Symptoms and General Pathology

All Conditions

Neoplasms

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Gland and Hormone Related Diseases

Digestive System Diseases

Eye Diseases

Nervous System Diseases

Diseases and Abnormalities at or Before Birth

Rare Diseases

Recurrence

Ovarian Neoplasms

Carcinoma, Ovarian Epithelial

Carcinoma, Renal Cell

Liver Neoplasms

Glioma

Retinoblastoma

Sarcoma

Teratoma

Brain Neoplasms

Wilms Tumor

Central Nervous System Neoplasms

Medulloblastoma

Neuroblastoma

Sarcoma, Ewing

Testicular Neoplasms

Kidney Neoplasms

Nervous System Neoplasms

Astrocytoma

Ependymoma

Rhabdomyosarcoma

Desmoplastic Small Round Cell Tumor

Hepatoblastoma

Chordoma

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms, Connective and Soft Tissue

Neoplasms by Histologic Type

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Liver Diseases

Neuroectodermal Tumors, Primitive, Peripheral

Neoplasms, Neuroepithelial

Neoplasms, Glandular and Epithelial

Neoplasms, Nerve Tissue

Retinal Neoplasms

Eye Neoplasms

Eye Diseases, Hereditary

Retinal Diseases

Ovarian Cancer

Ovarian Epithelial Cancer

Renal Cell Carcinoma

Soft Tissue Sarcoma

Germ Cells Tumors

Wilms' Tumor

Ewing Sarcoma

Brain Tumor, Adult

Ovarian Germ Cell Tumor

Testicular Germ Cell Tumor

Neuroepithelioma

Malignant Germ Cell Tumor

Extragonadal Germ Cell Tumor

Antineoplastic Agents

All Drugs and Chemicals

Hematinics

Melphalan

Lenograstim

Busulfan

Liver Extracts

Thiotepa

Amifostine

Adjuvants, Immunologic

Immunologic Factors

Antineoplastic Agents, Alkylating

Alkylating Agents

Immunosuppressive Agents

Protective Agents

Radiation-Protective Agents

Patients with solid tumor or brain tumor in the 1-18 years old stratum.

Patients with solid tumor or brain tumor in the 19-45 years old stratum.

Patients receive amifostine intravenous (IV) over 5 minutes beginning 30 minutes prior to melphalan and thiotepa administration on days -5 to -1.

Cohorts of 3-6 patients receive escalating doses of amifostine until the maximum tolerated dose is determined.

amifostine trihydrate

Patients receive oral busulfan every 6 hours on days -8 to -6.

busulfan

All patients receive filgrastim (G-CSF) IV for 1 week.

filgrastim

melphalan intravenous (IV) over 30 minutes on days -5 and -4

melphalan

thiotepa intravenous (IV) over 2 hours on days -3 and -2.

thiotepa

peripheral blood stem cell transplantation (PBSC)

John P. Perentesis, MD

RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining chemotherapy with peripheral stem cell transplantation may allow the doctor to give higher doses of chemotherapy drugs and kill more tumor cells. Chemoprotective drugs such as amifostine may protect normal cells from the side effects of high-dose chemotherapy.

PURPOSE: Phase I trial to study the effectiveness of amifostine in protecting from the side effects of peripheral stem cell transplantation in treating patients who have high-risk or relapsed solid tumors.

OBJECTIVES:

* Determine the dose-limiting toxicity of amifostine chemoprotection with peripheral blood stem cell transplantation plus chemotherapy in patients with high-risk or relapsed solid tumors or brain tumors.
* Determine response or time to disease progression in patients treated with this regimen.

OUTLINE: This is a dose-escalation study of amifostine. Patients are stratified according to age (1 to 18 vs 19 to 45 years).

All patients receive filgrastim (G-CSF) IV for 1 week. On day 6 of G-CSF administration, patients undergo peripheral blood stem cell (PBSC) harvest followed by chemotherapy.

Patients receive oral busulfan every 6 hours on days -8 to -6 followed by melphalan IV over 30 minutes on days -5 and -4 and thiotepa IV over 2 hours on days -3 and -2. Patients receive amifostine IV over 5 minutes beginning 30 minutes prior to melphalan and thiotepa administration on days -5 to -1. PBSC are reinfused on day 0.

Cohorts of 3-6 patients receive escalating doses of amifostine until the maximum tolerated dose is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.

Patients are followed on day 50; at 3, 6, and 9 months; and at 1, 2, and 3 years post PBSC transplantation.

PROJECTED ACCRUAL: A maximum of 60 patients (30 per stratum) will be accrued for this study within 3 years.

Amifostine to Protect From Side Effects of PSCT in Treating Patients With Solid Tumors

A Phase I Study of the Chemoprotectant Amifostine With Autologous Stem Cell Transplantation for High Risk or Relapsed Pediatric Solid Tumors and Brain Tumors

Masonic Cancer Center, University of Minnesota

John Perentesis, MD

Vaccines

Immunomodulating Agents

High dose chemotherapy plus peripheral blood stem cell transplant followed by TTRNA-xALT and TTRNA-DCs.

NMA Salvage chemotherapy plus peripheral blood stem cell transplant followed by TTRNA-xALT and TTRNA-DCs.

TTRNA-xALT 3 x 10\^7/kg by intravenous injection once.

TTRNA-xALT

TTRNA-DCs 1 x 10\^7 by intradermal injection every 2 weeks for 3 total doses.

TTRNA-DCs

Duane Mitchell, MD, PhD

Immunotherapy is a specific approach to treating cancer that has shown promise in adult patients for the treatment of melanoma, malignant brain tumors, and other cancers. The study investigators will use the experience they have gained from these studies to try to improve the outcome for children affected by a recurrent brain tumor.

Approximately 35 patients with first recurrence of medulloblastoma (reMB)/supratentorial primitive neuroectodermal tumors (PNETs) will be treated with tumor-specific immune cells and dendritic cell vaccines to see what impact they have on the tumor.

Malignant brain tumors now represent the most frequent cause of cancer death in children. Despite aggressive and highly toxic multi-modality therapy including surgery, craniospinal radiation, and high-dose chemotherapy coupled with peripheral blood stem cell transplantation, almost half the children diagnosed with the most common malignant brain tumors, medulloblastoma (MB) and primitive neuroectodermal tumors (PNET), will still die from recurrent disease. Furthermore, survivors are often left with severe and lifelong treatment-associated cognitive and motor deficits. The development of more effective and tumor-specific therapies that will not add further toxicity to existing treatments is paramount in improving clinical outcomes for children affected by MB/PNETs. Immunotherapy targeting tumor-specific antigens expressed within brain tumors is a modality potentially capable of meeting this clear and urgent need.

Despite considerable advancements and promising clinical results observed in immunotherapy trials directed against adult malignant brain tumors, efforts in the immunologic treatment of pediatric brain tumors have been limited to relatively few notable studies. This is due, at least in part, to the often limited viable tumor tissue available for tumor cell-based vaccine preparations, and the lack of identification of consistently expressed tumor-specific antigens within these cancers.

The use of total tumor RNA (TTRNA)-loaded dendritic cells (DCs) was pioneered at Duke University, as a novel platform for inducing potent immunologic responses against the variety of uncharacterized and patient-specific antigens present within malignant tumor cells. Duke demonstrated that sufficient RNA for clinical vaccine preparations can be amplified with high fidelity using existing molecular technologies from as few as 500 isolated pediatric and adult brain tumor cells, thus allowing vaccine preparation from surgical biopsies and even microdissected archival tumor specimens.

Immunotherapy administered during recovery from chemotherapy may have tremendous advantages, as adoptive cellular therapy following lymphodepletive conditioning regimens has emerged as the most effective treatment strategy for advanced and refractory melanoma. Our hypothesis is that DC + ex vivo expanded Autologous Lymphocyte Transfer (xALT) therapy targeting recurrent MB/PNETs during recovery from myeloablative chemotherapy will be safe and will prolong survival in children and young adults with recurrent MB/PNETs.

In this study, the investigators will treat patients with first recurrence reMB/PNETs after completion of definitive radiation therapy with autologous tumor-specific T cell immunotherapy (TTRNA-xALT) plus TTRNA-loaded dendritic cell vaccine.

Following surgical resection, biopsy, or cytology examination with confirmatory pathologic diagnosis, patients will be enrolled into Group A (high-dose chemotherapy or HDC) or Group B (non-myeloablative or NMA salvage chemotherapy) based on eligibility for HDC. Patients with localized relapse and have not failed HDC+ peripheral blood stem cell transplant (PBSCT) previously will be enrolled into Group A. Patients with disseminated disease, have previously failed HDC+PBSCT, or are otherwise considered poor candidates for HDC based on overall health status, but otherwise meet eligibility criteria, will be enrolled into Group B. All patients will receive DC + xALT therapy.

Vaccine Immunotherapy for Recurrent Medulloblastoma and Primitive Neuroectodermal Tumor

Recurrent Medulloblastoma and Primitive Neuroectodermal Tumor Adoptive T Cell Therapy During Recover From Myeloablative Chemotherapy and Hematopoietic Stem Cell Transplantation

PFS is defined as time interval from date of first DC vaccine to date of progression (death is also treated as progression) or censoring, whichever happens first.

Radiographic response will be assessed as a percentage change in tumor size from pre-treatment (baseline) MRI scans of the brain and spine obtained with and without contrast. Evaluation will be based on the NCI-endorsed, World Health Organization RECIST criteria and using a modified version of the MacDonald criteria (complete response, partial response, stable disease, progressive disease or not assessible).

Peripheral blood will be used to compare pre-therapy lymphocyte function to defined intervals after each immunization. Blood will be obtained for immunologic monitoring prior to non-mobilized leukapheresis, prior to immunotherapy, 1 day post Vaccine #1, 4 (+/- 1) days post Vaccine #1, weekly post Vaccine #1 for six weeks.

We will measure serum cytokines pre and post therapy. Blood will be obtained for immunologic monitoring prior to non-mobilized leukapheresis, prior to immunotherapy, 1 day post Vaccine #1, 4 (+/- 1) days post Vaccine #1, weekly post Vaccine #1 for six weeks.

We will conduct flow cytometry from patient samples. Blood will be obtained for immunologic monitoring prior to non-mobilized leukapheresis, prior to immunotherapy, 1 day post Vaccine #1, 4 (+/- 1) days post Vaccine #1, weekly post Vaccine #1 for six weeks.

Kaplan-Meier estimator will be used to describe length of overall survival from initiation of vaccine #1 for both Groups A and B.

United States Department of Defense

University of Florida

An "AE" will be defined as any adverse change from the subject's pre-treatment baseline condition, including any clinical or laboratory test abnormality that occurs during the course of research after treatment has started. A summary of recorded AEs will be kept which will categorize the event by organ system, relationship to treatment, its grade of severity, and resolution.

High dose chemotherapy plus peripheral blood stem cell transplant followed by TTRNA-xALT and TTRNA-DCs.

TTRNA-xALT: TTRNA-xALT 3 x 10\^7/kg by intravenous injection once.

TTRNA-DCs: TTRNA-DCs 1 x 10\^7 by intradermal injection every 2 weeks for 3 total doses.

Group A

NMA Salvage chemotherapy plus peripheral blood stem cell transplant followed by TTRNA-xALT and TTRNA-DCs.

TTRNA-xALT: TTRNA-xALT 3 x 10\^7/kg by intravenous injection once.

TTRNA-DCs: TTRNA-DCs 1 x 10\^7 by intradermal injection every 2 weeks for 3 total doses.

Group B

Total

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

United States

Region of Enrollment

Given that number evaluable subjects was below targeted enrollment, this study was underpowered for the desired statistical comparison.

Due to COVID we anticipate that the immunologic secondary endpoints will be completed in 6-12 months or change to exploratory.

Kristine Wynne

Based on published literature, PFS-12 for patients with recurrent disease after initiating treatment with HDC + PBSCT or standard salvage therapy was 33% (95% confidence interval of 10%, 59%). The study was designed to differentiate between a PFS-12 rate of 33% (null hypothesis) and 55% (alternative hypothesis). If 35 patients enrolled, this assessment has 90% power assuming a type I error rate of 0.10. We assume that PFS of historical controls follows exponential distribution.

12 Month Progression-free Survival (PFS-12)

Objective Radiographic Response Rate

Correlate Magnitude and Persistence of Anti-tumor Humoral or Cellular Immunity With Clinical Outcome

Evaluate Changes in Cytokine Profile and Toll-Like Receptor Activation Status

Characterize Immunologic Phenotype of Lymphocyte Subsets and NK Cells

Determine of Overall Survival Rate

Overall Study

Neoplasm Metastasis

Neoplastic Processes

Brain Diseases

Central Nervous System Diseases

Anticonvulsants

Central Nervous System Depressants

Psychotropic Drugs

Etoposide

Etoposide phosphate

Valproic Acid

Enzyme Inhibitors

Neurotransmitter Agents

Valproate Starting Dose of 10 mg/kg By Mouth Daily. Etoposide 25 - 50 mg/m\^2 By Mouth Daily.

Valproate

Tribhawan S Vats, MD

Primary Objective:

* Determine the interindividual range and median of individual maximum tolerated doses of valproic acid administered as one time evening dose in conjunction with a dose oral etoposide (50 mg/m2/day for children, but only 25mg/m2/day for adults to start) for four different age groups.

Secondary Objectives:

* Determine the qualitative and quantitative toxicity and reversibility of toxicity of valproic acid in conjunction with oral etoposide,
* To investigate the clinical pharmacokinetics of valproic acid when given in conjunction with oral etoposide,
* To describe quality of life of patients with relapsed, or progressive central and peripheral nervous system tumors when treated with oral valproic acid and etoposide,
* To observe and describe the response pattern of progressive central nervous system tumors treated with oral valproic acid and etoposide,
* To observe and describe event free survival time and overall survival time of patients with relapsed, or progressive central nervous system tumors when treated with oral valproic acid and etoposide,
* To determine if histone deacetylase activity and topoisomerase expression in lymphocytes of patients is related to valproic acid levels, and
* To determine, if the individual maximal tolerated dose (iMTD) depends on the initial performance status of the patient in the beginning of the treatment.

Study Drugs:

Etoposide is designed to block cell growth by breaking the DNA, which may cause the cells to die.

Valproic acid was first designed as an anti-seizure medication. It was also found to change cancer cells and make them more sensitive to etoposide.

Screening Tests:

Before you start treatment on this study, you will have "screening tests". These tests help your doctor decide if you are eligible to take part in this study.

* Your medical history will be reviewed.
* You will have a physical exam.
* You will be asked how well you are able to perform the normal activities of daily living (performance status evaluation).
* You will complete a questionnaire about your activities or daily living. The questionnaire will take about 5 to 10 minutes to complete.
* Blood (about 2-3 tablespoons) will be drawn for routine tests. This routine blood draw may include a pregnancy test for women who are able to have children. To be eligible to take part in this study, the pregnancy test must be negative.
* Urine may be collected to check for metabolic disease. This urine sample may include a pregnancy test for women who are able to have children. To be eligible to take part in this study, the pregnancy test must be negative.
* You will have a magnetic resonance imaging (MRI) or computed tomography (CT) scan.
* If your doctor thinks it is necessary, you may have additional blood and/or urine tests.

Dose Escalation:

When you begin the study, you will begin receiving the lowest dose level of valproic acid. Every week, the dose will be increased. This will continue until the maximum tolerated dose (MTD) is found. Once the MTD is found, you will continue to receive that dose level of valproic acid while you are on study. However, if your doctor thinks it is necessary, this dose level could be lowered.

If you are a child (less than or equal to 18 years of age), the amount of etoposide that you take while on study will not change.

If you are an adult (more than 18 years of age), your will receive a low dose of etoposide while the MTD of valproic acid is being found. After the MTD of valproic acid is found, your dose of etoposide will be increased every week until the MTD is found. However, if your doctor thinks it is necessary, this dose level could be lowered.

Study Drug Administration:

You will receive valproic acid and etoposide every evening in pill form.

If you have difficulty swallowing the pills, etoposide can be given in the evening in liquid form. Valproic acid can be given in liquid form, divided in 2 doses per day, 1 in the morning and 1 in the evening.

Study Visits During Dose Escalation:

While your valproic acid or etoposide medication is being increased, every week you will have a physical exam and blood (about 2-3 tablespoons)and urine will be collected for routine tests.

Every other month, you will have CT or MRI scans to check the status of the disease. You may have these tests and procedures more often if your doctor thinks it is necessary.

Study Visits After Maximum Tolerated Dose (MTD):

Every month, you will have a physical exam, and blood (about 2-3 tablespoons) and urine will be collected for routine tests.

Every other month, you will have CT or MRI scans to check the status of the disease.

Every 6 months, a portion of the blood or urine collected for routine tests will be used for a pregnancy test for women who are able to have children.

-You may have these tests and procedures more often if your doctor thinks it is necessary.

Length of Study:

You may remain on study for up to 2 years. You will be taken off study if the disease gets worse or intolerable side effects occur.

End-of-Study Visit:

Once you are off study, you will have an end-of-study visit. At this visit, the following tests and procedures will be performed:

* You will have a physical exam.
* Blood (about 2-3 tablespoons) and urine will be collected for routine tests.
* If your doctor thinks it is necessary, you will have a CT or MRI to check the status of the disease.

Follow-Up:

Once you are off study, you will be contacted by telephone once a year to check the status of the disease. The phone call will take 2-3 minutes.

This is an investigational study. Etoposide is FDA approved and commercially available. Valproic acid is FDA approved and commercially available for the treatment of seizures. The use of these drugs together is investigational. Up to 120 patients will take part in this multicenter study. Up to 100 will be enrolled at M. D. Anderson.

Valproate and Etoposide for Patients With Neuronal Tumors and Brain Metastases

Valproate (Valproic Acid) and Etoposide for Patients With Progressive, Relapsed or Refractory Neuronal Tumors and Brain Metastases

M.D. Anderson Cancer Center

Skin and Connective Tissue Diseases

Osteosarcoma

Neoplasms, Bone Tissue

Neoplasms, Connective Tissue

Myosarcoma

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

Amino Acids

Temozolomide

Erlotinib Hydrochloride

Tyrosine Kinase Inhibitors

Protein Kinase Inhibitors

Tyrosine

* Erlotinib is an oral drug that will be administered on an outpatient basis at a dose of 85 mg/m\^2/dose once a day continuously (every day of a 28-day cycle)
* Temozolomide is an oral drug that will be administered on an outpatient basis at a dose of 180mg/m2/dose once a day on Days 1-5 of a 28-day cycle.

Erlotinib

Alok Kothari, M.D.

This study proposes to treat patients with the combination of erlotinib and temozolomide. Patients with relapsed, recurrent, refractory, or high risk malignancies whose tumors possess a non-synonymous mutation in EGFR, ERBB2, or JAK2V617F (JAK2) will be eligible for the study. Very few phase 2 clinical trials have been performed in pediatrics using targeted agents in combination with conventional chemotherapy agents. Furthermore, since some combinations such as the combination of this study (erlotinib and temozolomide) have shown additive/synergistic effects in preclinical studies, therapy selecting for those patients who possess mutations targeted by the TKI of the study, may unveil activity that has not been previously observed. Thus, the investigators hope to determine whether the addition of additive/synergistic chemotherapy will increase efficacy of target agent and/or increase tumor susceptibility to targeted agent resulting in increased anti-tumor activity.

Erlotinib in Combination With Temozolomide in Treating Relapsed/Recurrent/Refractory Pediatric Solid Tumors

Phase 2 Clinical Trial Treating Relapsed/Recurrent/Refractory Pediatric Solid Tumors With the Genomically-Targeted Agent Erlotinib in Combination With Temozolomide

* The overall response rate is the proportion of patients who have complete response or partial response
* Complete Response (CR): Disappearance of all target lesions, non-target lesions, and normalization of tumor marker level
* Partial Response (PR): At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters.

--Progressive Disease (PD): At least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. (Note: the appearance of one or more new lesions is also considered progressions).

-The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for all toxicity reporting.

Washington University School of Medicine

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Amifostine to Protect From Side Effects of PSCT in Treating Patients With Solid Tumors	NCT00003926	Brain and Centr... Childhood Germ ... Chordoma Kidney Cancer Liver Cancer Neuroblastoma Ovarian Cancer Retinoblastoma Sarcoma	amifostine trih... busulfan filgrastim melphalan thiotepa peripheral bloo...	1 Year - 45 Years	Masonic Cancer Center, University of Minnesota
Amifostine to Protect From Side Effects of PSCT in Treating Patients With Solid Tumors	NCT00003926	Brain and Centr... Childhood Germ ... Chordoma Kidney Cancer Liver Cancer Neuroblastoma Ovarian Cancer Retinoblastoma Sarcoma	amifostine trih... busulfan filgrastim melphalan thiotepa peripheral bloo...	1 Year - 45 Years	Masonic Cancer Center, University of Minnesota
Vaccine Immunotherapy for Recurrent Medulloblastoma and Primitive Neuroectodermal Tumor	NCT01326104	Medulloblastoma Neuroectodermal...	TTRNA-xALT TTRNA-DCs	- 30 Years	University of Florida
Vaccine Immunotherapy for Recurrent Medulloblastoma and Primitive Neuroectodermal Tumor	NCT01326104	Medulloblastoma Neuroectodermal...	TTRNA-xALT TTRNA-DCs	- 30 Years	University of Florida
Valproate and Etoposide for Patients With Neuronal Tumors and Brain Metastases	NCT00513162	Neuroectodermal... Brain Metastase... Advanced Cancer	Valproate Etoposide	-	M.D. Anderson Cancer Center
Erlotinib in Combination With Temozolomide in Treating Relapsed/Recurrent/Refractory Pediatric Solid Tumors	NCT02689336	Glioma Rhabdomyosarcom... Osteosarcoma Medulloblastoma Neuroectodermal... Ependymoma Ewing's Sarcoma Wilms Tumor	Erlotinib Temozolomide	1 Year - 21 Years	Washington University School of Medicine
Vaccine Immunotherapy for Recurrent Medulloblastoma and Primitive Neuroectodermal Tumor	NCT01326104	Medulloblastoma Neuroectodermal...	TTRNA-xALT TTRNA-DCs	- 30 Years	University of Florida
Vaccine Immunotherapy for Recurrent Medulloblastoma and Primitive Neuroectodermal Tumor	NCT01326104	Medulloblastoma Neuroectodermal...	TTRNA-xALT TTRNA-DCs	- 30 Years	University of Florida
Erlotinib in Combination With Temozolomide in Treating Relapsed/Recurrent/Refractory Pediatric Solid Tumors	NCT02689336	Glioma Rhabdomyosarcom... Osteosarcoma Medulloblastoma Neuroectodermal... Ependymoma Ewing's Sarcoma Wilms Tumor	Erlotinib Temozolomide	1 Year - 21 Years	Washington University School of Medicine

Spots Global Cancer Trial Database for neuroectodermal tumor