 mg/m2/dose BID in order to facilitate crossing into the CNS.

eflornithine HCl

Genevieve Bergendahl, MSN

Suzanne Treadway

Valerie Brown, MD

Giselle Sholler, MD

To provide DFMO in an expanded use setting to subjects with relapsed rare tumors with increased LIN28 expression or MYCN amplification or up regulation of ornithine decarboxylase.

An Intermediate Expanded Use Trial of DFMO

K C Pharmaceuticals Inc.

USWM, LLC

Giselle Sholler

Study Chair

Musculoskeletal Diseases

Glioblastoma

Astrocytoma

Craniopharyngioma

Adamantinoma

Oligodendroglioma

Gliosarcoma

Ganglioglioma

Neurocytoma

Brain Tumor, Childhood

Anaplastic Astrocytoma

Anaplastic Oligodendroglioma

Pilocytic Astrocytoma

Antineoplaston therapy (Atengenal + Astugenal) by IV infusion every four hours for at least 12 months. Study subjects receive increasing dosages of Atengenal and Astugenal until the maximum tolerated dose is reached.

Children with a brain tumor will receive Antineoplaston therapy (Atengenal + Astugenal).

Antineoplaston therapy (Atengenal + Astugenal)

Stanislaw R. Burzynski, MD, PhD

RATIONALE: Current therapies for childhood brain tumors provide limited benefit to the patient. The anti-cancer properties of Antineoplaston therapy suggest that it may prove beneficial in the treatment of childhood brain tumors.

PURPOSE: This study is being performed to determine the effects (good and bad) that Antineoplaston therapy has on children (\> 6 months of age) with brain tumors.

OVERVIEW: This is a single arm, open-label study in which children with brain tumors receive gradually escalating doses of intravenous Antineoplaston therapy (Atengenal + Astugenal) until the maximum tolerated dose is reached. Treatment continues for at least 12 months in the absence of disease progression or unacceptable toxicity.

OBJECTIVES:

* To determine the efficacy of Antineoplaston therapy in children with a brain tumor, as measured by an objective response to therapy (complete response, partial response or stable disease).
* To determine the safety and tolerance of Antineoplaston therapy in children with a brain tumor.
* To determine objective response, tumor size is measured utilizing MRI scans, which are performed every 8 weeks for the first two years, every 3 months for the third and fourth years, every 6 months for the 5th and sixth years, and annually thereafter.

PROJECTED ACCRUAL: A total of 20-40 patients will be accrued to this study.

Antineoplaston Therapy in Treating Children With Brain Tumors

Phase II Study of Antineoplastons A10 and AS2-1 in Children With Brain Tumors

Objective response rate per Response Assessment in Neuro-Oncology (RANO) for target lesions and assessed by MRI: Complete Response (CR), disappearance of all disease sustained for at least four weeks; Partial Response (PR), \>=50% decrease in the sum of the products of of the greatest perpendicular diameters of all measurable enhancing lesions, sustained for at least four weeks.

6 months, 12 months, 24 months, 36 months, 48 months, 60 months overall survival

Burzynski Research Institute

Adverse event data was collected through regular patient assessment and regular laboratory testing

Antineoplaston therapy (Atengenal + Astugenal) by IV infusion every four hours for at least 12 months. Study subjects receive increasing dosages of Atengenal and Astugenal until the maximum tolerated dose is reached.

Children with a brain tumor will receive Antineoplaston therapy (Atengenal + Astugenal).

Antineoplaston Therapy

Antineoplaston therapy (Atengenal + Astugenal) by IV infusion every four hours for at least 12 months. Study subjects receive increasing dosages of Atengenal and Astugenal until the maximum tolerated dose is reached.

Antineoplaston therapy (Atengenal + Astugenal): Children with a brain tumor will receive Antineoplaston therapy (Atengenal + Astugenal).

Age, Continuous

Sex: Female, Male

S. R. Burzynski, MD, PhD

Complete Response

Partial Response

Stable Disease

Progressive Disease

Number of Participants With Objective Response

6 months overall survival

12 months overall survival

24 months overall survival

36 months overall survival

48 months overall survival

60 months overall survival

All study subjects receiving any Antineoplaston therapy

Percentage of Participants Who Survived

Overall Study

Recurrence

Disease Attributes

Germ Cells Tumors

Malignant Germ Cell Tumor

Natriuretic Agents

Carboplatin

Melphalan

Mannitol

Sodium thiosulfate

Mechlorethamine

Nitrogen Mustard Compounds

Antidotes

Antineoplastic Agents, Alkylating

Alkylating Agents

Immunosuppressive Agents

Immunologic Factors

Diuretics

Protective Agents

Antioxidants

Antitubercular Agents

Anti-Bacterial Agents

Chelating Agents

Phenylalanine

Alanine

Patients receive mannitol IA over 30 seconds, melphalan IA over 10 minutes, and carboplatin IA over 10 minutes. Patients then receive sodium thiosulfate IV over 15 minutes at 4 and 8 hours after carboplatin. Treatment repeats every 4-6 weeks for up to 12 cycles in the absence of disease progression or unacceptable toxicity.

Quality-of-Life Assessment

Questionnaire Administration

Sodium Thiosulfate

Edward A Neuwelt

This phase I/II trial studies the side effects and best dose of melphalan when given together with carboplatin, mannitol, and sodium thiosulfate, and to see how well they work in treating patients with central nervous system (CNS) embryonal or germ cell tumors that is growing, spreading, or getting worse (progressive) or has come back (recurrent). Drugs used in chemotherapy, such as melphalan and carboplatin, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Osmotic blood-brain barrier disruption (BBBD) uses mannitol to open the blood vessels around the brain and allow cancer-killing substances to be carried directly to the brain. Sodium thiosulfate may help lessen or prevent hearing loss and toxicities in patients undergoing chemotherapy with carboplatin and BBBD. Giving melphalan together with carboplatin, mannitol, and sodium thiosulfate may be an effective treatment for recurrent or progressive CNS embryonal or germ cell tumors.

PRIMARY OBJECTIVES:

I. To determine the maximum tolerated dose (MTD) of intra-arterial (IA) melphalan given with IA carboplatin, osmotic BBBD and delayed intravenous (IV) sodium thiosulfate (STS) in subjects with recurrent or progressive embryonal and germ cell tumors of the CNS. (Phase I) II. To estimate the response rate in subjects with recurrent or progressive CNS embryonal and germ cell tumors treated with IA carboplatin, IA melphalan, osmotic BBBD and delayed IV STS. (Phase II)

SECONDARY OBJECTIVES:

I. To describe 2-year progression-free survival (PFS) and overall survival (OS) rates in subjects with recurrent or progressive CNS embryonal and germ cell tumors treated with IA carboplatin, IA melphalan, osmotic BBBD and delayed IV STS. (Phase II) II. To describe neuropsychological and audiology outcomes in subjects with recurrent or progressive CNS embryonal and germ cell tumors treated with IA carboplatin, IA melphalan, osmotic BBBD and delayed IV STS. (Phase II) III. To describe the overall toxicity of IA carboplatin and IA melphalan in conjunction with osmotic BBBD and delayed STS chemoprotection in subjects with recurrent or progressive CNS embryonal or germ cell tumors. (Phase II)

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

Patients receive mannitol IA over 30 seconds, melphalan IA over 10 minutes, and carboplatin IA over 10 minutes. Patients then receive sodium thiosulfate IV over 15 minutes at 4 and 8 hours after carboplatin. Treatment repeats every 4-6 weeks for up to 12 cycles in the absence of disease progression or unacceptable toxicity.

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

Melphalan, Carboplatin, Mannitol, and Sodium Thiosulfate in Treating Patients With Recurrent or Progressive CNS Embryonal or Germ Cell Tumors

Phase I/II Study of Intra-Arterial Melphalan Given With Intra-Arterial Carboplatin, Osmotic Blood-Brain Barrier Disruption and Delayed Otoprotective Sodium Thiosulfate for Patients With Recurrent or Progressive CNS Embryonal or Germ Cell Tumors

Will be assessed based on the incidence of dose-limiting toxicity, graded using the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0. All toxicities will be tabulated by event and by overall. The toxicities will also be tabulated by highest grade. The recovery from toxicities (i.e. hematologic toxicities) will also be summarized.

Descriptive statistics will be estimated.

Estimation made using Kaplan-Meier product limit estimation. A Cox proportional hazards regression model will be fit to the data to estimate the association of progression free survival and overall survival with baseline demographic and disease characteristics.

Quantitative scores, whenever possible, will be derived from each measure and converted to measure-specific Z scores using normative data. Post-treatment Z scores will be subtracted from pre-treatment Z scores to calculate absolute change in neuropsychological test performance. Significant change will be defined as change of 1 standard deviation. These data will be summarized descriptively.

Will be graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0. Estimated using proportions with associated confidence intervals.

National Institute of Neurological Disorders and Stroke (NINDS)

Oregon Health and Science University

OHSU Knight Cancer Institute

Principal Investigator

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Elucidating the Genetic Basis of the Pleuropulmonary Blastoma (PPB) Familial Cancer Syndrome	NCT00565903	Pleuropulmonary... Cystic Nephroma Sertoli-Leydig ... Medulloepitheli... Embryonal Rhabd... Goiter Sarcoma Pineoblastoma Pituitary Tumor... Wilms Tumor		1 Day - 95 Years	Children's National Research Institute
An Intermediate Expanded Use Trial of DFMO	NCT03581240	Neuroblastoma Medulloblastoma Typical Teratoi... Embryonal Tumor... Ependymoblastom... Medulloepitheli...	eflornithine HC...	0 Years - 30 Years	Milton S. Hershey Medical Center
Antineoplaston Therapy in Treating Children With Brain Tumors	NCT00003458	Childhood Brain...	Antineoplaston ...	6 Months - 18 Years	Burzynski Research Institute
Elucidating the Genetic Basis of the Pleuropulmonary Blastoma (PPB) Familial Cancer Syndrome	NCT00565903	Pleuropulmonary... Cystic Nephroma Sertoli-Leydig ... Medulloepitheli... Embryonal Rhabd... Goiter Sarcoma Pineoblastoma Pituitary Tumor... Wilms Tumor		1 Day - 95 Years	Children's National Research Institute
An Intermediate Expanded Use Trial of DFMO	NCT03581240	Neuroblastoma Medulloblastoma Typical Teratoi... Embryonal Tumor... Ependymoblastom... Medulloepitheli...	eflornithine HC...	0 Years - 30 Years	Milton S. Hershey Medical Center
Melphalan, Carboplatin, Mannitol, and Sodium Thiosulfate in Treating Patients With Recurrent or Progressive CNS Embryonal or Germ Cell Tumors	NCT00983398	Central Nervous... Embryonal Tumor... Germ Cell Tumor Medulloblastoma Medulloepitheli... Primitive Neuro... Recurrent Child... Recurrent Malig... Recurrent Medul... Recurrent Primi...	Carboplatin Mannitol Melphalan Quality-of-Life... Questionnaire A... Sodium Thiosulf...	18 Years - 45 Years	OHSU Knight Cancer Institute
Antineoplaston Therapy in Treating Children With Brain Tumors	NCT00003458	Childhood Brain...	Antineoplaston ...	6 Months - 18 Years	Burzynski Research Institute

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