- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03842865
Expanded Access of Vigil in Solid Tumors
An Expanded Access Trial of Vigil (Bi-shRNAfurin and GMCSF Augmented Autologous Tumor Cell Immunotherapy) in Advanced Solid Tumors
This is an expanded access study involving an investigational product named Vigil. Vigil is considered immunotherapy. Patients who participated in another clinical trial sponsored by Gradalis, and had Vigil made from their tumor tissue removed from a standard operation, however failed the criteria to enroll in the other clinical trial to receive Vigil are eligible to screen for this expanded access trial to receive the Vigil made from their cancer cells.
In this study, eligible participants will receive intradermal (under the skin) injections of Vigil, once every 4 weeks (28 days) for 1-12 doses, depending on the number of doses that was made from the cancer cells and if the participant is clinically stable. During the treatment portion of the study, in addition to receiving Vigil injections, participants will also have a physical exam, blood collection for routine and research tests, and assessment of medications, adverse events, and performance status information will be collected. Radiological tumor assessments will be performed every 3 months from Cycle 1. Once treatment ends, participants will continue to be seen in the clinic every 3 months for similar assessments until disease progression occurs. After disease progression, participants will be contacted by phone 4 times a year to determine post study treatment and survival status information.
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
This is an Expanded Access trial of Vigil (bi-shRNAfurin and GMCSF Augmented Autologous Tumor Cell Immunotherapy) in Advanced Solid Tumors. Approximately 40 subjects who had tissue procured and Vigil manufactured but fail manufacturing release criteria under a previous Gradalis protocol are considered for this study.
Eligible participants will receive a minimum of 1 and a maximum of 12 doses of Vigil intradermal injections every 4 weeks as monotherapy. Participants will be managed in an outpatient setting. Hematologic function, liver enzymes, renal function and electrolytes will be monitored. Blood for immune function analyses in response to autologous tumor antigens will be collected at screening, Day 1 (prior to Vigil administration) at Cycles 2, 4, and 6, end of treatment (EOT); 3 months after EOT, and every 6 months thereafter for those in response follow up. For subjects with Ewing's sarcoma, blood for ctDNA analysis will be collected at screening, on Day 1 prior to Vigil administration at Cycles 2, 3, 4, and 6, and EOT.
Study Type
Expanded Access Type
- Intermediate-size Population
Contacts and Locations
Study Locations
-
-
Texas
-
Dallas, Texas, United States, 75230
- Texas Oncology - Pediatrics
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
Study Enrollment Inclusion Criteria:
- Histologically confirmed advanced or metastatic non-curable solid tumor.
- Completed manufacture of at least 1 vial of Vigil, but failure of one or more manufacturing release criteria.
- ECOG performance status (PS) 0-1 or 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, Hemoglobin ≥ 8.0 mg/dL, Total bilirubin ≤ institutional upper limit of normal*, AST(SGOT)/ALT(SGPT) ≤2x institutional upper limit of normal, Creatinine <1.5 mg/dL
*documented Gilbert's syndrome may be considered after medical monitor review
- No systemic therapy, immunologic therapy or investigational therapy within 2 weeks and no radiation therapy within 1 week prior to enrollment.
- 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. Pre-existing 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.
Study Enrollment Exclusion Criteria:
- 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.
- 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.
- Receipt of greater than 2 lines of systemic treatment between Vigil manufacture and screening for this protocol.
- Live vaccine used for the prevention of infectious disease administered < 30 days prior to the start of study therapy.
- Post-surgery complication that in the opinion of the treating investigator would interfere with the subject's study participation or make it not in the best interest of the patient to participate.
- Brain metastases unless treated with curative intent (gamma knife or surgical resection) and without evidence of progression for ≥ 2 months.
- 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.
- Known HIV or chronic Hepatitis B or C infection.
- Known history of allergies or sensitivities to gentamicin.
- 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.
Study Plan
How is the study designed?
Collaborators and Investigators
Sponsor
Investigators
- Study Director: John Nemunaitis, MD, Gradalis, Inc.
Publications and helpful links
General 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.
- 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.
- 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.
- 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.
- Oh J, Barve M, Senzer N, Aaron P, Manning L, Wallraven G, Bognar E, Stanbery L, Horvath S, Manley M, Nemunaitis J, Walter A, Rocconi RP. Long-term follow-up of Phase 2A trial results involving advanced ovarian cancer patients treated with Vigil(R) in frontline maintenance. Gynecol Oncol Rep. 2020 Sep 17;34:100648. doi: 10.1016/j.gore.2020.100648. eCollection 2020 Nov. No abstract available. Erratum In: Gynecol Oncol Rep. 2021 Mar 01;36:100740.
- Rocconi RP, Grosen EA, Ghamande SA, Chan JK, Barve MA, Oh J, Tewari D, Morris PC, Stevens EE, Bottsford-Miller JN, Tang M, Aaron P, Stanbery L, Horvath S, Wallraven G, Bognar E, Manning L, Nemunaitis J, Shanahan D, Slomovitz BM, Herzog TJ, Monk BJ, Coleman RL. Gemogenovatucel-T (Vigil) immunotherapy as maintenance in frontline stage III/IV ovarian cancer (VITAL): a randomised, double-blind, placebo-controlled, phase 2b trial. Lancet Oncol. 2020 Dec;21(12):1661-1672. doi: 10.1016/S1470-2045(20)30533-7.
- Oh J, Barve M, Matthews CM, Koon EC, Heffernan TP, Fine B, Grosen E, Bergman MK, Fleming EL, DeMars LR, West L, Spitz DL, Goodman H, Hancock KC, Wallraven G, Kumar P, Bognar E, Manning L, Pappen BO, Adams N, Senzer N, Nemunaitis J. Phase II study of Vigil(R) DNA engineered immunotherapy as maintenance in advanced stage ovarian cancer. Gynecol Oncol. 2016 Dec;143(3):504-510. doi: 10.1016/j.ygyno.2016.09.018. Epub 2016 Sep 24.
Study record dates
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Neoplasms, Connective and Soft Tissue
- Neoplasms by Histologic Type
- Urogenital Neoplasms
- Neoplasms by Site
- Genital Neoplasms, Female
- Uterine Diseases
- Osteosarcoma
- Neoplasms, Bone Tissue
- Neoplasms, Connective Tissue
- Female Urogenital Diseases
- Female Urogenital Diseases and Pregnancy Complications
- Urogenital Diseases
- Genital Diseases
- Genital Diseases, Female
- Neoplasms
- Sarcoma
- Sarcoma, Ewing
- Uterine Neoplasms
- Physiological Effects of Drugs
- Immunologic Factors
- Immunomodulating Agents
Other Study ID Numbers
- CL-PTL-132
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Cervical Cancer
-
University of California, San DiegoWithdrawnCervical Cancer | Cervical Cancer Stage | Cervical Cancer Stage IB2 | Cervical Cancer Stage IB1 | Cervical Cancer Stage I | Cervical Cancer Stage IB | Cervical Cancer Stage II | Cervical Cancer Stage IIa | Cervical Cancer, Stage IIB | Cervical Cancer, Stage III | Cervical Cancer Stage IIIB | Cervical Cancer... and other conditionsUnited States
-
M.D. Anderson Cancer CenterWithdrawnStage IB3 Cervical Cancer FIGO 2018 | Stage II Cervical Cancer FIGO 2018 | Stage IIA Cervical Cancer FIGO 2018 | Stage IIA1 Cervical Cancer FIGO 2018 | Stage IIA2 Cervical Cancer FIGO 2018 | Stage IIB Cervical Cancer FIGO 2018 | Stage III Cervical Cancer FIGO 2018 | Stage IIIA Cervical Cancer FIGO... and other conditions
-
Abramson Cancer Center of the University of PennsylvaniaWithdrawnCervical Cancer | Stage IB Cervical Cancer | Stage IIA Cervical Cancer | Stage IIB Cervical Cancer | Stage III Cervical Cancer | Stage IVA Cervical Cancer
-
National Cancer Institute (NCI)CompletedCervical Adenocarcinoma | Cervical Squamous Cell Carcinoma | Stage IB Cervical Cancer | Stage IIA Cervical Cancer | Stage IIB Cervical Cancer | Stage III Cervical Cancer | Stage IVA Cervical Cancer | Stage IVB Cervical CancerUnited States
-
Mayo ClinicNational Cancer Institute (NCI)RecruitingCervical Adenosquamous Carcinoma | Cervical Squamous Cell Carcinoma, Not Otherwise Specified | Recurrent Cervical Carcinoma | Stage IB3 Cervical Cancer FIGO 2018 | Stage II Cervical Cancer FIGO 2018 | Stage IIA Cervical Cancer FIGO 2018 | Stage IIA1 Cervical Cancer FIGO 2018 | Stage IIA2 Cervical... and other conditionsUnited States
-
M.D. Anderson Cancer CenterNational Cancer Institute (NCI)Active, not recruitingStage IA Cervical Cancer | Stage IB Cervical Cancer | Stage IA1 Cervical Cancer | Stage IA2 Cervical Cancer | Stage IB1 Cervical Cancer | Stage IB2 Cervical Cancer | Stage IB3 Cervical CancerUnited States
-
University of Southern CaliforniaNational Cancer Institute (NCI)CompletedRecurrent Cervical Cancer | Stage IVA Cervical Cancer | Stage IVB Cervical Cancer | Stage IIIA Cervical Cancer | Stage IIIB Cervical CancerUnited States
-
Shanghai First Maternity and Infant HospitalNot yet recruitingCervical Cancer, Stage IIB | Cervical Cancer Stage IIIB | Cervical Cancer Stage IIIA | Cervical Cancer, Stage IVA
-
Gynecologic Oncology GroupNational Cancer Institute (NCI)CompletedCervical Adenocarcinoma | Cervical Squamous Cell Carcinoma | Stage IB Cervical Cancer | Stage IIA Cervical Cancer | Stage IIB Cervical Cancer | Stage III Cervical Cancer | Stage IVA Cervical CancerUnited States
-
Institut de Cancérologie de LorraineCompletedCervical Adenocarcinoma | Stage IB Cervical Cancer | Stage III Cervical Cancer | Stage II Cervical CancerFrance
Clinical Trials on Vigil
-
WALA Heilmittel GmbHNot yet recruiting
-
Genuine Research Center, EgyptChemipharm Pharmaceutical Industries, EgyptCompleted
-
Gradalis, Inc.TerminatedColon CancerUnited States
-
Gradalis, Inc.Roche-GenentechCompletedCervical Cancer | Ovarian Cancer | Uterine Cancer | Advanced Gynecological CancersUnited States
-
Mary Crowley Medical Research CenterAstraZeneca; Gradalis, Inc.CompletedCervical Cancer | Breast Cancer | Ovarian Cancer | Fallopian Tube Cancer | Endometrial Cancer | Primary Peritoneal Carcinoma | Uterine CancerUnited States
-
Gradalis, Inc.Completed
-
Technical University of MunichCephalonWithdrawn
-
Gradalis, Inc.Active, not recruitingOvarian Neoplasms | Ovarian CancerUnited States
-
Gradalis, Inc.CompletedMelanoma | Malignant Melanoma | Melanoma RecurrentUnited States