Ignite Creation Date:
2025-12-24 @ 11:48 AM
Ignite Modification Date:
2026-01-01 @ 8:21 PM
Study NCT ID:
NCT01453361
Status:
TERMINATED
Last Update Posted:
2018-05-24
First Post:
2011-08-10
Is Gene Therapy:
True
Has Adverse Events:
True
Brief Title:
Phase II FANG™ in Advanced Melanoma
Sponsor:
Organization:
Raw JSON
{'hasResults': True, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'conditionBrowseModule': {'meshes': [{'id': 'D008545', 'term': 'Melanoma'}], 'ancestors': [{'id': 'D018358', 'term': 'Neuroendocrine Tumors'}, {'id': 'D017599', 'term': 'Neuroectodermal Tumors'}, {'id': 'D009373', 'term': 'Neoplasms, Germ Cell and Embryonal'}, {'id': 'D009370', 'term': 'Neoplasms by Histologic Type'}, {'id': 'D009369', 'term': 'Neoplasms'}, {'id': 'D009380', 'term': 'Neoplasms, Nerve Tissue'}, {'id': 'D018326', 'term': 'Nevi and Melanomas'}, {'id': 'D012878', 'term': 'Skin Neoplasms'}, {'id': 'D009371', 'term': 'Neoplasms by Site'}, {'id': 'D012871', 'term': 'Skin Diseases'}, {'id': 'D017437', 'term': 'Skin and Connective Tissue Diseases'}]}}, 'resultsSection': {'moreInfoModule': {'pointOfContact': {'email': 'info@gradalisinc.com', 'phone': '2144428124', 'title': 'Director of Clinical Trials', 'organization': 'Gradalis, Inc.'}, 'certainAgreement': {'piSponsorEmployee': False, 'restrictiveAgreement': True}}, 'adverseEventsModule': {'eventGroups': [{'id': 'EG000', 'title': 'Vigil™ Vaccine', 'description': 'Autologous Vigil™ vaccine will be supplied by Gradalis, Inc. Patients will receive 1 x 10e7 cells via intradermal injection one day each month for a minimum maximum of 12 doses as long as subject is clinically stable.\n\nVigil™ Vaccine', 'otherNumAtRisk': 18, 'deathsNumAtRisk': 18, 'otherNumAffected': 3, 'seriousNumAtRisk': 18, 'deathsNumAffected': 15, 'seriousNumAffected': 3}], 'otherEvents': [{'term': 'Injection Site Reaction', 'stats': [{'groupId': 'EG000', 'numAtRisk': 18, 'numEvents': 9, 'numAffected': 3}], 'organSystem': 'General disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'CTCAE (4.0)'}], 'seriousEvents': [{'term': 'Soft Tissue Infection', 'notes': 'Infection of Left Great Toe', 'stats': [{'groupId': 'EG000', 'numAtRisk': 18, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'Infections and infestations', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'CTCAE (4.0)'}, {'term': 'Skin Ulceration', 'notes': 'Hemorrhage from tumor nodule', 'stats': [{'groupId': 'EG000', 'numAtRisk': 18, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'Skin and subcutaneous tissue disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'CTCAE (4.0)'}, {'term': 'Tumor Pain', 'notes': 'Sacral Nerve Compression secondary to Metastatic Melanoma', 'stats': [{'groupId': 'EG000', 'numAtRisk': 18, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'Neoplasms benign, malignant and unspecified (incl cysts and polyps)', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'CTCAE (4.0)'}, {'term': 'Abdominal Hernia', 'notes': 'Incarcerated Abdominal Hernia', 'stats': [{'groupId': 'EG000', 'numAtRisk': 18, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'Gastrointestinal disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'CTCAE (4.0)'}], 'frequencyThreshold': '5'}, 'outcomeMeasuresModule': {'outcomeMeasures': [{'type': 'PRIMARY', 'title': 'Enzyme-Linked ImmunoSorbent Spot (ELISPOT)', 'denoms': [{'units': 'Participants', 'counts': [{'value': '18', 'groupId': 'OG000'}]}], 'groups': [{'id': 'OG000', 'title': 'Vigil™ Vaccine', 'description': 'Autologous Vigil™ vaccine will be supplied by Gradalis, Inc. Patients will receive 1 x 10e7 cells via intradermal injection one day each month for a minimum maximum of 12 doses as long as subject is clinically stable.\n\nVigil™ Vaccine'}], 'classes': [{'title': 'ELISPOT Positive After 12 months', 'categories': [{'measurements': [{'value': '7', 'groupId': 'OG000'}]}]}, {'title': 'ELISPOT Negative After 12 months', 'categories': [{'measurements': [{'value': '0', 'groupId': 'OG000'}]}]}, {'title': 'Not Done/Died immediately after Baseline', 'categories': [{'measurements': [{'value': '1', 'groupId': 'OG000'}]}]}, {'title': 'Not Done/Screen-Failed', 'categories': [{'measurements': [{'value': '10', 'groupId': 'OG000'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'timeFrame': 'Baseline, End of Treatment (30 days after last dose) up to 12 months', 'description': 'To determine if subjects will have a positive (defined as \\>10 ELISPOTS from baseline) immune response to Vigil. Blood was collected to compare ELISPOT results from baseline until EOT (30 days after last dose).', 'unitOfMeasure': 'Participants', 'reportingStatus': 'POSTED', 'populationDescription': '18 subjects were consented but only 8 subjects were administered Vigil treatment (10 screen-failed). 7 completed treatment (ELISPOT done) while 1 subject died soon after baseline (ELISPOT not done). After 12 months, 7 subjects had positive ELISPOT response. Statistical analysis was not done. This study was terminated.'}, {'type': 'SECONDARY', 'title': 'Number of Alive Subjects', 'denoms': [{'units': 'Participants', 'counts': [{'value': '18', 'groupId': 'OG000'}]}], 'groups': [{'id': 'OG000', 'title': 'Vigil™ Vaccine', 'description': 'Autologous Vigil™ vaccine will be supplied by Gradalis, Inc. Patients will receive 1 x 10e7 cells via intradermal injection one day each month for a minimum maximum of 12 doses as long as subject is clinically stable.\n\nVigil™ Vaccine'}], 'classes': [{'title': 'Alive Subjects After 3 years', 'categories': [{'measurements': [{'value': '1', 'groupId': 'OG000'}]}]}, {'title': 'Dead Subjects After 3 years', 'categories': [{'measurements': [{'value': '7', 'groupId': 'OG000'}]}]}, {'title': 'Screen-Failed', 'categories': [{'measurements': [{'value': '10', 'groupId': 'OG000'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'timeFrame': '3 years', 'description': 'The survival status in patients with stages IIIc and IV melanoma treated with Vigil™ vaccine was determined by following these patients up to 3 years.', 'unitOfMeasure': 'Participants', 'reportingStatus': 'POSTED', 'populationDescription': '18 subjects were consented but only 8 were administered Vigil treatment (10 screen-failed). These 8 subjects were followed for survival up to 3 years after Vigil treatment.'}]}, 'participantFlowModule': {'groups': [{'id': 'FG000', 'title': 'Vigil™ Vaccine', 'description': 'Autologous Vigil™ vaccine will be supplied by Gradalis, Inc. Patients will receive 1 x 10e7 cells via intradermal injection one day each month for a minimum maximum of 12 doses as long as subject is clinically stable.\n\nVigil™ Vaccine'}], 'periods': [{'title': 'Overall Study', 'milestones': [{'type': 'STARTED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '18'}]}, {'type': 'COMPLETED', 'comment': '"Completed" means subject had successful Vigil manufacturing and had been given all the doses.', 'achievements': [{'groupId': 'FG000', 'numSubjects': '2'}]}, {'type': 'NOT COMPLETED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '16'}]}], 'dropWithdraws': [{'type': 'Disease Progression', 'reasons': [{'groupId': 'FG000', 'numSubjects': '6'}]}, {'type': 'Screen-Failures', 'reasons': [{'groupId': 'FG000', 'numSubjects': '10'}]}]}], 'recruitmentDetails': 'This study recruited patients with Stages IIIc and IV melanoma.', 'preAssignmentDetails': '18 were enrolled but 10 screen-failed so only 8 proceeded with the single group assignment (Vigil treatment).'}, 'baselineCharacteristicsModule': {'denoms': [{'units': 'Participants', 'counts': [{'value': '18', 'groupId': 'BG000'}]}], 'groups': [{'id': 'BG000', 'title': 'Vigil™ Vaccine', 'description': 'Autologous Vigil™ vaccine will be supplied by Gradalis, Inc. Patients will receive 1 x 10e7 cells via intradermal injection one day each month for a minimum maximum of 12 doses as long as subject is clinically stable.\n\nVigil™ Vaccine'}], 'measures': [{'title': 'Age, Customized', 'classes': [{'title': 'Age', 'categories': [{'title': '0-15 Years', 'measurements': [{'value': '0', 'groupId': 'BG000'}]}, {'title': '16-64 Years', 'measurements': [{'value': '9', 'groupId': 'BG000'}]}, {'title': '65 and Older Years', 'measurements': [{'value': '9', 'groupId': 'BG000'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'unitOfMeasure': 'Participants'}, {'title': 'Sex: Female, Male', 'classes': [{'categories': [{'title': 'Female', 'measurements': [{'value': '6', 'groupId': 'BG000'}]}, {'title': 'Male', 'measurements': [{'value': '12', 'groupId': 'BG000'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'unitOfMeasure': 'Participants'}, {'title': 'Race/Ethnicity, Customized', 'classes': [{'categories': [{'title': 'White/Caucasian', 'measurements': [{'value': '18', 'groupId': 'BG000'}]}, {'title': 'Black/African American', 'measurements': [{'value': '0', 'groupId': 'BG000'}]}, {'title': 'Asian', 'measurements': [{'value': '0', 'groupId': 'BG000'}]}, {'title': 'Hispanic', 'measurements': [{'value': '0', 'groupId': 'BG000'}]}, {'title': 'Other', 'measurements': [{'value': '0', 'groupId': 'BG000'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'unitOfMeasure': 'Participants'}]}}, 'protocolSection': {'designModule': {'phases': ['PHASE2'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'NA', 'maskingInfo': {'masking': 'NONE'}, 'primaryPurpose': 'TREATMENT', 'interventionModel': 'SINGLE_GROUP'}, 'enrollmentInfo': {'type': 'ACTUAL', 'count': 18}}, 'statusModule': {'whyStopped': 'Business Decision to pursue other indications', 'overallStatus': 'TERMINATED', 'startDateStruct': {'date': '2011-10'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2018-05', 'completionDateStruct': {'date': '2016-03-22', 'type': 'ACTUAL'}, 'lastUpdateSubmitDate': '2018-05-21', 'studyFirstSubmitDate': '2011-08-10', 'resultsFirstSubmitDate': '2018-02-15', 'studyFirstSubmitQcDate': '2011-10-14', 'lastUpdatePostDateStruct': {'date': '2018-05-24', 'type': 'ACTUAL'}, 'resultsFirstSubmitQcDate': '2018-05-08', 'studyFirstPostDateStruct': {'date': '2011-10-17', 'type': 'ESTIMATED'}, 'resultsFirstPostDateStruct': {'date': '2018-05-11', 'type': 'ACTUAL'}, 'primaryCompletionDateStruct': {'date': '2016-03-22', 'type': 'ACTUAL'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'Enzyme-Linked ImmunoSorbent Spot (ELISPOT)', 'timeFrame': 'Baseline, End of Treatment (30 days after last dose) up to 12 months', 'description': 'To determine if subjects will have a positive (defined as \\>10 ELISPOTS from baseline) immune response to Vigil. Blood was collected to compare ELISPOT results from baseline until EOT (30 days after last dose).'}], 'secondaryOutcomes': [{'measure': 'Number of Alive Subjects', 'timeFrame': '3 years', 'description': 'The survival status in patients with stages IIIc and IV melanoma treated with Vigil™ vaccine was determined by following these patients up to 3 years.'}]}, 'oversightModule': {'oversightHasDmc': True}, 'conditionsModule': {'keywords': ['FANG', 'Melanoma', 'Vigil'], 'conditions': ['Advanced Melanoma']}, 'referencesModule': {'references': [{'pmid': '21208907', 'type': 'BACKGROUND', 'citation': 'Olivares J, Kumar P, Yu Y, Maples PB, Senzer N, Bedell C, Barve M, Tong A, Pappen BO, Kuhn J, Magee M, Wallraven G, Nemunaitis J. Phase I trial of TGF-beta 2 antisense GM-CSF gene-modified autologous tumor cell (TAG) vaccine. Clin Cancer Res. 2011 Jan 1;17(1):183-92. doi: 10.1158/1078-0432.CCR-10-2195.'}, {'type': 'BACKGROUND', 'citation': 'Maples PB, Kumar P, Yu Y, Wang Z, Jay CM, Pappen BO, Rao DD, Kuhn J, Nemunaitis J, Senzer N: FANG Vaccine: Autologous Tumor Cell Vaccine Genetically Modified to Express GM-CSF and Block Production of Furin. BioProcessing Journal 2010; 8(4):4-14.'}, {'pmid': '22186789', 'type': 'BACKGROUND', 'citation': '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.'}], 'seeAlsoLinks': [{'url': 'http://www.oatext.com/pdf/BGG-1-116.pdf', 'label': 'Follow-up of bi-shRNAfurin /GM-CSF Engineered Autologous Tumor Cell (EATC) Immunotherapy Vigil in patients with advanced melanoma'}]}, 'descriptionModule': {'briefSummary': 'Preliminary studies with a variety of vaccines suggest target accessibility (potential immunogenicity) in a variety of solid tumors to immune directed approaches. In an effort to overcome limitations of immunostimulatory cancer vaccines, the investigators have designed a novel autologous vaccine to address inability to fully identify cancer associated antigens, antigen recognition by the immune system (i.e. antigen to immunogen), effector potency, and cancer-induced resistance. In an effort to overcome limitations of immunostimulatory cancer vaccines, the investigators designed a novel dual-modulatory autologous whole cell vaccine, Vigil™ (bi-shRNA furin and GMCSF Autologous Tumor Cell Vaccine), incorporating the rhGMCSF (recombinant human GMCSF) transgene and the bifunctional shRNAfurin (to block proprotein conversion to active TGFb1 and b2) to 1) address the inability to fully identify cancer associated antigens, 2) effect antigen recognition by the immune system (i.e. antigen to immunogen), 3) enhance effector potency, and 4) subvert endogenous cancer-induced immune resistance. The investigators have also completed the Phase I assessment of Vigil™ vaccine in 27 advanced solid tumor patients (1.0 x 10e7 or 2.5 x 10e7 cells/injection/month for a maximum of 12 vaccinations) who have not experienced any significant adverse effects following 131 vaccinations, including 4 patients with melanoma. Plasmid functionality, immune biomarker response, and preliminary evidence of anticancer activity have been observed. This is a Phase II study of intradermal autologous Vigil™ cancer vaccine (1.0 x 10e7 cells/injection; maximum of 12 vaccinations) in patients with stages IIIc and IV melanoma with biopsy accessible lesions to document blood and intratumoral immune responses and assess correlation with survival.'}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['ADULT', 'OLDER_ADULT'], 'minimumAge': '18 Years', 'healthyVolunteers': False, 'eligibilityCriteria': 'Inclusion Criteria:\n\n1. Histologically confirmed Stages IIIc and IV melanoma.\n2. Has been informed of all alternative ≥ second-line therapies that are the current standard of care. If no conventional frontline therapy indicated or acceptable by patient, patient may participate after review by sponsor.\n3. Clinically (medically) indicated procedure (i.e. biopsy of lesions of recurrent disease, palliative management via resection, thoracentesis, etc.) to collect viable tumor in sufficient quantity ("golf ball size" estimated weight \\~ 30 grams, pleural and/or ascites fluid estimated volume ≥ 500mL) for vaccine processing.\n4. Recovered to ≤ Grade 1 (excluding alopecia) from all clinically relevant toxicities related to prior therapies.\n5. Patients will be allowed to participate following single prior CNS treatment with stereotactic radiotherapy whole brain irradiation and stable without steroid requirement for ≥2 months or following ≥2 prior CNS treatments with stereotactic radiotherapy whole brain irradiation and stable without steroid requirement for ≥4 months.\n6. Patients must be off all "statin" drugs for ≥ 2 weeks prior to initiation of therapy.\n7. Age ≥18 years.\n8. ECOG performance status (PS) 0-1.\n9. Estimated \\>4 month survival probability.\n10. Normal organ and marrow function as defined below:\n\n Absolute granulocyte count ≥1,500/mm3 Absolute lymphocyte count ≥500/mm3 Platelets ≥100,000/mm3 Total bilirubin ≤2 mg/dL AST(SGOT)/ALT(SGPT) ≤2x institutional upper limit of normal Creatinine \\<1.5 mg/dL\n11. Ability to understand and the willingness to sign a written informed consent document.\n12. Negative pregnancy test.\n\nExclusion Criteria:\n\n1. Surgery involving general anesthesia, chemotherapy, radiotherapy, steroid therapy, or immunotherapy within 4 weeks prior to entering the study. Collection of lumenal tissue must be avoided.\n2. Patient must not have received any other investigational agents within 30 days prior to study entry.\n3. Patients with known active or symptomatic brain metastases.\n4. Patients with compromised pulmonary disease.\n5. Short term (\\<30 days) concurrent systemic steroids ≤ 0.25 mg/kg prednisone per day (maximum 7.5 mg/day) and bronchodilators (inhaled steroids) are permitted; other steroid regimens and/or immunosuppressives are excluded. Patients requiring steroids following previous CNS radiation for metastatic disease are excluded.\n6. Prior splenectomy.\n7. Prior malignancy (excluding nonmelanoma carcinomas of the skin) unless in remission for 2 years.\n8. Kaposi\'s Sarcoma.\n9. Uncontrolled intercurrent illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.\n10. Patients who are pregnant or nursing.\n11. Patients with known HIV.\n12. Patients with chronic Hepatitis B and C infection.\n13. Patients with uncontrolled autoimmune diseases.'}, 'identificationModule': {'nctId': 'NCT01453361', 'briefTitle': 'Phase II FANG™ in Advanced Melanoma', 'organization': {'class': 'INDUSTRY', 'fullName': 'Gradalis, Inc.'}, 'officialTitle': 'Phase II Trial of FANG™ Autologous Tumor Cell Vaccine in Advanced Melanoma', 'orgStudyIdInfo': {'id': 'CL-PTL 114'}}, 'armsInterventionsModule': {'armGroups': [{'type': 'EXPERIMENTAL', 'label': 'Vigil™ Vaccine', 'description': 'Autologous Vigil™ vaccine will be supplied by Gradalis, Inc. Patients will receive 1 x 10e7 cells via intradermal injection one day each month for a minimum maximum of 12 doses as long as subject is clinically stable.', 'interventionNames': ['Biological: Vigil™ Vaccine']}], 'interventions': [{'name': 'Vigil™ Vaccine', 'type': 'BIOLOGICAL', 'otherNames': ['formerly known as FANG™'], 'armGroupLabels': ['Vigil™ Vaccine']}]}, 'contactsLocationsModule': {'locations': [{'zip': '75230', 'city': 'Dallas', 'state': 'Texas', 'country': 'United States', 'facility': 'Mary Crowley Cancer Research Centers', 'geoPoint': {'lat': 32.78306, 'lon': -96.80667}}], 'overallOfficials': [{'name': 'Minal Barve, MD', 'role': 'PRINCIPAL_INVESTIGATOR', 'affiliation': 'Mary Crowley Cancer Research Center'}]}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'Gradalis, Inc.', 'class': 'INDUSTRY'}, 'responsibleParty': {'type': 'SPONSOR'}}}}