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Ewing SarcomaPhase 3VITANCT03495921

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

A Phase 3 study testing Vigil, Irinotecan and Temozolomide in people with Ewing Sarcoma and Ewing Family of Tumors, run by Gradalis, Inc. at 15 sites in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial summary

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. Read more about this study

Who is it for?
Ages 2 years and older
What is being tested?
Vigil, Irinotecan and Temozolomide
Could I receive a placebo?
No, everyone receives an active treatment
How many people
32 participants
Where
15 sitesUnited States
Study dates
21 Aug 2018to 20 Jan 2022
Phase
Phase 3
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 2 years and older
  • All sexes
  • No healthy volunteers
  • Child, Adult, Older adult

Who may be able to join

  • Group B subjects will be eligible for cross-over, if they meet all of the following criteria:
  • Evidence of radiologic disease progression by RECIST 1.1 after enrollment into Group B.
  • Successful manufacturing of at least 4 vials of Vigil.
  • Karnofsky performance status (KPS) / Lansky performance status (LS) ≥70%.
  • Normal organ and marrow function as defined below:
  • Absolute granulocyte count ≥1,000/mm3 Absolute lymphocyte count ≥400/mm3 Platelets ≥75,000/mm3 Total bilirubin ≤ institutional upper limit of normal AST(SGOT)/ALT(SGPT) ≤2x institutional upper limit of normal Creatinine <1.5 mg/dL
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  • documented Gilbert's syndrome may be considered after medical monitor review.
  • Subject has recovered to CTCAE Grade 1 (except for parameters noted in Item 4, above) or better from all adverse events associated with prior therapy or surgery. Preexisting motor, sensory neurologic pathology or symptoms, or dermatologic toxicities must be recovered to CTCAE Grade 2 or better.
  • If female of childbearing potential, has a negative urine or serum pregnancy test. If the urine test is positive or cannot be confirmed as negative, a negative serum test will be required for study entry.
  • Ability to understand and the willingness to sign a written informed protocol specific consent or a parental/guardian informed consent and pediatric assent when appropriate.

Who cannot join

  • In addition to the Procurement and Study Enrollment exclusion criteria, Subjects will not be eligible for cross-over if meeting any of the following criteria:
  • With the exception of irinotecan and temozolomide while on study, any anti-neoplastic therapy between tissue procurement for Vigil manufacture and start of study therapy.
  • Live vaccine used for the prevention of infectious disease administered < 30 days prior to the start of study therapy.

Trial locations and contacts

15 sites in 1 country.

15 sites in 1 country

United States15 sites

  • Dana-Farber/Boston Children's Cancer and Blood Disorders

    Boston, Massachusetts, 02215

  • Cincinnati Children's Hospital Medical Center

    Cincinnati, Ohio, 45229

  • Cleveland Clinic

    Cleveland, Ohio, 44195

  • Texas Oncology - Pediatrics

    Dallas, Texas, 75230

  • Duke Children's Hospital and Health Center; Duke Cancer Institute

    Durham, North Carolina, 27710

  • Cook Children's Medical Center

    Fort Worth, Texas, 76104

  • Mayo Clinic Florida

    Jacksonville, Florida, 32224

  • Arkansas Children's Hospital

    Little Rock, Arkansas, 72202

  • Southern California Permanente Medical Group

    Los Angeles, California, 90027

  • Nicklaus Children's Hospital

    Miami, Florida, 33155

  • Memorial Sloan Kettering Cancer Center

    New York, New York, 10065

  • Nebraska Methodist Hospital

    Omaha, Nebraska, 68114

  • Fox Chase Cancer Center

    Philadelphia, Pennsylvania, 19111

  • Seattle Cancer Care Alliance

    Seattle, Washington, 98109

  • Washington University Siteman Cancer Center

    St Louis, Missouri, 63110

Other trials in United States

About this study

Official title: 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

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?".

Read the detailed description

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.

Being tested
Vigil, Irinotecan, Temozolomide
Keywords
ESFT, Immunotherapy, Phase 3, irinotecan, temozolomide, First Relapse, Second Line, Vigil, vaccine, orphan drug, soft bone, pediatric, FLI, EWS, Molecular Mechanisms of Pharmacological Action, Antineoplastic Agents
Medical subject headings
Sarcoma, Ewing, Neuroectodermal Tumors, Primitive, Peripheral, Rare Diseases, Sarcoma, Neoplasms, Connective and Soft Tissue, Neoplasms by Histologic Type, Neoplasms, Bone Tissue, Neoplasms, Connective Tissue

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • VigilBiological

    Also called Bi-shRNAfurin and GMCSF Augmented Autologous Tumor Cell Immunotherapy, FANG vaccine

    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.

  • IrinotecanDrug

    Also called Camptosar, Camptothecin-11, CPT-11

    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.

  • TemozolomideDrug

    Also called Temodar

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

Study groups in NCT03495921
Study groupRoleWhat they receive
Group A: Vigil + Irinotecan and TemozolomideExperimentalParticipants 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.
Receives: Biological: Vigil; Drug: Irinotecan; Drug: Temozolomide
Group B: Irinotecan and TemozolomideActive comparatorParticipants 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.
Receives: Drug: Irinotecan; Drug: Temozolomide
Cross-Over: Vigil monotherapyOtherParticipants 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
Receives: Biological: Vigil

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Progression Free Survival (PFS)

    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.

    Measured: From date of randomization until the date of first documented progression (assessed up to 3 years).

Secondary outcomes (3)

  1. Overall Survival (OS)

    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.

    Measured: From date of randomization until date of death from any cause, whichever came first (assessed up to 3 years).

  2. Overall Response Rate (ORR)

    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.

    Measured: 6 months after treatment with Vigil.

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

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

    Measured: From manufacturing start date until 4 weeks post manufacturing for each tissue procurement (assessed up to 17 months).

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted12 Apr 2018
  2. Study start21 Aug 2018
  3. Primary completion20 Jan 2022
  4. Study completion20 Jan 2022

Why it stopped: Slow accrual and as a result, a strategic business decision was made to terminate enrollment.

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Model description
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.
Masking
None (open label)
Enrolment
32 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03495921
Sponsor's protocol ID
CL-PTL-130
Acronym
VITA
Status last verified
Apr 2023
First submitted
15 Feb 2018
Last updated
26 Apr 2023
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No
Expanded access
Available

Publications

  • Ghisoli M, Rutledge M, Stephens PJ, Mennel R, Barve M, Manley M, Oliai BR, Murphy KM, Manning L, Gutierrez B, Rangadass P, Walker A, Wang Z, Rao D, Adams N, Wallraven G, Senzer N, Nemunaitis J. Case Report: Immune-mediated Complete Response in a Patient With Recurrent Advanced Ewing Sarcoma (EWS) After Vigil Immunotherapy. J Pediatr Hematol Oncol. 2017 May;39(4):e183-e186. doi: 10.1097/MPH.0000000000000822.

    PubMed 28338569

  • Ghisoli M, Barve M, Mennel R, Lenarsky C, Horvath S, Wallraven G, Pappen BO, Whiting S, Rao D, Senzer N, Nemunaitis J. Three-year Follow up of GMCSF/bi-shRNA(furin) DNA-transfected Autologous Tumor Immunotherapy (Vigil) in Metastatic Advanced Ewing's Sarcoma. Mol Ther. 2016 Aug;24(8):1478-83. doi: 10.1038/mt.2016.86. Epub 2016 Apr 25.

    PubMed 27109631

  • Ghisoli M, Barve M, Schneider R, Mennel R, Lenarsky C, Wallraven G, Pappen BO, LaNoue J, Kumar P, Nemunaitis D, Roth A, Nemunaitis J, Whiting S, Senzer N, Fletcher FA, Nemunaitis J. Pilot Trial of FANG Immunotherapy in Ewing's Sarcoma. Mol Ther. 2015 Jun;23(6):1103-1109. doi: 10.1038/mt.2015.43. Epub 2015 Mar 19.

    PubMed 25917459

  • Senzer N, Barve M, Kuhn J, Melnyk A, Beitsch P, Lazar M, Lifshitz S, Magee M, Oh J, Mill SW, Bedell C, Higgs C, Kumar P, Yu Y, Norvell F, Phalon C, Taquet N, Rao DD, Wang Z, Jay CM, Pappen BO, Wallraven G, Brunicardi FC, Shanahan DM, Maples PB, Nemunaitis J. Phase I trial of "bi-shRNAi(furin)/GMCSF DNA/autologous tumor cell" vaccine (FANG) in advanced cancer. Mol Ther. 2012 Mar;20(3):679-86. doi: 10.1038/mt.2011.269. Epub 2011 Dec 20.

    PubMed 22186789

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Vigil, Irinotecan and Temozolomide in people with Ewing Sarcoma and Ewing Family of Tumors, run by Gradalis, Inc. at 15 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 10 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 26 Apr 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 15 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 26 Apr 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Progression Free Survival (PFS) (time frame: From date of randomization until the date of first documented progression (assessed up to 3 years).). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03495921, which also lists 4 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Apr 2023.

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