Ignite Creation Date:
2025-12-24 @ 11:08 PM
Ignite Modification Date:
2025-12-25 @ 8:40 PM
Study NCT ID:
NCT00278369
Status:
COMPLETED
Last Update Posted:
2013-05-22
First Post:
2006-01-16
Is NOT Gene Therapy:
False
Has Adverse Events:
False
Brief Title:
Pilot Study of Denileukin Diftitox Plus High-Dose IL-2 for Patients With Metastatic Renal Cancer
Sponsor:
Organization:
Raw JSON
{'hasResults': False, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'conditionBrowseModule': {'meshes': [{'id': 'D007680', 'term': 'Kidney Neoplasms'}, {'id': 'D002292', 'term': 'Carcinoma, Renal Cell'}], 'ancestors': [{'id': 'D014571', 'term': 'Urologic Neoplasms'}, {'id': 'D014565', 'term': 'Urogenital Neoplasms'}, {'id': 'D009371', 'term': 'Neoplasms by Site'}, {'id': 'D009369', 'term': 'Neoplasms'}, {'id': 'D052776', 'term': 'Female Urogenital Diseases'}, {'id': 'D005261', 'term': 'Female Urogenital Diseases and Pregnancy Complications'}, {'id': 'D000091642', 'term': 'Urogenital Diseases'}, {'id': 'D007674', 'term': 'Kidney Diseases'}, {'id': 'D014570', 'term': 'Urologic Diseases'}, {'id': 'D052801', 'term': 'Male Urogenital Diseases'}, {'id': 'D000230', 'term': 'Adenocarcinoma'}, {'id': 'D002277', 'term': 'Carcinoma'}, {'id': 'D009375', 'term': 'Neoplasms, Glandular and Epithelial'}, {'id': 'D009370', 'term': 'Neoplasms by Histologic Type'}]}, 'interventionBrowseModule': {'meshes': [{'id': 'C082598', 'term': 'aldesleukin'}, {'id': 'D007376', 'term': 'Interleukin-2'}, {'id': 'C078456', 'term': 'denileukin diftitox'}], 'ancestors': [{'id': 'D007378', 'term': 'Interleukins'}, {'id': 'D016207', 'term': 'Cytokines'}, {'id': 'D036341', 'term': 'Intercellular Signaling Peptides and Proteins'}, {'id': 'D010455', 'term': 'Peptides'}, {'id': 'D000602', 'term': 'Amino Acids, Peptides, and Proteins'}, {'id': 'D008222', 'term': 'Lymphokines'}, {'id': 'D011506', 'term': 'Proteins'}, {'id': 'D001685', 'term': 'Biological Factors'}]}}, 'protocolSection': {'designModule': {'phases': ['EARLY_PHASE1'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'RANDOMIZED', 'maskingInfo': {'masking': 'NONE'}, 'primaryPurpose': 'TREATMENT', 'interventionModel': 'PARALLEL'}, 'enrollmentInfo': {'type': 'ACTUAL', 'count': 20}}, 'statusModule': {'overallStatus': 'COMPLETED', 'startDateStruct': {'date': '2005-04'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2013-05', 'completionDateStruct': {'date': '2010-09', 'type': 'ACTUAL'}, 'lastUpdateSubmitDate': '2013-05-20', 'studyFirstSubmitDate': '2006-01-16', 'studyFirstSubmitQcDate': '2006-01-16', 'lastUpdatePostDateStruct': {'date': '2013-05-22', 'type': 'ESTIMATED'}, 'studyFirstPostDateStruct': {'date': '2006-01-18', 'type': 'ESTIMATED'}, 'primaryCompletionDateStruct': {'date': '2009-06', 'type': 'ACTUAL'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'The primary objective is to assess for toxicity', 'timeFrame': 'After each cycle of therapy and 30 days after the last treatment.', 'description': 'To assess the toxicity'}], 'secondaryOutcomes': [{'measure': 'The secondary objectives are to investigate differences in peak and duration of the expansion of CD4+, CD8+, CD4+CD 25+ and CD56+(dim and bright)CD25+ cells', 'timeFrame': 'Follow-up measurements must have met the SD criteria at least once after study entry at a minimum interval of 8 weeks.', 'description': 'To investigate differences in peak and duration.'}, {'measure': 'To investigate the effects of denileukin diftitox in combination with IL-2 on plasma TGF-beta levels', 'timeFrame': 'Cohort 1: Denileukin diftitox dose of 6μg/kg/ Days 1, 2, 3, 4, and 5. Cohort 2 Denileukin diftitox dose of 9μg/kg given 4, 3, 2, and 1 days prior to 1st day of each cycle. Cohort 3: Denileukin diftitox dose of 9μg/kg given days 8 and 9.', 'description': 'To investigate the effects of denileukin diftitox'}, {'measure': 'To perform TGF-beta promoter and TGF-beta receptor genotyping prior to the start of treatment to search for variants that may be associated with tumor response to therapy.', 'timeFrame': 'Cohort 1: Plasma TGF-beta levels to be given on day. Cohort 2: plasma TGF-beta levels to be given at day 1. Cohort 3: plasma TGF-beta levels given on days 1 through 5.', 'description': 'To perform TGF-beta promoter and TGF-beta receptor genotyping'}, {'measure': 'Overall response rate and time to progression', 'timeFrame': 'CT scans and other pertinent studies will be performed at week 10 to assess response.', 'description': 'Overall response rate will be assessed.'}]}, 'oversightModule': {'oversightHasDmc': True}, 'conditionsModule': {'keywords': ['recurrent renal cell cancer', 'stage IV renal cell cancer', 'clear cell renal cell carcinoma'], 'conditions': ['Kidney Cancer']}, 'descriptionModule': {'briefSummary': 'RATIONALE: Combinations of biological substances in denileukin diftitox may be able to carry tumor-killing substances directly to kidney cancer cells. Interleukin-2 may stimulate the white blood cells to kill kidney cancer cells. Giving denileukin diftitox together with interleukin-2 may kill more tumor cells.\n\nPURPOSE: This randomized phase I trial is studying the side effects of denileukin diftitox and interleukin-2 in treating patients with metastatic kidney cancer.', 'detailedDescription': 'OBJECTIVES:\n\nPrimary\n\n* Determine the toxic effects of denileukin diftitox and high-dose interleukin-2 in patients with metastatic renal cell cancer.\n\nSecondary\n\n* Perform transforming growth factor (TGF)-beta promoter and TGF-beta receptor genotyping to search for variants that may be associated with tumor response to therapy.\n* Determine the overall response rate (partial and complete) in patients treated with this regimen.\n* Determine the time to progression in patients treated with this regimen.\n\nOUTLINE: This is a randomized, pilot study.\n\nThe first 3 patients enrolled in the study receive high-dose interleukin-2 (IL-2) IV over 15 minutes, 3 times daily, on days 1-5 and 15-19 and denileukin diftitox IV over 15-60 minutes once daily on days 8-10. If no dose-limiting toxicity occurs after receiving denileukin diftitox, subsequent patients are randomized to 1 of 2 treatment arms.\n\n* Arm I: Patients receive denileukin diftitox (at a higher dose than for the first 3 patients enrolled in the study) IV over 15-60 minutes once daily on days -4 to -2 and high-dose IL-2 IV over 15 minutes, 3 times daily, on days 1-5 and 15-19.\n* Arm II: Patients receive high-dose IL-2 as in arm I and denileukin diftitox (at a higher dose than for the first 3 patients enrolled in the study) IV over 15-60 minutes at a higher dose once daily on days 8-10.\n\nAll patients may receive additional treatment with IL-2 alone in the absence of disease progression or unacceptable toxicity.\n\nAfter completion of study treatment, patients are followed periodically for at least 4 years.\n\nPROJECTED ACCRUAL: A total of 13 patients will be accrued for this study.'}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['ADULT', 'OLDER_ADULT'], 'minimumAge': '18 Years', 'healthyVolunteers': False, 'eligibilityCriteria': 'DISEASE CHARACTERISTICS:\n\n* Documented histologically confirmed metastatic renal cell carcinoma\n\n * Clear cell histology\n* Disease must be measurable as defined by lesions that can be accurately measured in at least one dimension with longest diameter \\> 20 mm using conventional techniques or \\> 10 mm with spiral CT scan\n\n * Must have at least one measurable lesion\n * If the measurable disease is restricted to a solitary lesion, its neoplastic nature should be confirmed by cytology/histology\n * Clinical lesions will only be considered measurable when they are superficial (e.g., skin nodules and palpable lymph nodes)\n * The following are considered nonmeasurable lesions:\n\n * Bone lesions\n * Leptomeningeal disease\n * Ascites\n * Pleural/pericardial effusion\n * Inflammatory breast disease\n * Lymphangitis cutis/pulmonis\n * Cystic lesions\n * Abdominal masses not confirmed and followed by imaging techniques\n* No CNS metastases\n\nPATIENT CHARACTERISTICS:\n\n* ECOG performance status \\< 2\n* Life expectancy of at least 4 months\n* Serum creatinine \\< 2.0 mg/dL OR creatinine clearance \\> 50 mL/min\n* Total bilirubin normal\n* Platelets \\> 100,000/mm³\n* WBC \\> 3,500/mm³\n* No evidence of congestive heart failure\n* No symptoms of coronary artery disease\n* No serious cardiac arrhythmias\n* A pretreatment cardiac stress test must be performed within 42 days of IL-2 treatment if any cardiac symptoms are present (patients with documented ischemia on the pretreatment cardiac stress test will be excluded from the study)\n* Adequate pulmonary reserve\n\n * Pulmonary function tests (PFTs) must be performed within 42 days of IL-2 treatment\n\n * FEV\\_1 \\> 2.0 liters of \\> 75% predicted for height and age\n * Patients unable to perform PFTs will be excluded\n* Women who are pregnant or lactating are not eligible\n* Women of childbearing potential and sexually active males must commit to the use of effective contraception while on study\n* Negative pregnancy test\n* No known HIV-positive patients\n* No evidence of active infection requiring antibiotic therapy\n* Must not have a contraindication to treatment with pressor agents\n* Must not have any significant medical disease that, in the opinion of the investigator, may interfere with completion of the study\n* No history of another malignancy within the past 5 years other than basal cell skin cancer\n\nPRIOR CONCURRENT THERAPY:\n\n* Recovered from all toxic effects of prior therapy\n* Must not currently receive chronic medication for asthma\n* No prior interleukin-2 (IL-2) therapy\n* No prior organ allografts\n* No systemic corticosteroids in the 4 weeks prior to treatment\n* No concurrent systemic steroids\n* No radiotherapy, chemotherapy, or immunotherapy in the 4 weeks prior to the first dose of study treatment\n* No concurrent radiotherapy, chemotherapy, or other immunotherapy\n* No previous investigational agent within 4 weeks prior to the start of study treatment'}, 'identificationModule': {'nctId': 'NCT00278369', 'briefTitle': 'Pilot Study of Denileukin Diftitox Plus High-Dose IL-2 for Patients With Metastatic Renal Cancer', 'organization': {'class': 'OTHER', 'fullName': 'Northwestern University'}, 'officialTitle': 'A Pilot Study of Denileukin Diftitox in Combination With High-Dose IL-2 for Patients With Metastatic Renal Cell Carcinoma', 'orgStudyIdInfo': {'id': 'NU 04U1'}, 'secondaryIdInfos': [{'id': 'P30CA060553', 'link': 'https://reporter.nih.gov/quickSearch/P30CA060553', 'type': 'NIH'}, {'id': 'NU-04U1'}, {'id': 'STU00006770', 'type': 'OTHER', 'domain': 'Northwestern University IRB'}]}, 'armsInterventionsModule': {'armGroups': [{'type': 'EXPERIMENTAL', 'label': 'A', 'description': '6 mcg/kg Denileukin Diftitox administered IV/daily on days 8-10 of standard interleukin 2 dose course', 'interventionNames': ['Biological: aldesleukin', 'Biological: denileukin diftitox']}, {'type': 'EXPERIMENTAL', 'label': 'B', 'description': '9 mcg/kg Denileukin Diftitox administered IV/daily on days -4 to -2 of standard interleukin 2 dose course', 'interventionNames': ['Biological: aldesleukin', 'Biological: denileukin diftitox']}, {'type': 'EXPERIMENTAL', 'label': 'C', 'description': '9 mcg/kg Denileukin Diftitox administered IV/daily on days 8-10 of standard interleukin 2 dose course', 'interventionNames': ['Biological: aldesleukin', 'Biological: denileukin diftitox']}], 'interventions': [{'name': 'aldesleukin', 'type': 'BIOLOGICAL', 'otherNames': ['IL-2', 'Interleukin-2', 'Proleukin'], 'description': 'The IL-2 is given as a 15-minute infusion through an intravenous catheter (I.V.), a small plastic tube that is put into your vein for the time you are receiving the study treatment. IL-2 is given through the I.V. once every 8 hours for 5 days (days 1-5). A second 5 day cycle of IL-2 will begin on the 15th day (days 15-19). This is one complete cycle (days 1-19) of IL-2 treatment', 'armGroupLabels': ['A', 'B', 'C']}, {'name': 'denileukin diftitox', 'type': 'BIOLOGICAL', 'otherNames': ['ONTAK (denileukin diftitox)', 'DAB 389 IL-2'], 'description': 'Denileukin diftitox will be administered once daily as a 15 to 60 minute infusion for 3 consecutive days.', 'armGroupLabels': ['A', 'B', 'C']}]}, 'contactsLocationsModule': {'locations': [{'zip': '60611-3013', 'city': 'Chicago', 'state': 'Illinois', 'country': 'United States', 'facility': 'Robert H. Lurie Comprehensive Cancer Center at Northwestern University', 'geoPoint': {'lat': 41.85003, 'lon': -87.65005}}], 'overallOfficials': [{'name': 'Timothy M. Kuzel, MD', 'role': 'STUDY_CHAIR', 'affiliation': 'Robert H. Lurie Cancer Center'}]}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'Northwestern University', 'class': 'OTHER'}, 'collaborators': [{'name': 'National Cancer Institute (NCI)', 'class': 'NIH'}], 'responsibleParty': {'type': 'PRINCIPAL_INVESTIGATOR', 'investigatorTitle': 'Timothy Kuzel, MD', 'investigatorFullName': 'Timothy Kuzel', 'investigatorAffiliation': 'Northwestern University'}}}}