Neoplasms

All Conditions

Digestive System Diseases

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Diseases and Abnormalities at or Before Birth

Skin and Connective Tissue Diseases

Symptoms and General Pathology

Rare Diseases

Osteosarcoma

Neuroblastoma

Sarcoma

Liver Neoplasms

Wilms Tumor

Sarcoma, Ewing

Rhabdomyosarcoma

Neoplasms, Germ Cell and Embryonal

Neoplasms, Connective and Soft Tissue

Neoplasms by Histologic Type

Neuroectodermal Tumors, Primitive, Peripheral

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Neuroepithelial

Neoplasms, Glandular and Epithelial

Neoplasms, Nerve Tissue

Neoplasms, Bone Tissue

Neoplasms, Connective Tissue

Myosarcoma

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

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Liver Diseases

Soft Tissue Sarcoma

Germ Cells Tumors

Wilms' Tumor

Ewing Sarcoma

Neuroepithelioma

Antineoplastic Agents

All Drugs and Chemicals

Anti-Infective Agents

Doxorubicin

Liposomal doxorubicin

Anti-Bacterial Agents

Antibiotics, Antitubercular

Enzyme Inhibitors

LTLD will be administered intravenously in combination with MR-HIFU ablation on day 1 of every 21 day cycle. There will be two potential dose escalation of LTLD with highest dose not to exceed the adult recommended MTD. Patients may receive up to a total of 6 cycles.

LTLD at dose determined from Part A will be administered intravenously on day 1 of every 21 day cycle. MR-HIFU induced MHT will follow immediately post LTLD infusion for one hour to target area with target temperatures of 40-45°C. Patients may receive up to a total of 6 cycles

Magnetic resonance (MR)-high intensity focused ultrasound (HIFU) provides precise controlled delivery of heat by focusing ultrasound energy inside a lesion using an external applicator that is completely non-invasive and non-ionizing.

Magnetic resonance high intensity focused ultrasound

A heat-activated formulation of liposomal doxorubicin with unique property of heat-activated release of doxorubicin, an active agent in most pediatric solid tumors.

Lyso-thermosensitive liposomal doxorubicin

AeRang Kim, MD, PhD

This study is looking to determine the maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D) of lyso-thermosensitive liposomal doxorubicin (LTLD) administered in combination with MR-HIFU in children with relapsed/refractory solid tumors, which may include but are not limited to rhabdomyosarcoma and other soft tissue sarcomas, Ewing's sarcoma family of tumors, osteosarcoma, neuroblastoma, Wilms' tumor, hepatic tumors, and germ cell tumors.

This is phase 1 trial of LTLD with MR-HIFU induced heating in children and young adults with relapsed/refractory solid tumors.

Part A of the trial will be a traditional dose escalation study to determine the pediatric MTD/RP2D of LTLD combined with MR-HIFU ablation which allows for release of doxorubicin in the ablation zone and peri-ablation margins.

Part B of the trial will combine LTLD at the MTD/RP2D with MR-HIFU induced mild hyperthermia (MHT) in an expanded cohort.

A Phase I Study of Lyso-thermosensitive Liposomal Doxorubicin and MR-HIFU for Pediatric Refractory Solid Tumors

A Phase I Study of Lyso-thermosensitive Liposomal Doxorubicin (LTLD, ThermoDox®) and Magnetic Resonance-Guided High Intensity Focused Ultrasound (MR-HIFU) for Relapsed or Refractory Solid Tumors in Children, Adolescents, and Young Adults

To determine the maximum tolerated dose (MTD) or recommended phase 2 dose (RP2D) of LTLD administered in combination with MR-HIFU ablation in children with relapsed/refractory solid tumors by examining blood samples collected from participants

To define and describe the toxicities of LTLD administered in combination with MR-HIFU as measured by reportable adverse events of participants as per the CTCAE v 4.0

Analyze blood samples of participants to characterize the pharmacokinetic properties of LTLD administered in combination with MR-HIFU

To determine the feasibility of LTLD administered at the recommended dose in combination with MR-HIFU induced mild hyperthermia (MHT) as determined by patient outcomes and adverse events

To preliminarily determine the antitumor activity of LTLD with MR-HIFU within the confines of a phase 1 study by examining the response of target lesions using RECIST criteria v1.1

To determine changes in symptoms and quality of life in children treated with LTLD and MR-HIFU by administering the Symptom Distress Scale and Peds QL v4.0 to participants

To determine the changes in immune markers in children treated with LTLD and MR-HIFU by examining blood samples from participants

AeRang Kim

MD, PhD

Behaviors and Mental Disorders

Fibromatosis, Aggressive

Aggression

Fibroma

Neoplasms, Fibrous Tissue

Desmoid Tumor

Magnetic Resonance High Intensity Focused Ultrasound (MR-HIFU) ablative therapy for children with recurrent or relapsed solid tumors.

MR-High intensity focused ultrasound (HIFU) is an ultrasound based technology which allows for non-invasive thermal ablation of tumors under the guidance of MR thermography.

Magnetic Resonance High Intensity Focused Ultrasound

The purpose of this study is to determine if Magnetic Resonance guided High Intensity Focused Ultrasound ablative therapy is safe and feasible for children, adolescents, and young adults with refractory or relapsed solid tumors.

Magnetic Resonance (MR)-guided high intensity focused ultrasound (HIFU) is an innovative technique that allows for non-invasive thermal ablation of tissue. Advantages over conventional local tumor control such as surgery, radiation, or radiofrequency are that MR-HIFU is completely non-invasive, non-ionizing, and enables ablation of large tumor volumes with avoidance of adjacent tissue injury. This study will evaluate the safety and feasibility of MR-HIFU ablative therapy in children, adolescents, and young adults with refractory or relapsed solid tumors that are located in bone or soft tissue in close proximity to bone. Patients ≤ 30 years of age with refractory or relapsed solid tumors with measurable target lesions that are located in bone or soft tissue in close proximity to bone are eligible. Tolerability will be defined during the 14 days following MR-HIFU ablation. Patients will continue to be followed for tumor response and secondary outcomes for up to one year post ablation treatment.

MR-guided High Intensity Focused Ultrasound (HIFU) on Pediatric Solid Tumors

Safety and Feasibility Study of Using MR-guided High Intensity Focused Ultrasound (HIFU) for the Ablation of Relapsed or Refractory Pediatric Solid Tumors

Toxicity will be evaluated using CTCAEv4. Adverse events will be summarized descriptively with tabulations of adverse event type, severity, and relationship to study treatment.

We will preliminarily define tumor response from MR-HIFU ablative therapy assessed according to a modified Response Evaluation Criteria in Solid Tumors (RECIST). We will also evaluate functional tumor response using FDG-PET post MR-HIFU ablative treatment for patients with PET avid target lesions.

We will use a validated symptom distress scale and quality of life metrics pre- and post-therapy at scheduled intervals.

Changes in immune markers from baseline and post therapy will be evaluated.

Infections

Eye Diseases

Nervous System Diseases

Mycoses

Retinoblastoma

Brain Neoplasms

Central Nervous System Neoplasms

Nervous System Neoplasms

Brain Diseases

Central Nervous System Diseases

Communicable Diseases

Bacterial Infections

Bacterial Infections and Mycoses

Retinal Neoplasms

Eye Neoplasms

Eye Diseases, Hereditary

Retinal Diseases

Itraconazole

Hydroxyitraconazole

Clotrimazole

Miconazole

Antifungal Agents

Cytochrome P-450 Enzyme Inhibitors

Hormones

Hormone Antagonists

Cytochrome P-450 CYP3A Inhibitors

2.5 mg/kg twice daily for the first two days --\> once daily

itraconazole

KiWoong Sung, MD, PhD

The purpose of this study is to investigate whether the prophylactic use of itraconazole is a better option than empirical use of itraconazole in the management (prevention and treatment) of fungal infection associated with high-dose chemotherapy and autologous hematopoietic stem cell transplantation in children with high-risk solid tumor.

With the advance of chemoradiotherapy, survival of patients, especially children, with malignant disease has improved. However, prognosis is still poor with conventional chemotherapy if patients have an advanced or high-risk tumor at diagnosis. Outcome in advanced or high-risk pediatric solid tumor such as advanced neuroblastoma, high-risk brain tumor, or recurrent pediatric solid tumor is still not satisfactory with conventional chemotherapy. In this context, investigators have explored the possible efficacy of high-dose chemotherapy (HDCT) and autologous stem cell transplantation (ASCT) in patients with high-risk or relapsed pediatric solid tumor. Efficacy of HDCT and ASCT has been well demonstrated in high-risk neuroblastoma, high-risk brain tumor, and recurrent pediatric solid tumors. Therefore, now, HSCT and ASCT is the most important treatment modality in the treatment of a variety of pediatric solid tumors poorly responding to conventional chemotherapy.

However, although HDCT and ASCT has improved the survival of patients with high-risk tumor, a variety of clinical issues associated with HDCT and ASCT are present causing significant morbidity and even mortality. The most frequent cause of morbidity associated with HDCT and ASCT is infection. Once high-dose myeloablative chemotherapeutic agents are administered, most hematopoietic cells in bone marrow die and prolonged marrow aplasia is unavoidable even after autologous hematopoietic stem cells infusion because it takes time for infused stem cells to reconstitute sufficient hematopoietic function. In addition, high-dose chemotherapy results in severe gastrointestinal mucosal damage which facilitates bacterial and/or fungal infection via damaged mucosal barrier. Therefore, infection is a major cause of morbidity and mortality associated with HDCT and ASCT. Common pathogens associated with infection during HDCT and ASCT are bacteria and fungi.

To reduce the chance of infection and therefore, to reduce the morbidity and mortality from severe infection, various prophylactic antibiotics including antibacterial, antifungal, and antiviral agents have been used according to standard guideline in allogeneic stem cell transplantation. However, in autologous transplantation for solid tumor in which hematologic recovery is rapid and immune suppression is less severe than allogeneic transplantation, there is no standard guideline for the use of prophylactic antibiotics whereas infection is the most important cause of morbidity. Standard guideline for the use of prophylactic antifungal agent is also not available. While some institutes use anti-fungal agent prophylactically, others use antifungal agent empirically only when neutropenic fever persist despite of empirical use of antibacterial agents.

HDCT in pediatric solid tumor is generally more intensive, and therefore, usually cause more severe mucositis than that in adult tumor. Severe mucositis facilitates fungal infection via damaged mucosal barrier (mainly by Candida species). Therefore, use of prophylactic anti-fungal agent may reduce the morbidity and mortality associated with HDCT and ASCT in pediatric solid tumor. However, there is no randomized clinical study to evaluate the efficacy of prophylactic use of anti-fungal agent to date.

Itraconazole is one of newly developed antifungal agents and many physicians started to use itraconazole as first-line antifungal agent in the management of neutropenic fever in immunocompromised patients. However, the efficacy of prophylactic itraconazole has not been established in children with solid tumor, especially who receive HDCT and ASCT.

In this context, we are going to evaluate the efficacy of prophylactic use of itraconazole in children with high-risk solid tumors during HDCT and ASCT. "Prophylactic" group will be treated with itraconazole once ANC fall below 500/uL regardless of infection and "Empirical" group will be treated with itraconazole only when high fever persists despite of treatment with first-line anti-bacterial agents.

Efficacy of Prophylactic Itraconazole in High-Dose Chemotherapy and Autologous Hematopoietic Stem Cell Transplantation

Clinical Study to Evaluate the Efficacy of Prophylactic Itraconazole in High-Dose Chemotherapy and Autologous Hematopoietic Stem Cell Transplantation for Pediatric Solid Tumors

Samsung Medical Center

Ki Woong Sung

Recurrence

Disease Attributes

Antibodies

Antibodies, Monoclonal

Immunoglobulins

Endothelial Growth Factors

Mitogens

Ramucirumab

Angiogenesis Inhibitors

Growth Inhibitors

(Part A-Non-CNS Solid Tumors) Escalating doses of 8 milligrams per kilogram (mg/kg) or 12 mg/kg Ramucirumab administered as an intravenous infusion every 2 weeks (Q2W) with 3 doses per 42 day cycle.

(Part B-CNS Tumors) Participants received 12 mg/kg Ramucirumab as an intravenous injection Q2W with 3 doses per cycle.

Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST)

The main purpose of this study is to evaluate the safety of the study drug known as ramucirumab in children with recurrent or refractory solid tumors including central nervous system (CNS) tumors.

A Study of Ramucirumab (LY3009806) in Children With Refractory Solid Tumors

A Phase 1 Study Of Ramucirumab, a Human Monoclonal Antibody Against the Vascular Endothelial Growth Factor-2 (VEGFR-2) Receptor in Children With Refractory Solid Tumors, Including CNS Tumors

A DLT is defined as an Adverse Event (AE) that is likely related to the study medication or combination, and fulfills any one of the following criteria, graded according to the National Cancer Institute's (NCI) Common Terminology Criteria for Adverse Events (NCI-CTCAE) Version 5.0:

1. Any death not clearly due to the underlying disease or extraneous causes 2. Neutropenic fever 2. Any Grade ≥3 non-hematologic toxicity 3. Grade ≥4 neutropenia or thrombocytopenia \>7 days 4. Grade ≥3 thrombocytopenia with bleeding 5. Grade ≥3 nausea/vomiting or diarrhea\>72 hours with adequate antiemetic and other supportive care 6. Grade ≥3 fatigue ≥1 week 7. Grade ≥3 electrolyte abnormality that lasts\>72 hours, unless the Participant has clinical symptoms, in which case all Grade 3+electrolyte abnormality regardless of duration should count as a DLT.

8. Grade ≥3 prolongation of QT interval corrected using the Fridericia formula on 2 separate electrocardiogram readings approximately 5 min apart.

Population Pharmacokinetics (PK): Minimum observed plasma concentration of Ramucirumab.

Number of participants with positive treatment emergent anti-ramucirumab antibodies was summarized by treatment group. A treatment-emergent anti-drug antibodies (TEADA) sample was defined as: a post treatment sample with at least a 4-fold increase in titer from pre treatment sample; or 1:20 post treatment titer for participants that had no detectable ADA titer at baseline.

Overall response rate is the best response of complete response (CR) or partial response (PR) as classified by the independent central review according to the Response Evaluation Criteria In Solid Tumors (RECIST v1.1). CR is a disappearance of all target and non-target lesions and normalization of tumor marker level. PR is an at least 30% decrease in the sum of the diameters of target lesions (taking as reference the baseline sum diameter) without progression of non-target lesions or appearance of new lesions. Overall response rate is calculated as a total number of participants with CR or PR divided by the total number of participants per cohort with at least 1 measurable lesion, multiplied by 100. Progressive Disease (PD) was at least a 20% increase in the sum of the diameters of target lesions, with reference being the smallest sum on study and an absolute increase of at least 5 mm, or unequivocal progression of non-target lesions, or 1 or more new lesions.

Disease Control Rate (DCR) was the percentage of participants with a best overall response of CR, PR, or Stable Disease (SD) as per Response using RECIST v1.1 criteria. CR defined as the disappearance of all target and non-target lesions and no appearance of new lesions. PR defined as at least a 30% decrease in the sum of the LD of target lesions (taking as reference the baseline sum LD), no progression of non-target lesions, and no appearance of new lesions. SD was neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD for target lesions, no progression of non-target lesions, and no appearance of new lesions. PD was at least a 20% increase in the sum of the diameters of target lesions, with reference being the smallest sum on study and an absolute increase of at least 5 mm, or unequivocal progression of non-target lesions, or 1 or more new lesions.

DOR was the time from the date of first evidence of complete response or partial response to the date of objective progression or the date of death due to any cause, whichever is earlier. CR and PR were defined using the RECIST v1.1. CR defined as the disappearance of all target and non-target lesions and no appearance of new lesions. PR defined as at least a 30% decrease in the sum of the LD of target lesions (taking as reference the baseline sum LD), no progression of non-target lesions, and no appearance of new lesions. If a responder was not known to have died or have objective progression as of the data inclusion cutoff date, duration of response was censored at the last adequate tumor assessment date. PD was at least a 20% increase in the sum of the diameters of target lesions, with reference being the smallest sum on study and an absolute increase of at least 5 mm, or unequivocal progression of non-target lesions, or 1 or more new lesions.

Overall survival is defined as the time from date of randomization to the date of death (due to any cause). For participants whose last known status is alive at the data cutoff date for the analysis, time will be censored as the last contact date prior to the data cutoff date.

Children's Oncology Group

Eli Lilly and Company

All randomized participants who received at least one dose of study drug.

Participants received 8 mg/kg Ramucirumab administered as an intravenous infusion Q2W with 3 doses per 42 day cycle.

8 mg/kg Ramucirumab (Part A)

Participants received 12 mg/kg Ramucirumab as an intravenous injection Q2W with 3 doses per cycle.

12 mg/kg Ramucirumab (Part A)

12 mg/kg Ramucirumab (Part B)

Total

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

United States

Region of Enrollment

Chief Medical Officer

All randomized participants from Part A, who received at least one dose of study drug.

Part A: Number of Participants With Dose Limiting Toxicities (DLTs): Maximum Tolerated Dose of Ramucirumab

Cycle 1 Day 1

Cycle 1 Day 43

Participants received 8 mg/kg Ramucirumab administered as an intravenous infusion every 2 weeks (Q2W) with 3 doses per 42 day cycle.

8 mg/kg Ramucirumab

12 mg/kg Ramucirumab

All randomized participants who received at least one dose of study drug and had evaluable PK data. Per protocol, 12 mg/kg Ramucirumab PK data were reported per dose level combining Part A and B participants.

Population Pharmacokinetics (PK): Minimum Concentration (Cmin) of Ramucirumab

Number of Participants With Anti-Ramucirumab Antibodies

Overall Response Rate (ORR): Percentage of Participants Who Achieve Complete Response (CR) or Partial Response (PR)

Percentage of Participants With a Best Overall Response of Complete Response (CR), Partial Response (PR) or Stable Disease (SD): Disease Control Rate (DCR)

Zero participants analyzed. Duration of response was not evaluable, as there were no participants with CR or PR.

Duration of Response (DOR)

Overall Survival

Participants received 8 milligram per kilogram \[mg/kg\] Ramucirumab administered as an intravenous infusion every 2 weeks (Q2W) with 3 doses per 42 day cycle.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
A Phase I Study of Lyso-thermosensitive Liposomal Doxorubicin and MR-HIFU for Pediatric Refractory Solid Tumors	NCT02536183	Pediatric Cance... Solid Tumors Rhabdomyosarcom... Ewing Sarcoma Soft Tissue Sar... Osteosarcoma Neuroblastoma Wilms Tumor Hepatic Tumor Germ Cell Tumor...	Magnetic resona... Lyso-thermosens...	- 30 Years	Children's National Research Institute
MR-guided High Intensity Focused Ultrasound (HIFU) on Pediatric Solid Tumors	NCT02076906	Relapsed Pediat... Refractory Pedi... Rhabdomyosarcom... Ewing Sarcoma Osteosarcoma Neuroblastoma Wilms Tumor Hepatic Tumor Germ Cell Tumor Desmoid Tumor	Magnetic Resona...	- 30 Years	Children's National Research Institute
A Phase I Study of Lyso-thermosensitive Liposomal Doxorubicin and MR-HIFU for Pediatric Refractory Solid Tumors	NCT02536183	Pediatric Cance... Solid Tumors Rhabdomyosarcom... Ewing Sarcoma Soft Tissue Sar... Osteosarcoma Neuroblastoma Wilms Tumor Hepatic Tumor Germ Cell Tumor...	Magnetic resona... Lyso-thermosens...	- 30 Years	Children's National Research Institute
Efficacy of Prophylactic Itraconazole in High-Dose Chemotherapy and Autologous Hematopoietic Stem Cell Transplantation	NCT00336531	Neuroblastoma Brain Tumor Retinoblastoma Wilms Tumor Mycoses	itraconazole	- 15 Years	Samsung Medical Center
A Study of Ramucirumab (LY3009806) in Children With Refractory Solid Tumors	NCT02564198	Pediatric Solid... Refractory Tumo... Recurrent Tumor CNS Malignancie...	Ramucirumab	12 Months - 21 Years	Eli Lilly and Company
MR-guided High Intensity Focused Ultrasound (HIFU) on Pediatric Solid Tumors	NCT02076906	Relapsed Pediat... Refractory Pedi... Rhabdomyosarcom... Ewing Sarcoma Osteosarcoma Neuroblastoma Wilms Tumor Hepatic Tumor Germ Cell Tumor Desmoid Tumor	Magnetic Resona...	- 30 Years	Children's National Research Institute

Spots Global Cancer Trial Database for relapsed pediatric solid tumors