Ignite Creation Date:
2025-12-24 @ 3:55 PM
Ignite Modification Date:
2026-01-02 @ 2:18 AM
Study NCT ID:
NCT01445392
Status:
TERMINATED
Last Update Posted:
2018-08-03
First Post:
2011-09-30
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
SS1(dsFV)PE38 Plus Pemetrexed and Cisplatin to Treat Malignant Pleural Mesothelioma
Sponsor:
Organization:
Raw JSON
{'hasResults': False, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'conditionBrowseModule': {'meshes': [{'id': 'D008654', 'term': 'Mesothelioma'}, {'id': 'D000086002', 'term': 'Mesothelioma, Malignant'}], 'ancestors': [{'id': 'D000236', 'term': 'Adenoma'}, {'id': 'D009375', 'term': 'Neoplasms, Glandular and Epithelial'}, {'id': 'D009370', 'term': 'Neoplasms by Histologic Type'}, {'id': 'D009369', 'term': 'Neoplasms'}, {'id': 'D018301', 'term': 'Neoplasms, Mesothelial'}, {'id': 'D008175', 'term': 'Lung Neoplasms'}, {'id': 'D012142', 'term': 'Respiratory Tract Neoplasms'}, {'id': 'D013899', 'term': 'Thoracic Neoplasms'}, {'id': 'D009371', 'term': 'Neoplasms by Site'}, {'id': 'D010997', 'term': 'Pleural Neoplasms'}, {'id': 'D008171', 'term': 'Lung Diseases'}, {'id': 'D012140', 'term': 'Respiratory Tract Diseases'}]}, 'interventionBrowseModule': {'meshes': [{'id': 'D000068437', 'term': 'Pemetrexed'}, {'id': 'D002945', 'term': 'Cisplatin'}], 'ancestors': [{'id': 'D006147', 'term': 'Guanine'}, {'id': 'D007042', 'term': 'Hypoxanthines'}, {'id': 'D011688', 'term': 'Purinones'}, {'id': 'D011687', 'term': 'Purines'}, {'id': 'D006574', 'term': 'Heterocyclic Compounds, 2-Ring'}, {'id': 'D000072471', 'term': 'Heterocyclic Compounds, Fused-Ring'}, {'id': 'D006571', 'term': 'Heterocyclic Compounds'}, {'id': 'D005971', 'term': 'Glutamates'}, {'id': 'D024342', 'term': 'Amino Acids, Acidic'}, {'id': 'D000596', 'term': 'Amino Acids'}, {'id': 'D000602', 'term': 'Amino Acids, Peptides, and Proteins'}, {'id': 'D000600', 'term': 'Amino Acids, Dicarboxylic'}, {'id': 'D017606', 'term': 'Chlorine Compounds'}, {'id': 'D007287', 'term': 'Inorganic Chemicals'}, {'id': 'D017672', 'term': 'Nitrogen Compounds'}, {'id': 'D017671', 'term': 'Platinum Compounds'}]}}, 'protocolSection': {'designModule': {'phases': ['PHASE1'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'NON_RANDOMIZED', 'maskingInfo': {'masking': 'NONE'}, 'primaryPurpose': 'TREATMENT', 'interventionModel': 'PARALLEL'}, 'enrollmentInfo': {'type': 'ACTUAL', 'count': 24}}, 'statusModule': {'overallStatus': 'TERMINATED', 'startDateStruct': {'date': '2007-11-14'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2018-08-01', 'completionDateStruct': {'date': '2016-10-03', 'type': 'ACTUAL'}, 'lastUpdateSubmitDate': '2018-08-02', 'studyFirstSubmitDate': '2011-09-30', 'studyFirstSubmitQcDate': '2011-09-30', 'lastUpdatePostDateStruct': {'date': '2018-08-03', 'type': 'ACTUAL'}, 'studyFirstPostDateStruct': {'date': '2011-10-03', 'type': 'ESTIMATED'}, 'primaryCompletionDateStruct': {'date': '2014-01-31', 'type': 'ACTUAL'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'Safety and MTD', 'timeFrame': '30 days after last dose', 'description': 'list of adverse events and highest dose at which fewer than 2 subjects experienced DLT'}, {'measure': 'Best overall response', 'timeFrame': 'Assessed every 42 days until disease progression', 'description': 'proportion of subjects experiencing complete response, partial response or stable disease as a best overall response'}]}, 'oversightModule': {'isFdaRegulatedDrug': True}, 'conditionsModule': {'keywords': ['Recombinant Immunotoxin', 'Monoclonal Antibody', 'Pseudomonas Exotoxin', 'Targeted Therapy', 'Pleural Mesothelioma', 'Mesothelioma', 'Epithelial Pleural Mesothelioma'], 'conditions': ['Mesothelioma']}, 'referencesModule': {'references': [{'pmid': '8552591', 'type': 'BACKGROUND', 'citation': 'Chang K, Pastan I. Molecular cloning of mesothelin, a differentiation antigen present on mesothelium, mesotheliomas, and ovarian cancers. Proc Natl Acad Sci U S A. 1996 Jan 9;93(1):136-40. doi: 10.1073/pnas.93.1.136.'}, {'pmid': '1244564', 'type': 'BACKGROUND', 'citation': 'Cockcroft DW, Gault MH. Prediction of creatinine clearance from serum creatinine. Nephron. 1976;16(1):31-41. doi: 10.1159/000180580.'}, {'pmid': '16082249', 'type': 'BACKGROUND', 'citation': 'Hassan R, Kreitman RJ, Pastan I, Willingham MC. Localization of mesothelin in epithelial ovarian cancer. Appl Immunohistochem Mol Morphol. 2005 Sep;13(3):243-7. doi: 10.1097/01.pai.00000141545.36485.d6.'}]}, 'descriptionModule': {'briefSummary': 'Background:\n\nStandard therapy for mesothelioma is a combination of the drugs pemetrexed and cisplatin. However, the benefits of this treatment are limited, and in most treated patients the disease continues to worsen.\n\nSS1(dsFV)PE38 is a genetically engineered drug. It contains an antibody that binds to a certain protein on mesothelioma cells and a toxin (type of poison) made from a product of a bacterium called Pseudomonas aeruginosa. It is hoped that the antibody will attach to the cancer cells, allowing the toxin to enter and kill the cells.\n\nObjectives:\n\nTo find out if SS1(dsFV)PE38, together with pemetrexed and cisplatin is safe and tolerable in patients with mesothelioma.\n\nTo determine the maximum tolerated dose of SS1(dsFV)PE38 (the highest dose that does not cause unacceptable side effects).\n\nTo see if SS1(dsFV)PE38 given with pemetrexed and cisplatin has any effect on patients tumors.\n\nTo learn how the body breaks down SS1(dsFV)PE38.\n\nEligibility:\n\nPatients 18 years of age and older with epithelial pleural mesothelioma whose disease cannot be cured with surgery, and have not had prior treatment with chemotherapy.\n\nDesign:\n\nTreatment with pemetrexed, cisplatin and SS1(dsFV)PE38 in two 21-day cycles as follows:\n\n* Day 1 - Intravenous (through a vein) infusions of pemetrexed and cisplatin.\n* Days 1 and 2 - Intravenous solution to prevent dehydration that might occur with SS1(dsFV)PE38.\n* Days 1, 3 and 5 Intravenous infusion of SS1(dsFV)PE38. Small groups (3 to 6) of patients are given SS1(dsFV)PE38 at a certain dose level. If the first group experiences no significant side effects, the next group a higher dose. This continues in succeeding groups until the maximum tolerated study dose (highest dose that patients can be given safely) is determined.\n\nContinuing standard treatment with additional cycles of pemetrexed and cisplatin.\n\nEvaluations during the treatment period:\n\n* Physical examination, including vital signs and body weight checks, and pregnancy test for women who can become pregnant.\n* Questions about medications and side effects.\n* Blood and urine tests.\n* Disease evaluation with CT, chest X-ray, and possibly PET scans, lung function tests, pulse oximetry, performance of daily activities and quality-of-life questionnaires.\n\nPost-treatment evaluations:\n\n* Clinic visits at months 1, 3, 6, 12, 15, 18 and 21 for physical examination and disease assessment.\n* End-of-study visit for blood tests, vital signs and weight measurements, disease assessment, electrocardiogram, pregnancy test for women who can become pregnant', 'detailedDescription': 'Background:\n\nSS1P (dsFv) PE38, is a recombinant immunotoxin targeting the tumor antigen mesothelin that is highly expressed in malignant mesothelioma. The maximum tolerated dose (MTD) of SS1 dsFv has been established in a phase I study.\n\nCombination therapy with pemetrexed plus cisplatin is the standard first line therapy for malignant mesothelioma, but results in a median overall survival of only 12.1 months.\n\nCombination of SS1(dsFv)PE38 with pemetrexed plus cisplatin could result in improved outcomes for patients with mesothelioma.\n\nObjectives:\n\nTo determine the MTD of SS1(dsFv)PE38 that can be safely administered in combination with pemetrexed plus cisplatin in patients with mesothelioma.\n\nTo characterize the toxicity profile of SS1(dsFv)PE38.\n\nTo study the pharmacokinetics of SS1(dsFv)PE388.\n\nTo observe anti-tumor activity, if any of SS1(dsFv)PE38 in combination with pemetrexed plus cisplatin.\n\nEligibility:\n\nSubjects with histologically confirmed epithelial pleural mesothelioma.\n\nNo prior radiotherapy (except palliative localized radiotherapy),systemic chemotherapy or biologic therapy for pleural mesothelioma.\n\nDesign:\n\nThis is a phase I dose-escalation study of SS1(dsFv)PE38 in combination with pemetrexed plus cisplatin.\n\nThe dose of pemetrexed plus cisplatin will be the standard dose approved for malignant mesothelioma. The dose of SS1(dsFv)PE38 will be escalated to find the safe dose in combination with pemetrexed plus cisplatin.\n\nSS1(dsFv)PE38 will be administered concurrently with pemetrexed plus cisplatin in cycles one and two, and subjects will receive additional cycles of pemetrexed and cisplatin as per standard practice.\n\nPatients will be assessed for response every 6 weeks.\n\nAn additional Single Cycle of SS1(dsFv)PE38 Cohort will involve up to 16 patients who will receive SS1(dsFv)PE38 administered for four or five doses during the first cycle concurrently with pemetrexed and cisplatin; subjects in this cohort will receive additional\n\ncycles of pemetrexed and cisplatin as per standard practice'}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['ADULT', 'OLDER_ADULT'], 'maximumAge': '100 Years', 'minimumAge': '18 Years', 'healthyVolunteers': False, 'eligibilityCriteria': '* INCLUSION CRITERIA:\n\nSubjects must meet all of the following criteria to be eligible to participate in the study:\n\nSubjects must have histologically confirmed epithelial or biphasic pleural mesothelioma not amenable to potentially curative surgical resection. However, patients with biphasic tumors that have a predominantly sarcomatoid component will be excluded.\n\nMeasurable disease\n\nSubjects must be greater than or equal to 18 years old\n\nKarnofsky Performance Status (KPS) of greater than or equal to 70\n\nLife expectancy of greater than 3 months, as assessed by the principal investigator.\n\nAdequate organ function with:Hepatic function: serum transaminases (either ALT or AST) or bilirubin, less than or equal to Grade 1, unless due to cancer or Gilbert s disease; less than or equal to Grade 2, if due to cancer\n\nRenal function: serum creatinine clearance greater than or equal to 60mL/min as estimated by Cockroft-Gault formula.\n\nBone marrow function: ANC of at least 1,500/mm (3), Platelet count at least 100,000/mm (3)\n\nPulmonary Function: FEV (1) greater than or equal to 50 percent of predicted value (post-pleural drainage and bronchodilation if these are indicated)\n\nMust be able to understand and sign informed consent\n\nFemale and male subjects agree to use an approved method of contraception during the study\n\nEXCLUSION CRITERIA:\n\nSubjects must not be pregnant or breast feeding\n\nPrior radiotherapy (except palliative extra-thoracic localized radiotherapy) or biologic therapy for malignant pleural mesothelioma within 4 weeks\n\nPrior systemic chemotherapy for malignant pleural mesothelioma\n\nDocumented and ongoing central nervous system involvement with their malignant disease (history of CNS involvement is not an exclusion criterion but the CNS metastases should have been adequately treated (radiation or surgical resection) and subjects are free from symptoms for 3 months off steroids).\n\nClinically significant heart disease (New York Heart Association Class III or IV)\n\nActive bacterial or fungal infection.\n\nBaseline coagulopathy greater than or equal to Grade 3 unless due to anticoagulant therapy\n\nSurgery or pleurodesis within 2 weeks\n\nHIV positive serology (due to increased risk of severe infection and unknown interaction of SS1(dsFv)PE38 with antiretroviral drugs)\n\nHepatitis B surface antigen positivity\n\nSubjects with other (non-mesothelioma) cancers who meet eligibility criteria and have had less than 5 years of disease-free survival will be considered on a case-by-case basis\n\nUncontrolled, symptomatic, intercurrent illness including but not limited to: infections requiring systemic antibiotics, unstable angina pectoris, cardiac arrhythmia, psychiatric illness, or social situations that would limit compliance with study requirements.'}, 'identificationModule': {'nctId': 'NCT01445392', 'briefTitle': 'SS1(dsFV)PE38 Plus Pemetrexed and Cisplatin to Treat Malignant Pleural Mesothelioma', 'nctIdAliases': ['NCT00575770'], 'organization': {'class': 'NIH', 'fullName': 'National Institutes of Health Clinical Center (CC)'}, 'officialTitle': 'A Phase 1, Single Center, Dose-Escalation Study of SS1(dsFv)PE38 Administered Concurrently With Pemetrexed and Cisplatin in Subjects With Unresectable Malignant Epithelial Pleural Mesothelioma', 'orgStudyIdInfo': {'id': '080026'}, 'secondaryIdInfos': [{'id': '08-C-0026'}]}, 'armsInterventionsModule': {'armGroups': [{'type': 'EXPERIMENTAL', 'label': '1', 'description': 'Multi-cycle cohort', 'interventionNames': ['Biological: Multicycle SS1P', 'Drug: Pemetrexed', 'Drug: Cisplatin']}, {'type': 'EXPERIMENTAL', 'label': '2', 'description': 'Single cycle cohort', 'interventionNames': ['Drug: Pemetrexed', 'Drug: Cisplatin', 'Biological: Single cycle SS1P']}], 'interventions': [{'name': 'Multicycle SS1P', 'type': 'BIOLOGICAL', 'description': 'Assigned dose level of SS1(dsFv)PE38 on days 1, 3 \\& 5 of a 21 day cycle for 2 cycles', 'armGroupLabels': ['1']}, {'name': 'Pemetrexed', 'type': 'DRUG', 'description': '500 mg/m\\^2 on day 1 of each 21 day cycle until disease progression', 'armGroupLabels': ['1', '2']}, {'name': 'Cisplatin', 'type': 'DRUG', 'description': '75 mg/m\\^2 on day 1 of each 21 day cycle until disease progression', 'armGroupLabels': ['1', '2']}, {'name': 'Single cycle SS1P', 'type': 'BIOLOGICAL', 'description': 'Patients 1 - 3 of single cycle cohort. 45 mcg/kg of SS1(dsFv)PE38 on 4 or 5 days (depending on dose level) of cycle 1 only.', 'armGroupLabels': ['2']}]}, 'contactsLocationsModule': {'locations': [{'zip': '20892', 'city': 'Bethesda', 'state': 'Maryland', 'country': 'United States', 'facility': 'National Institutes of Health Clinical Center, 9000 Rockville Pike', 'geoPoint': {'lat': 38.98067, 'lon': -77.10026}}], 'overallOfficials': [{'name': 'Raffit Hassan, M.D.', 'role': 'PRINCIPAL_INVESTIGATOR', 'affiliation': 'National Cancer Institute (NCI)'}]}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'National Cancer Institute (NCI)', 'class': 'NIH'}, 'responsibleParty': {'type': 'SPONSOR'}}}}