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Randomized Phase IIb Trial of Vigil Versus Gemcitabine + Docetaxel for Ewing's Sarcoma

This study is currently recruiting participants. (see Contacts and Locations)
Verified February 2017 by Gradalis, Inc.
Sponsor:
Information provided by (Responsible Party):
Gradalis, Inc.
ClinicalTrials.gov Identifier:
NCT02511132
First received: July 28, 2015
Last updated: February 21, 2017
Last verified: February 2017
  Purpose
This is a multicenter, 1:1 randomized Phase IIb study of intradermal autologous Vigil™ cancer vaccine in patients with metastatic Ewing's sarcoma Family of Tumors (ESFT) refractory or intolerant to at least 2 prior lines of chemotherapy. Patients undergoing a standard surgical procedure (e.g., tumor biopsy or palliative resection) may have tumor tissue harvested for manufacture of investigational product. Patients meeting eligibility criteria will be randomized to receive either (1) intradermal Vigil every 28 days for 4-12 administrations, or (2) gemcitabine 675 mg/m2 IV at 10 mg/m2/min D1 and D8 and docetaxel 75 mg/m2 IV D8 every 21 days. The primary trial objective is to determine the overall survival of patients treated with Vigil™ versus gemcitabine/docetaxel.

Condition Intervention Phase
Ewing's Sarcoma
Biological: Vigil
Drug: gemcitabine and docetaxel
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: No masking
Primary Purpose: Treatment
Official Title: Randomized Phase IIb Trial of Vigil (Bi-shRNAfurin and GMCSF Augmented Autologous Tumor Cell Immunotherapy) Versus Gemcitabine + Docetaxel for Ewing's Sarcoma

Resource links provided by NLM:


Further study details as provided by Gradalis, Inc.:

Primary Outcome Measures:
  • Overall Survival [ Time Frame: 5 years ]

    To determine and compare the overall survival of patients with metastatic Ewing's sarcoma refractory or intolerant to ≥ 2 prior lines of systemic chemotherapy treated with Vigil™ immunotherapy vs. gemcitabine/docetaxel.

    Measureable disease is not a requirement for enrollment onto the trial.



Secondary Outcome Measures:
  • γIFN ELISPOT conversion rate [ Time Frame: 1 year ]
    To determine the IFNγ ELISPOT conversion rate of subjects treated with Vigil™ immunotherapy vs gemcitabine/docetaxel.


Estimated Enrollment: 62
Study Start Date: July 2015
Estimated Study Completion Date: December 2018
Estimated Primary Completion Date: December 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Vigil™
1 x 10e7 cells via intradermal injection every 28 days for a 4 - 12 administrations (depending on the quantity of Vigil™ manufactured from surgical specimens)
Biological: Vigil
Other Names:
  • formerly known as FANG™
  • bi-shRNAfurin and GMCSF Autologous Tumor Cell Immunotherapy
Active Comparator: Chemotherapy
gemcitabine 675 mg/m^2 IV at 10 mg/m^2/min D1 and D8 and docetaxel 75 mg/m^2 IV D8 every 21 days
Drug: gemcitabine and docetaxel
gemcitabine 675 mg/m2 IV at 10 mg/m2/min D1 and D8 and docetaxel 75 mg/m2 IV D8 every 21 days

  Eligibility

Ages Eligible for Study:   2 Years and older   (Child, Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Tissue Procurement Inclusion Criteria:

Patients will be eligible for tissue procurement for the Vigil™ manufacturing process, if they meet all of the following criteria:

  1. Histologically confirmed Ewing's Sarcoma Family of Tumors (ESFT).
  2. Age ≥2 years.
  3. Estimated survival ≥ 6 months.
  4. Evidence of EWS translocation by FISH or RT-PCR.
  5. Metastatic disease
  6. Refractory or intolerant to ≥ 2 lines of systemic chemotherapy.
  7. Planned standard of care surgical procedure (e.g., tumor biopsy or palliative resection or thoracentesis) and expected availability of a cumulative mass of ~10-30 grams tissue ("golf-ball" size) or pleural fluid estimated volume ≥ 500mL (must be primary tap) for immunotherapy manufacture.
  8. Tumor intended for immunotherapy manufacture is not embedded in bone and does not contain luminal tissue (e.g. bowel, ureter, bile duct).
  9. Ability to understand and the willingness to sign a written informed consent document for tissue harvest.

Tissue Procurement Exclusion Criteria:

Patients meeting any of the following criteria are not eligible for tissue procurement for the Vigil™ manufacturing:

  1. Medical condition requiring any form of chronic systemic immunosuppressive therapy (steroid or other) except physiologic replacement doses of hydrocortisone or equivalent (no more than 30 mg hydrocortisone or 10 mg prednisone equivalent daily) for < 30 days duration.
  2. Known history of other malignancy unless having undergone curative intent therapy without evidence of that disease for ≥ 3 years except cutaneous squamous cell and basal cell skin cancer, superficial bladder cancer, in situ cervical cancer or other in situ cancers are allowed if definitively resected.
  3. Brain metastases unless treated with curative intent (gamma knife or surgical resection) and without evidence of progression for ≥ 2 months.
  4. Any documented history of autoimmune disease with exception of Type 1 diabetes on stable insulin regimen, hypothyroidism on stable dose of replacement thyroid medication, vitiligo, or asthma not requiring systemic steroids.
  5. Known history of allergies or sensitivities to gentamicin.
  6. Known hypersensitivity reactions to docetaxel or to other drugs formulated with polysorbate 80 that would preclude treatment with docetaxel.
  7. History of or current evidence of any condition (including medical, psychiatric or substance abuse disorder), therapy, or laboratory abnormality that might confound the results of the study, interfere with the patient's participation for the full duration of the study, or is not in the best interest of the patient to participate, in the opinion of the treating Investigator.
  8. Known HIV or chronic Hepatitis B or C infection.

Study Enrollment Inclusion Criteria:

Patients will be eligible for registration and randomization if they meet all of the following inclusion criteria:

  1. Successful manufacturing of at least 4 vials of Vigil™.
  2. Karnofsky performance status (PS) ≥60%.
  3. Estimated survival ≥ 4 months.
  4. Normal organ and marrow function as defined below:

    Absolute granulocyte count ≥1,500/mm3 Absolute lymphocyte count ≥400/mm3 Platelets ≥100,000/mm3 Total bilirubin ≤ institutional upper limit of normal AST(SGOT)/ALT(SGPT) ≤2x institutional upper limit of normal Creatinine <1.5 mg/dL

  5. Subject has recovered to CTCAE Grade 1 or better from all adverse events associated with prior therapy or surgery. Pre-existing motor or sensory neurologic pathology or symptoms must be recovered to CTCAE Grade > 2 or better.
  6. 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.
  7. Ability to understand and the willingness to sign a written informed protocol specific consent.

Study Enrollment Exclusion Criteria:

Measureable disease is not a requirement for enrollment onto the trial.

In addition to the procurement exclusion criteria, patients will NOT be eligible for study registration and randomization if meeting any of the following criteria:

  1. Any anti-neoplastic therapy between tissue procurement for vaccine manufacture and start of study therapy.
  2. Live vaccine used for the prevention of infectious disease administered < 30 days prior to the start of study therapy.
  3. Post-surgery complication that in the opinion of the treating investigator would interfere with the patient's study participation or make it not in the best interest of the patient to participate.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02511132

Contacts
Contact: Gladice Wallraven 214-442-8124 info@gradalisinc.com

Locations
United States, Arkansas
Arkansas Children's Hospital Recruiting
Little Rock, Arkansas, United States, 72202
Contact: Catherine Redinger, RN    501-364-4290    RedingerCatherineL@uams.edu   
Principal Investigator: Kathleen Neville, MD, MS, MBA         
United States, California
Sarcoma Oncology Research Center Recruiting
Santa Monica, California, United States, 90403
Contact: Victoria S Chua-Alcala    310-552-9999    vchua@sarcomaoncology.com   
Principal Investigator: Sant Chawla, MD         
United States, Florida
Nicklaus Children's Hospital (Miami Children's Health System) Recruiting
Miami, Florida, United States, 33155
Contact: Coraly Diaz-Gamboa    786-324-2853    Coraly.Diaz@mch.com   
Principal Investigator: Guillermo De Angulo, MD         
United States, Missouri
Washington University Medical Center Recruiting
Saint Louis, Missouri, United States, 63110
Contact: Michele Landeau    314-747-9488    landeaum@wustl.edu   
Principal Investigator: Brian A. Van Tine, MD, PhD         
United States, New Hampshire
Dartmouth-Hitchcock Medical Center Recruiting
Lebanon, New Hampshire, United States, 03756
Contact: Jo Strohbehn    603-650-5021    Jo.A.Strohbehn@hitchcock.org   
Principal Investigator: Sara Chaffee, MD         
United States, New York
Children's Hospital at Montefiore Recruiting
Bronx, New York, United States, 10467
Contact: Jonathan Gill, MD    718-741-2342    JGILL@montefiore.org   
Principal Investigator: Jonathan Gill, MD         
Sub-Investigator: Richard Gorlick, MD         
Memorial Sloan Kettering Cancer Center Recruiting
New York, New York, United States, 10065
Contact: Dara Herman       schwamd@mskcc.org   
Contact: Leonard H. Wexler, MD    212-639-7990      
Principal Investigator: Leonard H. Wexler, MD         
United States, Ohio
Cleveland Clinic Children's Recruiting
Cleveland, Ohio, United States, 44195
Contact: Peter Anderson, MD    216-445-4044    andersp@ccf.org   
Contact: Stacey Zahler, DO    216-445-3588    zahlers@ccf.org   
Principal Investigator: Peter Anderson, MD         
Sub-Investigator: Stacey Zahler, DO         
United States, Oregon
Oregon Health and Science University (OHSU) Recruiting
Portland, Oregon, United States, 97239
Contact: Laura Carter    503-418-9354    cartela@ohsu.edu   
Principal Investigator: Lara Davis, MD         
United States, Texas
Mary Crowley Cancer Research Centers Recruiting
Dallas, Texas, United States, 75230
Contact: Referral Office    972-566-3000    referral@marycrowley.org   
Principal Investigator: Minal Barve, MD         
TOPA - Medical City Dallas Pediatric Hematology-Oncology Recruiting
Dallas, Texas, United States, 75230
Contact: Referral Office    972-566-3000    referral@marycrowley.org   
Principal Investigator: Maurizio Ghisoli, MD         
Sponsors and Collaborators
Gradalis, Inc.
Investigators
Study Director: Luisa Manning, MD Gradalis, Inc.
  More Information

Publications:
Responsible Party: Gradalis, Inc.
ClinicalTrials.gov Identifier: NCT02511132     History of Changes
Other Study ID Numbers: CL-PTL-121
Study First Received: July 28, 2015
Last Updated: February 21, 2017

Keywords provided by Gradalis, Inc.:
Ewing's Sarcoma Family of Tumors, ESFT, Sarcoma

Additional relevant MeSH terms:
Sarcoma
Sarcoma, Ewing
Neoplasms, Connective and Soft Tissue
Neoplasms by Histologic Type
Neoplasms
Osteosarcoma
Neoplasms, Bone Tissue
Neoplasms, Connective Tissue
Gemcitabine
Docetaxel
Modafinil
Armodafinil
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Antiviral Agents
Anti-Infective Agents
Enzyme Inhibitors
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Wakefulness-Promoting Agents
Central Nervous System Stimulants
Cytochrome P-450 CYP3A Inducers
Cytochrome P-450 Enzyme Inducers

ClinicalTrials.gov processed this record on March 24, 2017