Symptoms and General Pathology

All Conditions

Neoplasms

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Diseases and Abnormalities at or Before Birth

Nervous System Diseases

Skin and Connective Tissue Diseases

Rare Diseases

Recurrence

Wilms Tumor

Nerve Sheath Neoplasms

Neurofibrosarcoma

Rhabdoid Tumor

Neoplasms by Histologic Type

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

Neoplasms, Nerve Tissue

Nervous System Neoplasms

Peripheral Nervous System Neoplasms

Peripheral Nervous System Diseases

Neuromuscular Diseases

Fibrosarcoma

Neoplasms, Fibrous Tissue

Neoplasms, Connective Tissue

Neoplasms, Connective and Soft Tissue

Sarcoma

Neurofibromatoses

Neurofibroma

Wilms' Tumor

Malignant Peripheral Nerve Sheath Tumor

Soft Tissue Sarcoma

Neurofibromatosis

Participants will have any type of Wilms tumor or nephroblastoma

Participants will have any Rhabdoid tumor

Participants will have progressive, relapsed, unresectable or metastatic MPNST

Participants must not qualify for Cohorts A, B, or C but have a solid tumor (no hematologic malignancies including lymphoma) for which there is specific evidence that this particular patient's tumor may benefit from selinexor.

This phase II study will initially treat all patients, including adult patients, at the pediatric Selinexor RP2D of 35 mg/m2 (no maximum dose) once weekly using a liquid suspension .

Selinexor

Michael Ortiz, MD

Julia Glade Bender, MD

Rachana Shah, MD

Thomas Cash, MD

Elizabeth Mullen, MD

James Geller, MD

The purpose of this study is to find out whether selinexor is an effective treatment for people under the age of 51 who have a relapsed/refractory Wilms tumor, rhabdoid tumor, MPNST, or another solid tumor that makes a higher than normal amount of XPO1 or has genetic changes that increase the activity of XP01.

A Study of Selinexor in People With Wilms Tumors and Other Solid Tumors

A Multi-Center Phase II Study of Selinexor in Treating Recurrent or Refractory Wilms Tumor and Other Pediatric Solid Tumors

• 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.

To define the antitumor activity of Selinexor in relapsed and refractory Wilms tumor by measuring the Overall Response Rate, defined as Complete Response + Partical Response

Memorial Sloan Kettering Cancer Center

Blood and Lymph Conditions

Immune System Diseases

Digestive System Diseases

Heart and Blood Diseases

Leukemia

Precursor Cell Lymphoblastic Leukemia-Lymphoma

Leukemia, Lymphoid

Hepatic Veno-Occlusive Disease

Lymphoma

Hematologic Diseases

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

Liver Diseases

Gastrointestinal Diseases

Vascular Diseases

Acute Lymphoblastic Leukemia

Lymphoblastic Lymphoma

Acute Graft Versus Host Disease

Hepatic Veno-occlusive Disease

Lymphosarcoma

Antineoplastic Agents

All Drugs and Chemicals

Antimitotic Agents

Pateints treated for a nephrobalstoma or ALL in childhood or adolescence

Drawing blood to realize a genetic analysis for susceptibility to hepatic VOD.

Blood test for genetic analysis

Denise Jolivot, MD

Sybille Lazareff, CRA

Anne Lutun, MD

Liana Carausu, MD

Claire Briandet, MD

Hélène Sudour-Bonnange, MD

Arnauld Verschuur, MD

Caroline Thomas, MD

Joy Benabida, MD

Lauriane Lemelle, MD

Virginie Gandemer, MD

Yves Reguerre, MD

Pascale Blouin, MD

Dominique Valteau-Couanet, MD

Isabelle Pellier, MD

Hepatic veno-occlusive diseases (VOD) during cancer treatment in children are serious toxicities that have occurred with interruptions of chemotherapy and risk of relapse. In addition, these toxicities have a negative impact on the patient's quality of life, serious long-term sequelae and are potentially fatal in children.

The risk factors associated with the occurrence of these complications are, to date, unknown, at the exception to the exposition to certain treatments (6-thioguanine, busulfan, actinomycin D, radiotherapy, etc.). To understand the effects of this toxicity and those of susceptibility to the disease becomes a major issue in the treatment of these children.

Case-control study, nested in two French multicenter cohorts, on pharmacognenetic, biological and clinical susceptibility factors associated with the occurrence of hepatic veno-occlusive disease during the anticancer treatment for nephroblastoma or acute lymphoblastic leukemia, with centralized genetic analysis.

After obtaining consent (patient or parents for minor patients), a blood sample is collected during the routine follow-up consultation and tubes are sent directly to Paris for the pharmacogenetic analysis at the end of the study.

Pharmacogenetic Study of Antimitotic Therapies Involved in Hepatic VOD in Children With Nephroblastoma or ALL

Pharmacogenetic Study of Antimitotic Therapies Involved in Hepatic Veno-occlusive Disease in Children With Nephroblastoma or Acute Lymphoblastic Leukemia

Illumina's "Human Omni2.5-8 v1.3" microarrays explore more than 2,600,000 genetic variants, thus covering the entire genome with more than 300,000 genetic biomarkers in exons.

Age, sociodemographics, personal and cancer history.

University Hospital, Angers

Thrombosis

Embolism

Embolism and Thrombosis

Herbal and Botanical

Kava

Children with nephroblastoma with vena cava thrombosis +/- atrial extension, cared between 1999 and 2019 in Parisian hospitals: Necker and Bicêtre.

Sabine Sarnacki, MD, PhD

Luca Pio, MD

Nephroblastoma (Wilms tumor) is the most common kidney tumor in children. It is a malignant embryonic tumor with a good prognosis with more than 85% long-term survival with appropriate chemotherapy, surgery (which most often consists of a total nephrectomy) and radiotherapy for locally invasive forms. Some nephroblastomas (approximately 10%) present with vascular extension with vena cava thrombus, a situation which may worsen the prognosis due to the complexity of the surgery. While the oncological treatment of nephroblastoma is highly formalized, to date there is no specific guideline on the surgical management of this rare clinical presentation of nephroblastomas.

The aim of the study is to provide recommendations for the surgical management of nephroblastomas with vena cava thrombus in a large multicenter series.

Nephroblastoma (Wilms tumor) is the most common kidney tumor in children. It is a malignant embryonic tumor with a good prognosis with more than 85% long-term survival with appropriate chemotherapy, surgery (which most often consists of a total nephrectomy) and radiotherapy for locally invasive forms. Some nephroblastomas (approximately 10%) present with vascular extension with vena cava thrombus, a situation which may worsen the prognosis due to the complexity of the surgery. While the oncological treatment of nephroblastoma is highly formalized, to date there is no specific guideline on the surgical management of this rare clinical presentation of nephroblastomas.

The management of children with nephroblastomas with vena cava thrombosis is very specific because of the vital risks to diagnosis, especially pulmonary embolism but also cardiac arrest (in the event of extension in the right atrium) and Cerebrovascular accidents by embolism, rarer. Surgery of the primary tumor and its intravascular extension is complex and may require the use of extracorporeal circulation, a source of significant morbidity and even mortality. These patients who will actually have a single kidney are at high risk for renal failure due to possible contralateral kidney damage during surgery. Surgery is not clearly codified because cases are rare, including in expert centers.

The aim of the study is to provide recommendations for the surgical management of nephroblastomas with vena cava thrombus in a large multicenter series.

Vascular Thrombus Involvement in Nephroblastoma

Nephroblastoma With Vena Cava Thrombosis : Multicenter Study Over 20 Years - Analysis of Key Elements of Surgical Management

Study of the medical file. Local or metastatic recurrence.

Study of the medical file. Determination of surgical management recommendations based on survival, the occurrence of local or metastatic recurrence and the study of medical care of the patient.

Study of the medical file. Description of intraoperative complications and Dindo-Clavien classification (classification that defines and grades operative complications in 10 grades).

Study of the medical file. Description of post-operative complications and Dindo-Clavien classification (classification that defines and grades operative complications in 10 grades).

Study of the medical file. Sequelae linked to the toxicity of chemotherapy, radiotherapy and surgery.

Study of the medical file. Identify the oncological and / or surgical prognostic risk factors depending on the medical treatment received.

Assistance Publique - Hôpitaux de Paris

Body Weight

Initially and after pre-operative chemotherapy To evaluate the differences in ADC values according to the malignancy degree of nephroblastoma in children

MRI DWI sequence (ADC values)

Evelina f Nazarova

Galina f Tereshchenko, PhD

Initially, or after preoperative chemotherapy, patients with a kidney tumor are examined on 3T MR scanner or 1.5T MR scanner. A standard MRI study of the abdomen with contrast enhancement is performed. DWI (diffusion weighted) images are included in the standard investigation package and consist of diffusion maps. Then, using Philips workstation (ISP 9.0, Philips, Netherlands), DWI mapping and ADC values collection (mm2/s) are performed. The placement of region of interest (ROI) is selected in the kidney mass in a solid and cystic area with a size up to 100 mm2.

After the preoperative abdomen MRI, a surgical treatment is performed. Histological material is directed to the pathologist, who carried out the histological staging by the malignancy degree (low, intermediate, high). The data is entered into the database and the relationship between ADC values and histological degrees of malignancy of nephroblastoma is investigated

Initially, or after preoperative chemotherapy, patients with a kidney tumor are examined on 3T MR scanner or 1.5T MR scanner, using 8-channel body coil. A standard MRI study of the abdomen with contrast enhancement is performed. DWI (diffusion weighted) images are included in the standard investigation package and consist of diffusion maps (DWI 3b) with 3 b-factors (50; 600; 800 or others, optional). Then, using Philips workstation (ISP 9.0, Philips, Netherlands), DWI mapping and ADC values collection (mm2/s) are performed. The placement of region of interest (ROI) is selected in the kidney mass in a solid and cystic area with a size up to 100 mm2. The values are entered in the table due to the stage of the chemotherapy.

After the preoperative abdomen MRI, a surgical treatment is performed. Histological material is directed to the pathologist, who carried out the histological staging by the malignancy degree (low, intermediate, high). The data is entered into the database and the relationship between ADC values and histological degrees of malignancy of nephroblastoma is investigated.

DWI in the Diagnosis of Histological Types of Nephroblastoma in Children

Diffusion-weighted Images as an Additional Method for Diagnosing Histological Types of Nephroblastoma in Children

Federal Research Institute of Pediatric Hematology, Oncology and Immunology

Neuroblastoma

Neuroectodermal Tumors, Primitive, Peripheral

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Neuroepithelial

Neoplasms, Germ Cell and Embryonal

Neoplasms, Glandular and Epithelial

Neuroepithelioma

Dermatologic Agents

Anti-Infective Agents

Tretinoin

Interferons

Interferon-alpha

Interferon alpha-2

Keratolytic Agents

IFN-alpha with retinoic acid

A body of preclinical data has provided a strong rationale for evaluating the combination of IFN-alpha with retinoic acid. The two drugs have different mechanisms of action and, when used in combination, show enhanced activity in both adult and pediatric tumor cell lines.

The combination of the antiproliferative and differentiation inducing effect of retinoids together with the antiproliferative, immunostimulatory and differentiation-potentiating effects of IFN-alpha warrant clinical investigation of this combination for the treatment of refractory pediatric malignancies.

A body of preclinical data has provided a strong rationale for evaluating the combination of IFN-alpha with retinoic acid. The two drugs have different mechanisms of action and, when used in combination, show enhanced activity in both adult and pediatric tumor cell lines. In the pediatric phase I trial which administered ATRA for 3 consecutive days/week repeated weekly, the AUC of ATRA decreased on day 1 to day 3 of drug administration but returned to day 1 levels at the beginning of subsequent weeks. This intermittent schedule of ATRA administration allowed for exposure to relatively high plasma concentrations of ATRA on a repetitive basis. The combination of ATRA/IFN-alpha 2a has demonstrated clinical activity in the pediatric phase I trial in neuroblastoma and Wilms' tumor. The combination of the antiproliferative and differentiation inducing effect of retinoids together with the antiproliferative, immunostimulatory and differentiation-potentiating effects of IFN-alpha warrant clinical investigation of this combination for the treatment of refractory pediatric malignancies.

A Phase II Trial of All-Trans-Retinoic Acid in Combination With Interferon-Alpha 2a in Children With Recurrent Neuroblastoma or Wilms' Tumor

National Cancer Institute (NCI)

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
A Study of Selinexor in People With Wilms Tumors and Other Solid Tumors	NCT05985161	Wilms Tumor Rhabdoid Tumor Malignant Perip... MPNST Nephroblastoma XPO1 Gene Mutat... Solid Tumor	Selinexor	12 Months -	Memorial Sloan Kettering Cancer Center
A Study of Selinexor in People With Wilms Tumors and Other Solid Tumors	NCT05985161	Wilms Tumor Rhabdoid Tumor Malignant Perip... MPNST Nephroblastoma XPO1 Gene Mutat... Solid Tumor	Selinexor	12 Months -	Memorial Sloan Kettering Cancer Center
Pharmacogenetic Study of Antimitotic Therapies Involved in Hepatic VOD in Children With Nephroblastoma or ALL	NCT04168788	Hepatic Veno-Oc... Nephroblastoma Acute Lymphobla...	Blood test for ...	6 Months - 18 Years	University Hospital, Angers
Vascular Thrombus Involvement in Nephroblastoma	NCT05195411	Nephroblastoma ...		- 17 Years	Assistance Publique - Hôpitaux de Paris
DWI in the Diagnosis of Histological Types of Nephroblastoma in Children	NCT04814758	Nephroblastoma ...	MRI DWI sequenc...	6 Days - 18 Years	Federal Research Institute of Pediatric Hematology, Oncology and Immunology
DWI in the Diagnosis of Histological Types of Nephroblastoma in Children	NCT04814758	Nephroblastoma ...	MRI DWI sequenc...	6 Days - 18 Years	Federal Research Institute of Pediatric Hematology, Oncology and Immunology
A Phase II Trial of All-Trans-Retinoic Acid in Combination With Interferon-Alpha 2a in Children With Recurrent Neuroblastoma or Wilms' Tumor	NCT00001509	Nephroblastoma Neuroblastoma	IFN-alpha with ...	-	National Institutes of Health Clinical Center (CC)

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