Symptoms and General Pathology

All Conditions

Recurrence

This will be a dose escalation study to determine the maximum tolerated dose (MTD) of perifosine alone in recurrent/progressive pediatric tumors. A standard 3+3 dose escalation design will be employed with 3-6 patients at each dose level.

Open label, phase I study of oral perifosine in recurrent/progressive pediatric solid tumors. This will be a dose escalation study to determine the maximum tolerated dose (MTD) of perifosine alone in recurrent/progressive pediatric tumors. A standard 3+3 dose escalation design will be employed with 3-6 patients at each dose level. All patients will receive perifosine at a loading dose on the first day, followed by a maintenance dose to start on day two until progression each patient will be assigned to a dosing group based on one's body surface area (BSA).

perifosine

Ira Dunkel, MD

The purpose of this study is to test whether perifosine- a drug that inhibits the protein AKT, and has had some success in the treatment of adult cancers- is safe and effective in treating cancer. The investigators want to find out what effects, good and/or bad, it has on the patient and the cancer. The investigators are testing different dose schedules of perifosine and the patient will be asked to partake in one of the dose schedules.

Study of Single Agent Perifosine for Recurrent Pediatric Solid Tumors

Phase I Study of Single Agent Perifosine for Recurrent Pediatric Solid Tumors

University of Wisconsin, Madison

Duke University

AEterna Zentaris

Memorial Sloan Kettering Cancer Center

Maria Victoria Preciado, PhD

Maria Victoria Preciado, Ph.D

Background: In Argentina, central nervous system (CNS) solid tumors (19%) and non-CNS solid tumors (25%) account for 44% of pediatric tumors. The new World Health organization (WHO) 2016 classification, which includes genomic characterization, comprises more than 100 CNS tumor entities and subclasses. In children, glial lineage tumors (gliomas) are the most frequent and comprise astrocytomas, ependymomas and oligodendroglioma, while embryonal CNS tumors are a heterogeneous group of WHO grade IV tumors. Pediatric soft tissue tumors (STT) present difficulties for accurate diagnosis since their morphological and immunophenotypic features overlap among the different histological patterns.

The emergence of new molecular techniques has generated a great advance in the field of solid tumors, particularly in the molecular definition of groups of patients. This fact makes tailor-made treatment feasible, according to the biology of the tumor.

In particular, in children, the identification of treatment targets is especially important since it may avoid unnecessary sequel in a growing child. This project allows the articulation between basic and clinical research groups, thus consolidating the objective of basic translational research and generating both clinical and basic knowledge about the pathogenesis of pediatric solid tumors in our country.

Aim: To standardize and implement a comprehensive multi-level molecular strategy, using medium and high complexity techniques, for the detection of molecular alterations in primary pediatric solid tumors (neuroblastoma, rhabdomyosarcoma, Ewing sarcoma family tumors, soft tissue sarcomas and CNS tumors (gliomas and embryonal)), that can be applied to the diagnosis, prognosis and/or use of targeted therapies against molecular targets in order to provide a tailored therapeutic opportunity.

Material and methods: Pediatric cases of solid tumors will be enrolled prospectively. Based on the statistics of the participating centers, 100 samples will be included. From each case, a formalin fixed biopsy will be available and when possible, a fragment will also be preserved at -70ºC. Clinical and follow-up data will be obtained from the clinical records.

The methodological approaches include: 1) Immunohistochemical detection of tumor lineage determinant markers, some of them with predictive value. 2) FISH (fluorescence in situ hybridization) with break-apart strategy for genes involved in recurrent chromosomal translocations and locus-specific design probes for other unbalanced structural chromosomal structural alterations (amplifications and deletions of genes or chromosomal segments). 3) Real time (RT)-polymerase chain reaction (PCR) detection of fusion transcripts resulting from chromosomal translocations. 4) Quantitative polymerase chain reaction (qPCR) and Sanger sequencing analysis of single nucleotide polymorphisms (SNPs) as targets for therapy. 5) Sanger sequencing analysis of fusions, ins/del as a complement to RT-PCR or FISH (fluorescence in situ hybridization), 6) Next Generation Sequencing (NGS) with a specific and customized panel containing all necessary genes to define a tumor´s genomic mutation profile for diagnosis, risk stratification and prognosis of pediatric tumors. However, NGS sequencing will only be applied in those cases which could not be resolved with the previous strategies or cases with poor evolution

Based on the above analyses, an integrated analysis algorithm will be developed according to WHO recommendations, but adapted to the facilities of the institution. Molecular findings will be correlated with clinical and histological data

Molecular Characterization of Genetic Alterations in Pediatric Solid Tumors

Implementation of a Comprehensive Multi-level Molecular Strategy for the Identification of Genetic Alterations in Pediatric Solid Tumors Aimed at Achieving a Personalized Approach to the Patient

Perform molecular identification of genetic alterations in neuroblastoma, rhabdomyosarcoma, Ewing sarcoma family tumors, soft tissue sarcomas and CNS tumors (gliomas and embryonal)

1) Perform immunohistochemical analysis of tumor lineage determinant markers some of them with predictive value

2) Perform FISH (fluorescence in situ hybridization) analysis of recurrent chromosomal translocations and structural chromosomal alterations

3) Perform RT-qPCR analysis for gene translocations and qPCR analysis for reported SNPs

4) Perform complementary Sanger sequencing analysis for SNPs and translocations of unresolved cases

5) Perform Next Generation Sequencing (NGS) with a specific and customized panel to define a tumor genomic mutation profile important in the diagnosis, risk stratification and prognosis

National Council of Scientific and Technical Research, Argentina

Director of Multidisciplinary Institute for Research of Pediatric Pathologies

Neoplasms

Eye Diseases

Gland and Hormone Related Diseases

Rare Diseases

Retinoblastoma

Sarcoma

Osteosarcoma

Neuroblastoma

Sarcoma, Ewing

Rhabdomyosarcoma

Adrenal Cortex Neoplasms

Soft Tissue Sarcoma

Ewing Sarcoma

Hematinics

All Drugs and Chemicals

Liver Extracts

Sara M. Federico, MD

This study will prospectively characterize the molecular, cellular and genetic properties of primary and metastatic neuroblastoma, osteosarcoma, retinoblastoma, Ewing sarcoma family of tumors, soft tissue sarcomas, adrenocortical tumors and liver malignancies. These cell isolates will be used for gene expression array analysis, genomic analysis by \[SNP\] single nucleotide polymorphism chip, array \[CGH\] comparative genomic hybridization and next generation sequencing, and \[TEM\] transmission electron microscopy analysis. Additionally cell lines and orthotopic xenografts will be created from the obtained tumor specimens.

The specificity of TCRs will be examined by comparing paired TCR from peripheral blood and tumor infiltrating CD4+ and CD8+ T cells. Epigenetic studies will be performed looking at the methylation profile of these cells and to investigate the anti-tumor T cell response both pre- and post-PD1 inhibition.

Each year approximately 2,200 children in the United States are diagnosed with neuroblastoma, osteosarcoma, Ewing sarcoma family of tumors (ESFT), retinoblastoma, soft tissue sarcomas, adrenocortical tumors and liver malignancies. These aggressive pediatric solid tumors are developmental tumors that initiate during periods of tissue growth and morphogenesis in the neural crest, bone and soft tissues. The overall survival rate of these tumors in the advanced stage is less than 30%. Despite intensive efforts over the past three decades using multiple therapeutic modalities including chemotherapy, surgery, radiation, autologous bone marrow transplant and biological agents there has been modest improvement in the long-term survival of these advanced stage pediatric solid tumors. A better understanding of the molecular, cellular and genetic changes that occur in the developing tissues as tumors form could improve the treatment of these devastating cancers. In particular, chemotherapeutic agents may be more effectively targeted to key regulatory enzymes or proteins if the study had a better understanding of the pathways that are disrupted as cells progress from preneoplastic lesions to metastatic disease. The specific aim of this proposal is to identify the changes in gene expression that occur in neuroblastoma, retinoblastoma, osteosarcoma, Ewing sarcoma family of tumors \[ESFT\] and soft tissue sarcoma cells and to correlate these changes with genetic and cellular changes in the tumor cells. \[RNA\] ribonucleic acid and genomic \[DNA\] deoxyribonucleic acid will be isolated from neuroblastoma, retinoblastoma, osteosarcoma, ESFT \[Ewing sarcoma family of tumors\] and soft tissue sarcomas (both primary and metastatic lesions) following surgery or bone marrow aspiration of previously untreated patients. Additional testing will be conducted on tumor samples at any point during or following therapy in which a surgical specimen is obtained. When there is sufficient tumor sample remaining after pathological analysis and banking, fresh primary tumor cells will be used to prepare orthotopic xenografts and to establish models of each disease that recapitulate the advanced forms of neuroblastoma, osteosarcoma, Ewing sarcoma family of tumors \[ESFT\], retinoblastoma and soft tissue sarcomas. For a small group of these excess samples, this study will perform fixation for electron microscopy and process the samples for \[TEM\] transmission electron microscopy analysis. These studies will complement our active research program characterizing the molecular, cellular and genetic features of genetically engineered mouse models of each of these diseases. Biological samples from the cohort of patients treated at St. Jude Children's Research Hospital will be complemented with samples collected and processed by collaborating institutions around the world. Samples collected from international collaborators will be used for analysis of \[DNA\] deoxyribonucleic acid and \[RNA\] ribonucleic acid to complement the St. Jude Children's Research Hospital cohort. Through this collaboration the study anticipates that they will be able to obtain enough fresh tumor samples to improve their understanding of multistage tumorigenesis in pediatric solid malignancies.

Tumor tissue - Tumor tissue will be obtained from patients with a diagnosis of neuroblastoma, retinoblastoma, osteosarcoma, Ewing sarcoma or soft tissue sarcoma at some or all of the following time points: initial biopsy, primary tumor resection, time of disease recurrence. Whole blood - 5 ml of whole blood will be collected from each patient and be used as a matched control. Bone marrow aspiration - 5ml of bone marrow will be taken at the time a patient is having a bone marrow aspirate performed and processed to remove only tumor cells.

Molecular Analysis Of Solid Tumors

Alex's Lemonade Stand Foundation

St. Jude Children's Research Hospital

Antineoplastic Agents

Herbal and Botanical

Irinotecan

Sorafenib

Topoisomerase I Inhibitors

Enzyme Inhibitors

Protein Kinase Inhibitors

Cranberry

* Sorafenib is an oral drug which will be administered on an outpatient basis twice a day continuously (every day of a 21-day cycle) at approximately the same times each day. For patients unable to swallow whole pills, an oral suspension may be prepared with tablets.
* Irinotecan will be administered orally (mixed with "cranberry" type juice) on an outpatient basis once a day on Days 1-5 of a 21-day cycle. Irinotecan should be given at least 1 hour after sorafenib.

Alok Kothari, M.D.

This study proposes to treat patients with the combination of sorafenib and irinotecan. Patients with relapsed, recurrent, refractory, or high risk malignancies whose tumors possess a non-synonymous mutation in Raf, PDGFR, VEGFR, Flt-3, KIT, JAK, STAT, RAS, MEK, or ERK 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 (sorafenib and irinotecan) 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 the targeted agent and/or increase tumor susceptibility to the targeted agent, resulting in increased anti-tumor activity.

Treating Relapsed/Recurrent/Refractory Pediatric Solid Tumors With Sorafenib in Combination With Irinotecan

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

* The percentage of patients who have complete response (CR) and partial response (PR)
* CR: Disappearance of all target lesions. Any pathological lymph nodes must have reduction in short axis to \<10mm. Disappearance of all target lesions and normalization of tumor marker levels.

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).

Washington University School of Medicine

Endostatins

Angiogenesis Inhibitors

Growth Inhibitors

Given by continuous infustion for 28 days (one of two dosing groups) for a total of 2 cycles. Treatment can be extended if tolerated well.

rhEndostatin

Mark W Kieran, MD,PhD

The purpose of this study is to assess the safety of rhEndostatin, to determine how much of the drug stays in the patients blood (pharmacokinetics), to assess the development of proteins in the blood that are produced by the body (antibodies)using rhEndostatin, to determine the effect of rhEndostatin on the formation of new blood vessel factors, and to perform an analysis of the effect of rhEndostatin on circulating endothelial precursor cells (cells in the body that help the tumor build more blood vessels).

* Patients will receive rhEndostatin intravenously continuously for 28 days and will be enrolled into one of 2 dosing groups.
* During the initial course of treatment, subjects will be evaluated for treatment-related side effects. If there are no side effects or disease progression, they may receive an additional 28 days of continuous rhEndostatin.
* During the infusion of rhEndostatin, blood samples will be collected before, during and after the drug is given to determine how much of the drug stays in the blood. Blood will be drawn on days 1, 8, 22 and 29. After the completion of therapy, a blood sample will be collected at least 3 days after to determine the level (if any) of rhEndostatin still in the patients blood.
* Blood and/or urine samples to determine immune reactions against rhEndostatin as well as molecules that tumors may use to stimulate new blood vessel growth will be drawn at the start of the study as well as after the completion of each 28-day cycle and completion of the study.
* When a tumor-specific marker that can be used to monitor the status of the disease is present, blood samples for the measurement marker will be obtained at the start of the study as well as after each cycle.
* Appropriate imaging studies (MRI, CT scan, x-ray) will be done after the completion of the first two 28-day cycles and then at the completion of each 28-day cycle for the duration of therapy.
* Treatment will be continued for 1 year and may be extended if the drugs are well tolerated and disease progression has not occured.

rhEndostatin Protein Involving Pediatric Patients With Cancer

A Phase I, Safety, Pharmacokinetic and Pharmacodynamic Study of rhEndostatin Protein Administered by Continuous Intravenous Infusion to Pediatric Patients With Cancer

Boston Children's Hospital

Dana-Farber Cancer Institute

Mark Kieran, MD, PhD

Carboplatin

IV, Infusion, AUC2 mg/ml.min, Once every 21 days, until progression or unacceptable toxicity

IV, Infusion, 12 (9) mg/m²/day, Once daily x 10 days, every 21 days, until progression or unacceptable toxicity

IV, Infusion, 10 (18) mg/m²/day, Once daily x 10 days, every 21 days, until progression or unacceptable toxicity

Bristol-Myers Squibb

The purpose of this study is to determine the long term safety of patients with refractory solid tumors who have experienced clinical benefit after at least 6 cycles of treatment in BMS Protocol CA124-001 or CA124-002.

A Study to Document Long-Term Safety and Continued Benefit of Irinotecan and Carboplatin or Irinotecan in Subjects With Refractory Solid Tumors (Rollover Study -001, -002)

A Study to Document Long-term Safety and Continued Benefit of Irinotecan and Carboplatin or Irinotecan in Subjects 1 - 21 Years of Age With Refractory Solid Tumors Who Have Experienced Clinical Benefit Following a Minimum of 6 Cycles of Therapy on BMS Protocol CA124-001 or BMS Protocol CA124-002

Study Director

Blood and Lymph Conditions

Carcinoma

Thrombocytopenia

Male and female patients aged 1-21 years with a primary solid tumor undergoing treatment with the pre-defined chemotherapy regimens of EFT, MAP or D9803.

Participants will receive weekly doses of romiplostim, beginning with cycle 4. The initial romiplostim dose will be 10 mcg/kg, and subsequent doses w ill vary based on chemotherapy regimen for a target of platelet count \> 75,000- 200,000/mcL. Participants will continue romiplostim until completion of MAP or D9803, as defined above. Maximum romiplostim dose is 10 mcg/kg. Participants will be followed until 6 months after the last dose of romiplostim.

Romiplostim

Michael Ortiz, MD

The purpose of this study is to find out whether romiplostim can help prevent low platelet counts caused by N8 or EFT chemotherapy, reduce the number of platelet transfusions required during chemotherapy, and prevent treatment delays due to low platelet counts.

A Study of Romiplostim to Prevent Low Platelet Counts in Children and Young Adults Receiving Chemotherapy for Solid Tumors

A Single Arm Open-Label Pilot Study of Prophylactic Romiplostim Use Compared to Benchmark Rate in the Prevention of Chemotherapy Induced Thrombocytopenia in Pediatric Solid Tumors Patients Undergoing Myelosuppressive Chemotherapy

Memorial Sloan Kettering Cancer Center supports the international committee of medical journal editors (ICMJE) and the ethical obligation of responsible sharing of data from clinical trials. The protocol summary, a statistical summary, and informed consent form will be made available on clinicaltrials.gov when required as a condition of Federal awards, other agreements supporting the research and/or as otherwise required. Requests for deidentified individual participant data can be made beginning 12 months after publication and for up to 36 months post publication. Deidentified individual participant data reported in the manuscript will be shared under the terms of a Data Use Agreement and may only be used for approved proposals. Requests may be made to: crdatashare@mskcc.org.

The primary purpose of this study is to evaluate whether romiplostim administration can decrease the total number of platelet transfusions required during the treatment courses of EFT or D9803 when compared to the benchmark rate.

Pediatric Participants

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

United States

Region of Enrollment

Dr. Michael Ortiz MD

Total Number of Platelet Transfusions During the Studied Portions of the EFT or D9803 Cycles

Overall Study

Anti-Infective Agents

Sirolimus

Temsirolimus

MTOR Inhibitors

Immunosuppressive Agents

Immunologic Factors

Anti-Bacterial Agents

Antibiotics, Antitubercular

Clotrimazole

Miconazole

Antifungal Agents

This is a single arm, phase I study. Eligible patients will receive a loading dose of oral perifosine on the first day, followed by a maintenance dose starting on the second day until progression. Each patient is assigned to a group according to their body surface area (BSA). Temsirolimus will be combined with perifosine at four dose levels to determine the MTD for the combination therapy. Temsirolimus dosing will start on the same day as the perifosine load.

The patient will take oral tablets of perifosine at a dose and frequency to be determined their height, weight and time when they enter the study as those entering early will be treated with lower dose levels (dosing frequency will vary from once a week to daily). The patient will receive an intravenous injection of temsirolimus once a week at a dose to be determined by their height, weight and time when they enter the study as those entering early will be treated with lower doses. In addition they will be asked to keep a medicine diary.

perifosine + temsirolimus

The purpose of this study is to test the safety and effectiveness of 2 drugs, perifosine in combination with temsirolimus in children with solid tumors. Neither drug is currently part of the standard treatment of solid tumors in children. Both drugs have been tested alone to treat solid tumors in children with little success. There is now new insight that if given together, perifosine and temsirolimus may work together to stop the growth of solid tumors and may also make them shrink. The doctor wants to find out what effects; good and/or bad, perifosine in combination with temsirolimus has on the patient and the cancer. The doctors are testing four different dose schedules of perifosine with temsirolimus and the patient will be asked to partake in one of the dose schedules. The dose schedule will be lower for those enrolled early in the study.

Perifosine With Temsirolimus for Recurrent Pediatric Solid Tumors

Phase I Study of Perifosine With Temsirolimus for Recurrent Pediatric Solid Tumors

NATL COMP CA NETWORK

Pfizer

Natacha ENTZ-WERLE, MD, PhD

Juliette SIMON, MD

Eric GUERIN, MD

Sarah JANNIER, MD

Damien REITA, MD

Véronique LINDNER, MD

Noelle WEINGERTNER, MD

Benoit LHERMITTE, MD

Pediatric solid tumors with an unfavorable prognosis remain a public health issue due to their morbidity and mortality and their rapidly evolving profile. They are defined by an expected overall survival of \< 30%. Progress has been made in genomic medicine with existing recommendations for the adult population, with the objective of personalized medicine. Recommendations for the pediatric population are still under consideration

Clinical and Therapeutic Impact of Large Genomic Studies at Diagnosis in Pediatric Solid Cancers

Evaluation of the Clinical and Therapeutic Impact of Large Genomic Studies at Diagnosis in Pediatric Solid Cancers

The aim of this retrospective study is to improve and harmonize international practices

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Study of Single Agent Perifosine for Recurrent Pediatric Solid Tumors	NCT00776867	Solid Tumors	perifosine	- 21 Years	Memorial Sloan Kettering Cancer Center
Molecular Characterization of Genetic Alterations in Pediatric Solid Tumors	NCT04773808	Pediatric Solid...		- 18 Years	National Council of Scientific and Technical Research, Argentina
Molecular Analysis Of Solid Tumors	NCT01050296	Pediatric Solid...		- 25 Years	St. Jude Children's Research Hospital
Molecular Analysis Of Solid Tumors	NCT01050296	Pediatric Solid...		- 25 Years	St. Jude Children's Research Hospital
Treating Relapsed/Recurrent/Refractory Pediatric Solid Tumors With Sorafenib in Combination With Irinotecan	NCT02747537	Pediatric Solid...	Sorafenib Irinotecan	24 Months - 21 Years	Washington University School of Medicine
Study of Single Agent Perifosine for Recurrent Pediatric Solid Tumors	NCT00776867	Solid Tumors	perifosine	- 21 Years	Memorial Sloan Kettering Cancer Center
rhEndostatin Protein Involving Pediatric Patients With Cancer	NCT00165373	Solid Tumors	rhEndostatin	2 Years - 18 Years	Dana-Farber Cancer Institute
A Study to Document Long-Term Safety and Continued Benefit of Irinotecan and Carboplatin or Irinotecan in Subjects With Refractory Solid Tumors (Rollover Study -001, -002)	NCT00990912	Pediatric Solid...	Carboplatin Irinotecan Irinotecan	1 Year - 18 Years	Bristol-Myers Squibb
A Study of Romiplostim to Prevent Low Platelet Counts in Children and Young Adults Receiving Chemotherapy for Solid Tumors	NCT04671901	Solid Tumor Solid Tumor, Ch... Solid Carcinoma	Romiplostim	1 Year - 21 Years	Memorial Sloan Kettering Cancer Center
Study of Single Agent Perifosine for Recurrent Pediatric Solid Tumors	NCT00776867	Solid Tumors	perifosine	- 21 Years	Memorial Sloan Kettering Cancer Center
Perifosine With Temsirolimus for Recurrent Pediatric Solid Tumors	NCT01049841	Pediatric Solid...	perifosine + te...	- 21 Years	Memorial Sloan Kettering Cancer Center
Clinical and Therapeutic Impact of Large Genomic Studies at Diagnosis in Pediatric Solid Cancers	NCT06171971	Pediatric Solid...		1 Year - 22 Years	University Hospital, Strasbourg, France
Molecular Characterization of Genetic Alterations in Pediatric Solid Tumors	NCT04773808	Pediatric Solid...		- 18 Years	National Council of Scientific and Technical Research, Argentina

Spots Global Cancer Trial Database for pediatric solid tumors