Neoplasms

All Conditions

Symptoms and General Pathology

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Diseases and Abnormalities at or Before Birth

Skin and Connective Tissue Diseases

Rare Diseases

Carcinoma

Neoplasm Metastasis

Carcinoma, Renal Cell

Sarcoma

Osteosarcoma

Wilms Tumor

Sarcoma, Ewing

Neuroectodermal Tumors, Primitive, Peripheral

Kidney Neoplasms

Rhabdomyosarcoma

Rhabdoid Tumor

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplastic Processes

Neoplasms, Connective and Soft Tissue

Neoplasms by Histologic Type

Adenocarcinoma

Neoplasms, Glandular and Epithelial

Urologic Neoplasms

Urogenital Neoplasms

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Kidney Diseases

Urologic Diseases

Male Urogenital Diseases

Neoplasms, Bone Tissue

Neoplasms, Connective Tissue

Myosarcoma

Syndrome

Neoplastic Syndromes, Hereditary

Genetic Diseases, Inborn

Neoplasms, Neuroepithelial

Neoplasms, Germ Cell and Embryonal

Neoplasms, Nerve Tissue

Renal Cell Carcinoma

Clear Cell Renal Cell Carcinoma

Soft Tissue Sarcoma

Wilms' Tumor

Ewing Sarcoma

Neuroepithelioma

Participants with Wilms tumors or other primary renal tumors. Stereotactic Body Radiotherapy (SBRT) Dose Levels for each target lesion are three 8 Gy fractions for 24 Gy total.

Participants with Wilms tumors or other primary renal tumors. SBRT Dose Levels for each target lesion are three 10 Gy fractions for 30 Gy total.

Participants with Wilms tumors or other primary renal tumors. SBRT Dose Levels for each target lesion are three 12 Gy fractions for 36 Gy total.

Participants with Ewing sarcoma or rhabdomyosarcoma. SBRT Dose Levels for each target lesion are three 10 Gy fractions for 30 Gy total.

Participants with Ewing sarcoma or rhabdomyosarcoma.SBRT Dose Levels for each target lesion are three 12 Gy fractions for 36 Gy total.

Stereotactic Body Radiotherapy (SBRT)

Karen Marcus, MD

This research study is studying stereotactic body radiotherapy (SBRT) as a possible treatment for lung relapse of Ewing sarcoma, rhabdomyosarcoma, osteosarcoma, non-rhabdomyosarcoma soft tissue sarcoma, Wilms tumor or other primary renal tumor (including clear cell and rhabdoid). SBRT is a form of targeted radiotherapy that can treat very small tumors using a few large doses.

This research study is a Pilot Study, also known as a Phase I-II study, which means it is the first time investigators are examining this study intervention for patients with lung recurrence of Ewing sarcoma, rhabdomyosarcoma, osteosarcoma, nonrhabdomyosarcoma soft tissue sarcoma, Wilms tumor or other primary renal tumor (including clear cell and rhabdoid). This study tests the most appropriate dose, safety and efficacy of SBRT for the treatment of lung recurrence of these cancers in children. Standard radiotherapy is typically used to treat Ewing sarcoma and is used to treat lung recurrence. SBRT is being used to treat adults with small inoperable lung cancers; in such cases, SBRT has been shown to be effective and well-tolerated. SBRT is also used to treat bone metastases in adults and children.

Stereotactic Body Radiotherapy (SBRT) for Pulmonary Metastases in Ewing Sarcoma, Rhabdomyosarcoma, and Wilms Tumors

Dose Limiting Toxicities (DLT's) are toxicities experienced from start of therapy to 6 month. DLT's are assessed on the Common Terminology Criteria for Adverse Events (CTCAE) version 4.

DLTs are defined as follows:

Grade 2 or higher toxicities:

* Myelitis
* Esophageal fistula, perforation, hemorrhage

Grade 3 or higher toxicities considered to be a direct result of therapy:

* Pneumonitis
* Pericarditis, pericardial effusion
* Esophageal necrosis, stenosis, ulcer
* Dyspnea

Grade 4 toxicities:

* Esophagitis
* Pericardial tamponade
* Pulmonary toxicity excluding infectious pneumonia
* Skin toxicity
* Hemoptysis/pulmonary hemorrhage

Grade 5 toxicities, including:

* Pulmonary toxicity including pneumonitis
* Excluding infectious pneumonia

Three participants will enter the study in each cohort. If 0/3 patients experiences a DLT, this dose level will move forward to the Phase II and more participants will be enrolled.

Percentage of participants with response after 6 weeks. Response on treatment was considered to be Complete Response (CR) and Partial Response (PR) measured according Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria. For target lesions, CR is complete disappearance of all target lesions and PR is at least a 30% decrease in the sum of longest diameter.

Percentage of pulmonary lesions of participants with response after 6 weeks. Response on treatment was considered to be Complete Response (CR) measured according Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria. For target lesions, CR is complete disappearance of all target lesions.

Rate of local control (LC) of the index lesion after lung SBRT at 2 years. LC is defined as the absence of tumor progression within 1 cm of the primary tumor site. LC is measured by established methods.

Rate of distant lung failure-free survival defined lung failure or death from any cause at two years. Lung failure defined using established methods.

Grade 3 or higher adverse events as defined by controlled terminology criteria for adverse events (CTCAE) version 4.

Dana-Farber Cancer Institute

Karen J Marcus, M.D.

Serious Adverse Events (SAE's) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.

Participants with Ewing sarcoma or rhabdomyosarcoma. SBRT Dose Levels for each target lesion are three 10 Gy fractions for 30 Gy total.

Stereotactic Body Radiotherapy (SBRT)

Cohort 2 Dose Level 2 [Phase I]

Cohort 2 Dose Level 2 [Phase II]

Cohort 2 Dose Level 2 [Phase I and II]

Age, Continuous

Sex: Female, Male

Race/Ethnicity, Customized

Primary Tumor Histologies

Number of Lesions

The study had small sample size / weak accrual.

Karen Marcus MD

Number of Participants With Dose Limiting Toxicity [Phase I]

It is pre-specified in the protocol that Phase I and Phase II populations for each cohort are combined for this analysis

Overall Response Rate [Phase II]

Complete Response Rate [Phase II]

2 Year Local Control Rate [Phase II]

Percentage of Participants With 2-Year Failure-Free Survival [Phase II]

Number of Participants With Grade 3 or Higher Adverse Events [Phase I and II]

Overall Study

Musculoskeletal Diseases

Recurrence

Bone Neoplasms

Disease Attributes

Connective Tissue Diseases

Bone Diseases

Antineoplastic Agents

All Drugs and Chemicals

Irinotecan

Vaccines

Temozolomide

Immunomodulating Agents

Camptothecin

Topoisomerase I Inhibitors

Enzyme Inhibitors

Antineoplastic Agents, Alkylating

Alkylating Agents

Participants randomized to Group A received oral temozolomide 100 mg/m2 daily (Days 1-5), total dose 500 mg/m2/cycle) and oral irinotecan 50 mg/m2 daily (Days 1-5, total dose 250 mg/m2/cycle). Vigil immunotherapy was administered at a concentration of 1 X 10e6 cells/dose given via intradermal injection on Day 15 of each cycle. 1 cycle = 21 days

Participants continued treatment for a maximum of 12 cycles, or until disease progression, unacceptable toxicity, withdrawal of consent or other criterion is met for discontinuation from study.

Participants randomized to Group B received oral temozolomide 100 mg/m2 daily (Days 1-5), total dose 500 mg/m2/cycle) and oral irinotecan 50 mg/m2 daily (Days 1-5, total dose 250 mg/m2/cycle).

1 cycle = 21 days

Participants continued treatment for a maximum of 12 cycles, or until disease progression, unacceptable toxicity, withdrawal of consent or other criterion is met for discontinuation from study.

Participants randomized to Group B were able to receive Vigil immunotherapy at a concentration of 1 X 10e6 cells/dose given via intradermal injection on Day 15 of each cycle. Confirmation of progression by central radiologist and pre-approval from sponsor was required. 1 cycle = 21 days

Vigil is composed of autologous tumor cells harvested from the patient at the time of initial de-bulking surgery which are then transfected extracorporeally, with a plasmid encoding for the gene for GM-CSF, an immune-stimulatory cytokine, and a bifunctional, short hairpin RNA which specifically knocks down the expression of furin, the critical convertase responsible for production of the two TGβ isoforms.

Vigil

Injectable formulation of irinotecan was distributed from central supplier. 1 Cycle (5 doses of 50 mg/m2 per syringe) was drawn into provided oral syringes and dispenses to the subject with instructions to refrigerate until administration.

Dose: 100 mg/m2 daily, oral Schedule: Days 1-5, every 21 days Administered at least 1 hour before Irinotecan.

John Nemunaitis, MD

The goal of this clinical trial was to compare participants with first relapse or refractory Ewing's sarcoma when treated with investigational product (Vigil) in addition to the standard treatment of irinotecan and temozolomide compared to the standard treatment of irinotecan and temozolomide alone. The main question it aimed to answer is "Will participants who receive Vigil in addition to irinotecan and temozolomide have a prolonged time to progression and improved quality of life compared to the participants who receive irinotecan and temozolomide alone?".

This was a multicenter, Phase III study in participants with metastatic Ewing's sarcoma Family of Tumors (ESFT) refractory/intolerant or recurrent to 1 prior line of chemotherapy. Participants who agreed to participation had tumor tissue harvested from a scheduled standard surgical procedure (e.g., tumor biopsy or palliative resection). The tumor tissue removed was shipped to Gradalis, Inc. to attempt to manufacture the investigational product, Vigil.

Subjects who met eligibility criteria including manufacture of a minimum of 4 doses of Vigil were randomized 1:1 to either Group A (Vigil + Irinotecan + Temozolomide (Tem/Iri)) or Group B (Irinotecan + Temozolomide). Screening for the main portion of the study occurred as early as one week but no later than 8 weeks following tumor procurement.

Subjects received repeat cycles of treatment until disease progression, unacceptable toxicity, withdrawal of consent or other criterion was met for discontinuation from study. Subjects randomized to Group A (Vigil + Tem/Iri) received up to 12 doses depending upon the quantity of Vigil manufactured from the surgical specimen. 1 cycle = 21 days. If irinotecan + temozolomide was administered beyond 12 cycles, it was administered off study. Subjects randomized to Group B (Tem/Iri) may have crossed over to receive single agent Vigil every 21 days following End of Treatment assessment and documented disease progression confirmed by central radiology vendor, for up to 12 doses of Vigil depending upon the quantity of Vigil manufactured.

Participants were managed in an outpatient setting. Hematologic function, liver enzymes, renal function and electrolytes will be monitored. Blood for immune function analyses including IFNγ-ELISPOT analysis of cytotoxic T cell activation in response to autologous tumor antigens will be collected at tissue procurement, post-procurement screening and Day 1 (prior to chemotherapy administration) at Cycles 2, 4, and 6, end of treatment (EOT), 3 months after EOT, and every 6 months thereafter. Blood for ctDNA analysis was collected at tissue procurement, prior to chemotherapy administration at baseline and on Day 1 prior to chemotherapy administration at Cycles 2, 3, 4, and 6, and EOT. After progression, participants were contacted quarterly for documentation of post study therapies and survival status information.

Participants were randomized 1:1 to either Group A (Vigil + irinotecan and temozolomide) or Group B (irinotecan and temozolomide alone). Participants randomized to Group B were able to receive Vigil (Cross-Over) after confirmation of progression by central radiologist and sponsor approval.

A Trial For Participants With Ewing's Sarcoma Treated With Vigil in Combination With Irinotecan and Temozolomide

A Multi-Center Phase III, Randomized, Open-Label Trial of Vigil (Bi-shRNAfurin and GMCSF Augmented Autologous Tumor Cell Immunotherapy) in Combination With Irinotecan and Temozolomide as a Second-Line Regimen for Ewing's Sarcoma

Progression Free Survival (PFS) is defined as the time from randomization to the event of disease recurrence/progression according to Response Evaluation Criteria In Solid Tumors (RECIST) criteria (version 1.1) for target lesions and assessed CT/MRI by local investigator.

OS is defined as time from randomization to death or to the date of last follow-up. The date of last follow-up confirming survival will be used as the censoring date for subjects who are alive and/or do not have a known date of death.

ORR is defined as the proportion of participants who have prolonged stable disease or a partial or complete response or complete response to therapy according to RECIST 1.1.

Participants were considered eligible for treatment, if the tissue submitted to Gradalis met all criteria, including manufacturing product release criteria.

Gradalis, Inc.

Participants randomized to Group A received oral temozolomide 100 mg/m2 daily (Days 1-5), total dose 500 mg/m2/cycle) and oral irinotecan 50 mg/m2 daily (Days 1-5, total dose 250 mg/m2/cycle). Vigil immunotherapy was administered at a concentration of 1 X 10e6 cells/dose given via intradermal injection on Day 15 of each cycle. 1 cycle = 21 days

Participants continued treatment for a maximum of 12 cycles, or until disease progression, unacceptable toxicity, withdrawal of consent or other criterion was met for discontinuation from study.

Group A: Vigil in Combination With Irinotecan and Temozolomide

Participants randomized to Group B received oral temozolomide 100 mg/m2 daily (Days 1-5), total dose 500 mg/m2/cycle) and oral irinotecan 50 mg/m2 daily (Days 1-5, total dose 250 mg/m2/cycle).

1 cycle = 21 days

Participants continued treatment for a maximum of 12 cycles, or until disease progression, unacceptable toxicity, withdrawal of consent or other criterion was met for discontinuation from study.

Group B: Irinotecan and Temozolomide

Participants assigned to Group B crossed-over to received Vigil monotherapy at a concentration of 1 X 10e6 cells//dose via intradermal injection every 21 days following End of Treatment assessment.

Participants received up to 12 doses of Vigil depending upon the quantity of Vigil manufactured.

Cross-over to Vigil Alone

Participants randomized to Group A received oral temozolomide 100 mg/m\^2 daily (Days 1-5), total dose 500 mg/m\^2/cycle) and oral irinotecan 50 mg/m\^2 daily (Days 1-5, total dose 250 mg/m\^2/cycle). Vigil immunotherapy was administered at a concentration of 1 X 10e6 cells/dose given via intradermal injection on Day 15 of each cycle. 1 cycle = 21 days

Participants continued treatment for a maximum of 12 cycles, or until disease progression, unacceptable toxicity, withdrawal of consent or other criterion is met for discontinuation from study.

Participants randomized to Group B received oral temozolomide 100 mg/m\^2 daily (Days 1-5), total dose 500 mg/m\^2/cycle) and oral irinotecan 50 mg/m\^2 daily (Days 1-5, total dose 250 mg/m\^2/cycle).

1 cycle = 21 days

Participants continued treatment for a maximum of 12 cycles, or until disease progression, unacceptable toxicity, withdrawal of consent or other criterion is met for discontinuation from study.

Total

Age, Categorical

Ethnicity (NIH/OMB)

Race (NIH/OMB)

United States

Region of Enrollment

An assessment of Performance Status (PS) on the Karnofsky or Lansky scale is standard way of measuring the ability of cancer patients to perform ordinary tasks. The PS scores range from 0 to 100. A higher score means the patient is better able to carry out daily activities. The assessment is made by an investigator during the physical exam of the subject.

Baseline Performance Status

Only 1 subject randomized to Group B was eligible to Cross-over to receive Vigil.

Early termination of trial leading to small numbers of subjects analyzed. Technical problems with measurement leading to unreliable or uninterpretable data.

Clinical and Regulatory Operations

Participants randomized to Group B received oral temozolomide 100 mg/m2 daily (Days 1-5), total dose 500 mg/m2/cycle) and oral irinotecan 50 mg/m2 daily (Days 1-5, total dose 250 mg/m2/cycle). 1 cycle = 21 days

Participants continued treatment for a maximum of 12 cycles, or until disease progression, unacceptable toxicity, withdrawal of consent or other criterion is met for discontinuation from study.

PFS is not adequately assessable for difference between cohorts given only 5 participants were enrolled and received treatment.

Progression Free Survival (PFS)

OS is not adequately assessable for difference between cohorts given only 5 participants were enrolled and received treatment.

Overall Survival (OS)

No subjects on trial achieved a partial or complete response, therefore the ORR was not determined.

Overall Response Rate (ORR)

Participants who underwent tissue procurement and the processed tissue samples were successfully shipped to Gradalis whereby Vigil production was attempted.

Total Number of Tissue Procurements

All enrolled subjects who completed tissue procurement and the tissue was received by Gradalis for Vigil Manufacture. Any subjects whose tissue was not submitted to Gradalis was excluded in the analysis.

Vigil Manufacture Success Rate: Number of Participants Eligible for Treatment on the Main Study.

Main Study

Group B Crossover to Vigil Alone

Melanoma

Neuroblastoma

Antibodies

Immunoglobulins

Those who meet eligibility criteria and consent to participate in the study.

Victor Santana, MD

Hu14.18K322A is a monoclonal antibody developed at St. Jude Children's Research Hospital (SJCRH) that is made to bind to cancer cells that have a molecule called GD2 on their surface. Sometimes the human body will make an antibody to the therapeutic antibody (like hu14.18K322A) that is being given for treatment. These are called human anti-human antibodies (HAHA). When testing for HAHA in a previous cohort of patients who received hu14.18K322A, it was found that some patients tested positive for high levels of an antibody before receiving hu14.18K322A or any other anti-GD2 antibody. In this study, investigators would like to know more about the nature of this pretreatment antibody, how often is it present, and if in the laboratory it increases the killing of tumor cells.

OBJECTIVES:

* To determine whether pretreatment anti-therapeutic antibodies (PATA) represent antibodies reactive against an epitope (allotypic determinant) found on the anti-GD2 antibody hu14.18K322A
* To determine if PATA increases the anti-tumor efficacy of anti-GD2 antibodies in vitro

In the proposed study, investigators will seek to determine the nature of this antibody that is being detected in the HAHA test for this group of patients, and if, in the laboratory, it increases the killing of tumor cells, accounting for the observation that some the patients who tested positive may have an improved outcome.

The study will analyze DNA from blood samples of SJCRH patients treated with hu14.18K322A anti-GD2 antibody. Serological studies and confirmatory genotyping studies will be performed in a laboratory at the University of Wisconsin.

DNA from tumor tissue. Blood serum samples.

Pretreatment Anti-Therapeutic Antibodies (PATA) in Patients Treated With hu14.18K322A Antibody

Characterization of Pretreatment Anti-Therapeutic Antibodies (PATA) in Patients Treated With hu14.18K322A Antibody

Objective: To determine whether pretreatment anti-therapeutic antibodies (PATA) represent antibodies reactive against an epitope (allotypic determinant) found on the anti-GD2 antibody hu14.18K322A

Objective: To determine if PATA increases the anti-tumor efficacy of anti-GD2 antibodies in vitro

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Stereotactic Body Radiotherapy (SBRT) for Pulmonary Metastases in Ewing Sarcoma, Rhabdomyosarcoma, and Wilms Tumors	NCT02581384	Ewing Sarcoma Rhabdomyosarcom... Wilms Tumor Osteosarcoma Non-Rhabdomyosa... Renal Tumor Rhabdoid Tumor Clear Cell Rena... Sarcoma Sarcoma, Ewing Soft Tissue Sar...	Stereotactic Bo...	- 21 Years	Dana-Farber Cancer Institute
A Trial For Participants With Ewing's Sarcoma Treated With Vigil in Combination With Irinotecan and Temozolomide	NCT03495921	Ewing Sarcoma Ewing Family of... Ewing's Tumor M... Ewing's Sarcoma... Ewing's Tumor R... Rare Diseases Sarcoma Neoplasms, Conn... Neoplasms by Hi... Neoplasms, Bone... Neoplasms, Conn... Sarcoma, Ewing Neoplasms	Vigil Irinotecan Temozolomide	2 Years -	Gradalis, Inc.
Stereotactic Body Radiotherapy (SBRT) for Pulmonary Metastases in Ewing Sarcoma, Rhabdomyosarcoma, and Wilms Tumors	NCT02581384	Ewing Sarcoma Rhabdomyosarcom... Wilms Tumor Osteosarcoma Non-Rhabdomyosa... Renal Tumor Rhabdoid Tumor Clear Cell Rena... Sarcoma Sarcoma, Ewing Soft Tissue Sar...	Stereotactic Bo...	- 21 Years	Dana-Farber Cancer Institute
Pretreatment Anti-Therapeutic Antibodies (PATA) in Patients Treated With hu14.18K322A Antibody	NCT02159443	Ewing Family of... Melanoma Neuroblastoma Osteosarcoma		-	St. Jude Children's Research Hospital
Pretreatment Anti-Therapeutic Antibodies (PATA) in Patients Treated With hu14.18K322A Antibody	NCT02159443	Ewing Family of... Melanoma Neuroblastoma Osteosarcoma		-	St. Jude Children's Research Hospital

Spots Global Cancer Trial Database for ewing family of tumors