Ignite Creation Date:
2025-12-25 @ 2:00 AM
Ignite Modification Date:
2025-12-27 @ 6:06 AM
Study NCT ID:
NCT04887194
Status:
COMPLETED
Last Update Posted:
2024-05-08
First Post:
2021-05-04
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
PK Study to Assess Drug-drug Interaction and QTc Between Sitravatinib and a Cocktail of Substrates
Sponsor:
Organization:
Raw JSON
{'hasResults': False, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'interventionBrowseModule': {'meshes': [{'id': 'C000611865', 'term': 'sitravatinib'}, {'id': 'D014859', 'term': 'Warfarin'}, {'id': 'D003915', 'term': 'Dextromethorphan'}, {'id': 'D000111', 'term': 'Acetylcysteine'}, {'id': 'D008874', 'term': 'Midazolam'}, {'id': 'D004077', 'term': 'Digoxin'}, {'id': 'D000068718', 'term': 'Rosuvastatin Calcium'}, {'id': 'D000077594', 'term': 'Nivolumab'}], 'ancestors': [{'id': 'D015110', 'term': '4-Hydroxycoumarins'}, {'id': 'D003374', 'term': 'Coumarins'}, {'id': 'D001578', 'term': 'Benzopyrans'}, {'id': 'D011714', 'term': 'Pyrans'}, {'id': 'D006573', 'term': 'Heterocyclic Compounds, 1-Ring'}, {'id': 'D006571', 'term': 'Heterocyclic Compounds'}, {'id': 'D006574', 'term': 'Heterocyclic Compounds, 2-Ring'}, {'id': 'D000072471', 'term': 'Heterocyclic Compounds, Fused-Ring'}, {'id': 'D009019', 'term': 'Morphinans'}, {'id': 'D053610', 'term': 'Opiate Alkaloids'}, {'id': 'D000470', 'term': 'Alkaloids'}, {'id': 'D006572', 'term': 'Heterocyclic Compounds, Bridged-Ring'}, {'id': 'D006576', 'term': 'Heterocyclic Compounds, 4 or More Rings'}, {'id': 'D010616', 'term': 'Phenanthrenes'}, {'id': 'D011084', 'term': 'Polycyclic Aromatic Hydrocarbons'}, {'id': 'D011083', 'term': 'Polycyclic Compounds'}, {'id': 'D003545', 'term': 'Cysteine'}, {'id': 'D000603', 'term': 'Amino Acids, Sulfur'}, {'id': 'D013457', 'term': 'Sulfur Compounds'}, {'id': 'D009930', 'term': 'Organic Chemicals'}, {'id': 'D000596', 'term': 'Amino Acids'}, {'id': 'D000602', 'term': 'Amino Acids, Peptides, and Proteins'}, {'id': 'D001569', 'term': 'Benzodiazepines'}, {'id': 'D001552', 'term': 'Benzazepines'}, {'id': 'D004071', 'term': 'Digitalis Glycosides'}, {'id': 'D002298', 'term': 'Cardenolides'}, {'id': 'D002301', 'term': 'Cardiac Glycosides'}, {'id': 'D002297', 'term': 'Cardanolides'}, {'id': 'D013256', 'term': 'Steroids'}, {'id': 'D000072473', 'term': 'Fused-Ring Compounds'}, {'id': 'D006027', 'term': 'Glycosides'}, {'id': 'D002241', 'term': 'Carbohydrates'}, {'id': 'D013449', 'term': 'Sulfonamides'}, {'id': 'D000577', 'term': 'Amides'}, {'id': 'D005464', 'term': 'Fluorobenzenes'}, {'id': 'D006845', 'term': 'Hydrocarbons, Fluorinated'}, {'id': 'D006846', 'term': 'Hydrocarbons, Halogenated'}, {'id': 'D006838', 'term': 'Hydrocarbons'}, {'id': 'D013450', 'term': 'Sulfones'}, {'id': 'D011743', 'term': 'Pyrimidines'}, {'id': 'D061067', 'term': 'Antibodies, Monoclonal, Humanized'}, {'id': 'D000911', 'term': 'Antibodies, Monoclonal'}, {'id': 'D000906', 'term': 'Antibodies'}, {'id': 'D007136', 'term': 'Immunoglobulins'}, {'id': 'D007162', 'term': 'Immunoproteins'}, {'id': 'D001798', 'term': 'Blood Proteins'}, {'id': 'D011506', 'term': 'Proteins'}, {'id': 'D012712', 'term': 'Serum Globulins'}, {'id': 'D005916', 'term': 'Globulins'}]}}, 'protocolSection': {'designModule': {'phases': ['PHASE1'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'NON_RANDOMIZED', 'maskingInfo': {'masking': 'NONE'}, 'primaryPurpose': 'TREATMENT', 'interventionModel': 'SEQUENTIAL', 'interventionModelDescription': 'Two Part, Phase 1 study enrolling patients with advanced tumor types into two cohorts: drug-drug interaction (DDI) and QTc. All patients receive the same anticancer treatment.'}, 'enrollmentInfo': {'type': 'ACTUAL', 'count': 40}}, 'statusModule': {'overallStatus': 'COMPLETED', 'startDateStruct': {'date': '2021-04-08', 'type': 'ACTUAL'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2024-05', 'completionDateStruct': {'date': '2022-12-22', 'type': 'ACTUAL'}, 'lastUpdateSubmitDate': '2024-05-07', 'studyFirstSubmitDate': '2021-05-04', 'studyFirstSubmitQcDate': '2021-05-06', 'lastUpdatePostDateStruct': {'date': '2024-05-08', 'type': 'ACTUAL'}, 'studyFirstPostDateStruct': {'date': '2021-05-14', 'type': 'ACTUAL'}, 'primaryCompletionDateStruct': {'date': '2022-12-22', 'type': 'ACTUAL'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'PK parameters of probe drugs; AUC from time zero to the last data point (AUC-last)', 'timeFrame': 'Part 1; 1-20 Days', 'description': '(warfarin, dextromethorphan, midazolam, digoxin, and rosuvastatin) derived from the plasma concentration time profile before and after oral administration of sitravatinib'}, {'measure': 'PK parameters of probe drugs; AUC from time zero to infinity (AUC∞)', 'timeFrame': 'Part 1; 1-20 Days', 'description': '(warfarin, dextromethorphan, midazolam, digoxin, and rosuvastatin) derived from the plasma concentration time profile before and after oral administration of sitravatinib'}, {'measure': 'PK parameters of probe drugs; C-max', 'timeFrame': 'Part 1; 1-20 Days', 'description': '(warfarin, dextromethorphan, midazolam, digoxin, and rosuvastatin) derived from the plasma concentration time profile before and after oral administration of sitravatinib'}, {'measure': 'Adverse Events', 'timeFrame': 'Through study completion, an average of 12 months', 'description': 'Characterization of AEs by incidence, severity, timing, seriousness \\& relationship to study treatment'}], 'secondaryOutcomes': [{'measure': 'Plasma PK parameters of sitravatinib and M10; C-max', 'timeFrame': '1-20 Days', 'description': 'C-max'}, {'measure': 'Plasma PK parameters of sitravatinib and M10; AUC over the dosing interval (AUC)', 'timeFrame': '1-20 Days', 'description': 'AUC over the dosing interval (AUC)'}, {'measure': 'Plasma PK parameters of sitravatinib and M10; trough plasma concentration (C-trough)', 'timeFrame': '1-20 Days', 'description': 'trough plasma concentration (C-trough)'}, {'measure': 'Plasma PK parameters of sitravatinib and M10; time to maximum concentration (t-max)', 'timeFrame': '1-20 Days', 'description': 'time to maximum concentration (t-max)'}, {'measure': 'Adverse Events', 'timeFrame': '1-20 Days', 'description': 'Safety characterized by type, incidence, severity, timing, seriousness \\& relationship to study treatment of adverse events, and laboratory abnormalities'}, {'measure': 'QT/QTc', 'timeFrame': 'Part 1: Pre-dose to Day 10 (QTc cohort); Part 1: Pre-dose to Day14 (DDI cohort)', 'description': 'ECG data'}]}, 'oversightModule': {'oversightHasDmc': False, 'isFdaRegulatedDrug': True, 'isFdaRegulatedDevice': False}, 'conditionsModule': {'conditions': ['Advanced Solid Tumor']}, 'descriptionModule': {'briefSummary': 'Study 516-010 is an open-label Phase 1, drug-drug interaction and QTc study evaluating the effect of sitravatinib on probe substrates for CYP450 enzymes and BCRP and P-gp transporters.', 'detailedDescription': 'Part 1 of this study is designed to evaluate the potential for drug-drug interactions and QTc effects with sitravatinib monotherapy when administered with probe drugs for specific cytochrome P450 (CYP) enzymes (CYP2C9, CYP2D6, and CYP3A4) and P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP) transporters\n\nPart 2 allows for patients to continue sitravatinib treatment with the addition of the checkpoint inhibitor Nivolumab.'}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['ADULT', 'OLDER_ADULT'], 'minimumAge': '18 Years', 'healthyVolunteers': False, 'eligibilityCriteria': 'Inclusion Criteria:\n\n* Confirmed diagnosis of unresectable advanced/metastatic solid tumor\n* Life expectancy of at least 3 months\n* Adequate bone marrow and organ function\n\nExclusion Criteria:\n\n* Ongoing medical condition or need for treatment with medication that may affect the PK of study treatments during Part 1\n* Immunocompromising conditions\n* Impaired heart function\n* Active or prior documented autoimmune disease'}, 'identificationModule': {'nctId': 'NCT04887194', 'briefTitle': 'PK Study to Assess Drug-drug Interaction and QTc Between Sitravatinib and a Cocktail of Substrates', 'organization': {'class': 'INDUSTRY', 'fullName': 'Mirati Therapeutics Inc.'}, 'officialTitle': 'A Two-cohort, Two-part, Phase 1, Multicenter, Open-label, Fixed-sequence, Drug-Drug Interaction and QTc Assessments of Sitravatinib Followed by Combination Treatment With Nivolumab in Patients With Advanced Solid Malignancies', 'orgStudyIdInfo': {'id': '516-010'}}, 'armsInterventionsModule': {'armGroups': [{'type': 'EXPERIMENTAL', 'label': 'Phase 1, Part 1: Sitravatinib monotherapy (DDI cohort)', 'description': 'To evaluate the potential for drug-drug interactions (DDI) with sitravatinib monotherapy. To determine the effect of sitravatinib on the pharmacokinetics (PK) of midazolam (CYP3A4 probe substrate), warfarin (CYP2C9 probe substrate), dextromethorphan (CYP2D6 probe substrate), rosuvastatin (BCRP probe substrate), and digoxin (P-gp probe substrate).', 'interventionNames': ['Drug: Sitravatinib', 'Drug: Warfarin', 'Drug: Dextromethorphan', 'Drug: Midazolam', 'Drug: Digoxin', 'Drug: Rosuvastatin']}, {'type': 'EXPERIMENTAL', 'label': 'Phase 1, Part 1: Sitravatinib monotherapy (QTc cohort)', 'description': 'To evaluate the QTc prolongation risk for sitravatinib in patients with advanced/metastatic solid tumors via C-QTc modeling.', 'interventionNames': ['Drug: Sitravatinib']}, {'type': 'EXPERIMENTAL', 'label': 'Phase 1, Part 2: Combination Therapy (both DDI and QTc cohorts)', 'description': 'To evaluate safety and tolerability of Sitravatinib treatment with the addition of the checkpoint inhibitor nivolumab.', 'interventionNames': ['Drug: Sitravatinib', 'Drug: Nivolumab']}], 'interventions': [{'name': 'Sitravatinib', 'type': 'DRUG', 'otherNames': ['MGCD516'], 'description': 'Sitravatinib is a small molecule inhibitor of receptor tyrosine kinases', 'armGroupLabels': ['Phase 1, Part 1: Sitravatinib monotherapy (DDI cohort)', 'Phase 1, Part 1: Sitravatinib monotherapy (QTc cohort)', 'Phase 1, Part 2: Combination Therapy (both DDI and QTc cohorts)']}, {'name': 'Warfarin', 'type': 'DRUG', 'otherNames': ['Coumadin'], 'description': 'CYP2C9 probe substrate', 'armGroupLabels': ['Phase 1, Part 1: Sitravatinib monotherapy (DDI cohort)']}, {'name': 'Dextromethorphan', 'type': 'DRUG', 'otherNames': ['Robitussin'], 'description': 'CYP2D6 probe substrate', 'armGroupLabels': ['Phase 1, Part 1: Sitravatinib monotherapy (DDI cohort)']}, {'name': 'Midazolam', 'type': 'DRUG', 'otherNames': ['Versed'], 'description': 'CYP3A4 probe substrate', 'armGroupLabels': ['Phase 1, Part 1: Sitravatinib monotherapy (DDI cohort)']}, {'name': 'Digoxin', 'type': 'DRUG', 'otherNames': ['LANOXICAPS'], 'description': 'P-gp probe substrate', 'armGroupLabels': ['Phase 1, Part 1: Sitravatinib monotherapy (DDI cohort)']}, {'name': 'Rosuvastatin', 'type': 'DRUG', 'otherNames': ['Crestor'], 'description': 'BCRP probe substrate', 'armGroupLabels': ['Phase 1, Part 1: Sitravatinib monotherapy (DDI cohort)']}, {'name': 'Nivolumab', 'type': 'DRUG', 'otherNames': ['OPDIVO'], 'description': 'Nivolumab is a programmed death receptor (PD-1) blocking antibody', 'armGroupLabels': ['Phase 1, Part 2: Combination Therapy (both DDI and QTc cohorts)']}]}, 'contactsLocationsModule': {'locations': [{'zip': '46526', 'city': 'Goshen', 'state': 'Indiana', 'country': 'United States', 'facility': 'Goshen Health', 'geoPoint': {'lat': 41.58227, 'lon': -85.83444}}, {'zip': '78758', 'city': 'Austin', 'state': 'Texas', 'country': 'United States', 'facility': 'NEXT Oncology', 'geoPoint': {'lat': 30.26715, 'lon': -97.74306}}, {'zip': '78229', 'city': 'San Antonio', 'state': 'Texas', 'country': 'United States', 'facility': 'NEXT Oncology', 'geoPoint': {'lat': 29.42412, 'lon': -98.49363}}, {'zip': '22031', 'city': 'Fairfax', 'state': 'Virginia', 'country': 'United States', 'facility': 'NEXT Oncology', 'geoPoint': {'lat': 38.84622, 'lon': -77.30637}}, {'zip': '98402', 'city': 'Tacoma', 'state': 'Washington', 'country': 'United States', 'facility': 'MultiCare Health System', 'geoPoint': {'lat': 47.25288, 'lon': -122.44429}}], 'overallOfficials': [{'name': 'Curtis Chin, MD', 'role': 'STUDY_DIRECTOR', 'affiliation': 'Mirati Therapeutics Inc.'}]}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'Mirati Therapeutics Inc.', 'class': 'INDUSTRY'}, 'responsibleParty': {'type': 'SPONSOR'}}}}