Neoplasms

All Conditions

Symptoms and General Pathology

Skin and Connective Tissue Diseases

Musculoskeletal Diseases

Rare Diseases

Sarcoma

Recurrence

Sarcoma, Ewing

Neuroectodermal Tumors, Primitive, Peripheral

Neoplasms by Histologic Type

Neoplasms, Connective and Soft Tissue

Neoplasms, Connective Tissue

Neoplasms, Bone Tissue

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Bone Neoplasms

Osteosarcoma

Disease Attributes

Neoplasms, Neuroepithelial

Neoplasms, Germ Cell and Embryonal

Neoplasms, Glandular and Epithelial

Neoplasms, Nerve Tissue

Connective Tissue Diseases

Bone Diseases

Soft Tissue Sarcoma

Ewing Sarcoma

Neuroepithelioma

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

Sex: Female, Male

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

Wounds and Injuries

Nervous System Diseases

Behaviors and Mental Disorders

Neoplasm Metastasis

Fractures, Bone

Pain

Hip Fractures

Pain, Intractable

Femoral Fractures

Hip Injuries

Leg Injuries

Neurologic Manifestations

Quality of Life

Implantation of Y-Strut + cementoplasty in the femoral neck

Implantation

Olivier Pellerin, MD, PhD

Carole Dean, PhD

François Cornelis, MD, PhD

Bone metastases appear in many cancers. They are associated with severe pain that is refractory to standard treatment. Improving the quality of life and better pain relief is therefore an essential goal of the treatment of metastatic disease. The most common site of long bone metastases is the superior femoral epiphysis.

The usual management of patients with bone metastases in the superior femoral epiphysis is based on gamma implant osteosynthesis when there is a known risk of fracture (Mirels score\> 8). Nonetheless this surgery is only accessible to a few patients because of the associated morbidities.

Percutaneous cementoplasty has been developed to treat patients who are not eligible for conventional surgery. It consists in a filling of the bone cavity created by metastasis using an acrylic resin. However, these approaches do not completely prevent the risk of upper femoral epiphyseal fracture due to the low mechanical resistance of the resin to shear movements.

The Y-STRUT® implantable medical device was developed to overcome this risk of superior femoral epiphyseal fracture by the biomechanical strengthening of the proximal femur in addition to cementoplasty. It has been successfully tested in more than 70 patients with cancer but access to reimbursement and the APHP market have been postponed due to lack of sufficient clinical evidence.

The investigators propose this prospective phase 2a study in order to provide evidence of the performance of the Y-STRUT® implant.

The design consists in a multicenter national open simple arm trial.

All eligible patients with a lytic bone metastases of the superior femoral epiphysis will be included.

The main objective of this study is to describe the impact of the Y-STRUT® implant on the quality of life of patients with lytic bone metastases of the femoral neck by comparing quality of life scores before and one month after the intervention of implantation of the implant.

Study of the Impact of the Femoral Implant "Y-strut" on Lytic Bone Metastases of the Femoral Neck (WAZA-ARY)

Prospective Multi-center Study of Impact of Femoral "Y-strut" Implant on Pain and Quality of Life in Patients With Lytic Bone Metastases of the Femoral Neck

Measure of the Quality of Life score using the questionary of quality of life of the European Organization for Research and Treatment of Cancer BM-22.

Patients answer at 22 questions to describe their quality of life during the past week. For each question, patient must choose between 1.not at all, 2.a little, 3.enough, 4.a lot. A global score is calculated by adding the 22 score of each questions. The higher value of this global score represents the better outcome.

Number of AE/SAE imputable to the implatation

Consumption of morphinic mean dose per day during the month after the procedure

Consumption of morphinic mean dose per day during the 2 months after the procedure

Use of Visual Analog Scale (VAS) to evaluate the pain at target site (between 0: no pain to 10: intolerable pain)

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
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.
Study of the Impact of the Femoral Implant "Y-strut" on Lytic Bone Metastases of the Femoral Neck (WAZA-ARY)	NCT03887494	Neoplasms, Bone... Pain, Intractab... Hip Fractures	Implantation	18 Years -	Assistance Publique - Hôpitaux de Paris

Spots Global Cancer Trial Database for neoplasms, bone tissue