Neoplasms

Blood and Lymph Conditions

Immune System Diseases

All Conditions

Nervous System Diseases

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Diseases and Abnormalities at or Before Birth

Skin and Connective Tissue Diseases

Rare Diseases

Lymphoma

Glioblastoma

Glioma

Sarcoma

Hodgkin Disease

Brain Neoplasms

Osteosarcoma

Wilms Tumor

Medulloblastoma

Diffuse Intrinsic Pontine Glioma

Neuroblastoma

Sarcoma, Ewing

Neuroectodermal Tumors, Primitive, Peripheral

Ependymoma

Rhabdomyosarcoma

Sarcoma, Synovial

Desmoplastic Small Round Cell Tumor

Rhabdoid Tumor

Gliosarcoma

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms by Histologic Type

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

Neoplasms, Connective and Soft Tissue

Central Nervous System Neoplasms

Nervous System Neoplasms

Brain Diseases

Central Nervous System Diseases

Neoplasms, Neuroepithelial

Neoplasms, Germ Cell and Embryonal

Neoplasms, Glandular and Epithelial

Neoplasms, Nerve Tissue

Neoplasms, Bone Tissue

Neoplasms, Connective Tissue

Myosarcoma

Lymphosarcoma

Soft Tissue Sarcoma

Hodgkin Lymphoma

Germ Cells Tumors

Wilms' Tumor

Ewing Sarcoma

Brain Tumor, Childhood

Synovial Sarcoma

Neuroepithelioma

Malignant Germ Cell Tumor

Gliomatosis Cerebri

IV dose of CLR 131, increased/decreased by dose level; single or fractionated dose

CLR 131

Jarrod Longcor

The study evaluates CLR 131 in children, adolescents, and young adults with relapsed or refractory malignant solid tumors and lymphoma and recurrent or refractory malignant brain tumors for which there are no standard treatment options with curative potential.

Even with standard, highly toxic multimodality therapies and salvage regimen, most pediatric patients with primary metastatic or relapsed solid tumors are confronted with a poor prognosis. For these patients there is currently no accepted successful treatment regimen. There is a need for new drugs, including targeted radiopharmaceuticals, preferably with cancer-specific uptake and broad applicability for these rare pediatric malignancies.

CLR 131 is a radioiodinated therapeutic that exploits the selective uptake and retention of phospholipid ethers (PLEs) by malignant cells. Cellectar Biosciences' novel cancer-targeted small-molecule compound (CLR1404) is radiolabeled with the isotope iodine-131 (I-131). CLR 131 has demonstrated tumor selective uptake across numerous adult and pediatric cancer cell types. Therapeutic efficacy has been demonstrated in various pediatric and adult-type cancer xenograft models, confirming the ability of CLR 131 to target tumors.

Based on the critical unmet medical need for effective agents with novel mechanisms of action in relapsed pediatric cancers and initial preclinical and clinical experience with radioiodinated CLR1404, Cellectar Biosciences has chosen to assess CLR 131 in a phase 1 pediatric trial.

Dose Escalation Study of CLR 131 in Children, Adolescents, and Young Adults With Relapsed or Refractory Malignant Tumors Including But Not Limited to Neuroblastoma, Rhabdomyosarcoma, Ewings Sarcoma, and Osteosarcoma

An Open-Label, Dose Escalation, Efficacy, and Safety Study of CLR 131 in Children, Adolescents, and Young Adults With Select Solid Tumors, Lymphoma, and Malignant Brain Tumors

DLT will be assessed by physical examination, vital signs, and laboratory values

Dose and regimen to be used in Phase 2 trials of CLR 131 in children, adolescents, and young adults

Response assessment per applicable criteria (e.g., Neuroblastoma Response Criteria (modified); RECIST 1.1; positron emission tomography response criteria in solid tumors (PERCIST); RANO)

Assessment via 131-I/CLR 131 SPECT/CT scans

Time from first infusion of CLR 131 until progression or recurrence of disease

Time from first infusion of CLR 131 until death due to any reason

Assessment of dosimetry via whole body planar imaging

Cellectar Biosciences, Inc.

Symptoms and General Pathology

Respiratory Tract (Lung and Bronchial) Diseases

Recurrence

Hepatoblastoma

Histiocytosis, Langerhans-Cell

Histiocytosis

Lymphoma, Non-Hodgkin

Disease Attributes

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

Lung Diseases

Lung Diseases, Interstitial

Respiratory Tract Diseases

Langerhans Cell Histiocytosis

Antineoplastic Agents

All Drugs and Chemicals

Vemurafenib

Protein Kinase Inhibitors

Enzyme Inhibitors

Patients receive vemurafenib PO BID on day 1-28. Cycles repeat every 28 days for up to 2 years in the absence of disease progression or unacceptable toxicity.

Laboratory Biomarker Analysis

AeRang Kim

This phase II Pediatric MATCH trial studies how well vemurafenib works in treating patients with solid tumors, non-Hodgkin lymphoma, or histiocytic disorders with BRAF V600 mutations that have spread to other places in the body (advanced) and have come back (recurrent) or do not respond to treatment (refractory). Vemurafenib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

PRIMARY OBJECTIVE:

I. To determine the objective response rate (ORR; complete response + partial response) in pediatric patients treated with vemurafenib with advanced solid tumors (including central nervous system \[CNS\] tumors), lymphomas or histiocytic disorders that harbor activating BRAF V600 mutations.

SECONDARY OBJECTIVES:

I. To estimate the progression free survival in pediatric patients treated with vemurafenib with advanced solid tumors (including CNS tumors), lymphomas or histiocytic disorders that harbor activating BRAF V600 mutations.

II. To obtain information about the tolerability of vemurafenib in children with relapsed or refractory cancer.

EXPLORATORY OBJECTIVE:

I. To explore approaches to profiling changes in tumor genomics over time through evaluation of circulating tumor deoxyribonucleic acid (DNA).

OUTLINE:

Patients receive vemurafenib orally (PO) twice daily (BID) on day 1-28. Cycles repeat every 28 days for up to 2 years in the absence of disease progression or unacceptable toxicity.

Vemurafenib in Treating Patients With Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphoma, or Histiocytic Disorders With BRAF V600 Mutations (A Pediatric MATCH Treatment Trial)

NCI-COG Pediatric MATCH (Molecular Analysis for Therapy Choice)- Phase 2 Subprotocol of Vemurafenib in Patients With Tumors Harboring BRAF V600 Mutations

Will explore approaches to profiling changes in tumor genomics over time through evaluation of circulating tumor deoxyribonucleic acid. Will be summarized with simple summary statistics and will be descriptive in nature.

ORR will be defined as complete response + partial response and assessed by Response Evaluation Criteria in Solid Tumors (RECIST) guideline (version 1.1). Will be calculated as the percent of evaluable patients who are responders, and confidence intervals will be constructed using the Wilson score interval method.

PFS will be defined as time from the initiation of protocol treatment to the I of any of the following events: disease progression or disease recurrence or death from any cause. Patients with local calls of disease progression (i.e. calls made by the treating institution), will be counted as having had an event, even if the central review does not declare progression. PFS along with the confidence intervals will be estimated using the Kaplan-Meier method.

Percentage of patients experiencing grade 3 or higher adverse events will be evaluated according to National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0. All patients who receive at least one dose of protocol therapy will be considered in the evaluation of toxicity.

National Cancer Institute (NCI)

Adverse event reporting is collected routinely using case report forms. The SAE table reflects NCI Common Terminology Criteria for Adverse Events (CTCAEs) submitted by the institution via expedited reporting (NCI AdEERs / CAeRs). All remaining CTCAEs collected by means other than expedited reporting are non-serious and are reported in the "AE Other" table. Ineligible patients are excluded from reporting of adverse events. All-Cause Mortality includes all deaths collected on the study.

Treatment (Vemurafenib)

Age, Categorical

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

United States

Region of Enrollment

Results Reporting Coordinator

Objective Response Rate (ORR)

Progress Free Survival (PFS)

Percentage of Patients Experiencing Grade 3 or Higher Adverse Events

Changes in Tumor Genomics

Overall Study

Gland and Hormone Related Diseases

Digestive System Diseases

Eye Diseases

Ovarian Neoplasms

Carcinoma, Ovarian Epithelial

Carcinoma, Renal Cell

Liver Neoplasms

Retinoblastoma

Teratoma

Testicular Neoplasms

Astrocytoma

Chordoma

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Liver Diseases

Retinal Neoplasms

Eye Neoplasms

Eye Diseases, Hereditary

Retinal Diseases

Ovarian Cancer

Ovarian Epithelial Cancer

Renal Cell Carcinoma

Brain Tumor, Adult

Ovarian Germ Cell Tumor

Testicular Germ Cell Tumor

Extragonadal Germ Cell Tumor

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

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Dose Escalation Study of CLR 131 in Children, Adolescents, and Young Adults With Relapsed or Refractory Malignant Tumors Including But Not Limited to Neuroblastoma, Rhabdomyosarcoma, Ewings Sarcoma, and Osteosarcoma	NCT03478462	Pediatric Solid... Pediatric Lymph... Pediatric Brain... DIPG Neuroblastoma Ewing Sarcoma Rhabdomyosarcom... Osteosarcoma	CLR 131	2 Years - 25 Years	Cellectar Biosciences, Inc.
Vemurafenib in Treating Patients With Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphoma, or Histiocytic Disorders With BRAF V600 Mutations (A Pediatric MATCH Treatment Trial)	NCT03220035	Advanced Malign... Ann Arbor Stage... Ann Arbor Stage... Ependymoma Ewing Sarcoma Hepatoblastoma Langerhans Cell... Malignant Germ ... Malignant Gliom... Osteosarcoma Peripheral Prim... Recurrent Child... Recurrent Child... Recurrent Malig... Recurrent Neuro... Refractory Mali... Refractory Neur... Refractory Non-... Refractory Prim... Rhabdoid Tumor Rhabdomyosarcom... Soft Tissue Sar... Wilms Tumor	Laboratory Biom... Vemurafenib	12 Months - 21 Years	National Cancer Institute (NCI)
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
Vemurafenib in Treating Patients With Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphoma, or Histiocytic Disorders With BRAF V600 Mutations (A Pediatric MATCH Treatment Trial)	NCT03220035	Advanced Malign... Ann Arbor Stage... Ann Arbor Stage... Ependymoma Ewing Sarcoma Hepatoblastoma Langerhans Cell... Malignant Germ ... Malignant Gliom... Osteosarcoma Peripheral Prim... Recurrent Child... Recurrent Child... Recurrent Malig... Recurrent Neuro... Refractory Mali... Refractory Neur... Refractory Non-... Refractory Prim... Rhabdoid Tumor Rhabdomyosarcom... Soft Tissue Sar... Wilms Tumor	Laboratory Biom... Vemurafenib	12 Months - 21 Years	National Cancer Institute (NCI)

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