Ignite Creation Date:
2025-12-25 @ 4:49 AM
Ignite Modification Date:
2025-12-26 @ 3:51 AM
Study NCT ID:
NCT05683418
Status:
RECRUITING
Last Update Posted:
2025-07-22
First Post:
2022-11-12
Is NOT Gene Therapy:
False
Has Adverse Events:
False
Brief Title:
A Study to Evaluate the Safety and Tolerability of TOS-358 in Adults With HR+ Breast Cancer and Other Select Solid Tumors
Sponsor:
Organization:
Raw JSON
{'hasResults': False, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'conditionBrowseModule': {'meshes': [{'id': 'D000077195', 'term': 'Squamous Cell Carcinoma of Head and Neck'}, {'id': 'D016889', 'term': 'Endometrial Neoplasms'}, {'id': 'D001749', 'term': 'Urinary Bladder Neoplasms'}, {'id': 'D009477', 'term': 'Hereditary Sensory and Autonomic Neuropathies'}], 'ancestors': [{'id': 'D002294', 'term': 'Carcinoma, Squamous Cell'}, {'id': 'D002277', 'term': 'Carcinoma'}, {'id': 'D009375', 'term': 'Neoplasms, Glandular and Epithelial'}, {'id': 'D009370', 'term': 'Neoplasms by Histologic Type'}, {'id': 'D009369', 'term': 'Neoplasms'}, {'id': 'D006258', 'term': 'Head and Neck Neoplasms'}, {'id': 'D009371', 'term': 'Neoplasms by Site'}, {'id': 'D014594', 'term': 'Uterine Neoplasms'}, {'id': 'D005833', 'term': 'Genital Neoplasms, Female'}, {'id': 'D014565', 'term': 'Urogenital Neoplasms'}, {'id': 'D014591', 'term': 'Uterine Diseases'}, {'id': 'D005831', 'term': 'Genital Diseases, Female'}, {'id': 'D052776', 'term': 'Female Urogenital Diseases'}, {'id': 'D005261', 'term': 'Female Urogenital Diseases and Pregnancy Complications'}, {'id': 'D000091642', 'term': 'Urogenital Diseases'}, {'id': 'D000091662', 'term': 'Genital Diseases'}, {'id': 'D014571', 'term': 'Urologic Neoplasms'}, {'id': 'D001745', 'term': 'Urinary Bladder Diseases'}, {'id': 'D014570', 'term': 'Urologic Diseases'}, {'id': 'D052801', 'term': 'Male Urogenital Diseases'}, {'id': 'D009421', 'term': 'Nervous System Malformations'}, {'id': 'D009422', 'term': 'Nervous System Diseases'}, {'id': 'D020271', 'term': 'Heredodegenerative Disorders, Nervous System'}, {'id': 'D019636', 'term': 'Neurodegenerative Diseases'}, {'id': 'D011115', 'term': 'Polyneuropathies'}, {'id': 'D010523', 'term': 'Peripheral Nervous System Diseases'}, {'id': 'D009468', 'term': 'Neuromuscular Diseases'}, {'id': 'D000013', 'term': 'Congenital Abnormalities'}, {'id': 'D009358', 'term': 'Congenital, Hereditary, and Neonatal Diseases and Abnormalities'}, {'id': 'D030342', 'term': 'Genetic Diseases, Inborn'}]}}, 'protocolSection': {'designModule': {'phases': ['PHASE1'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'NA', 'maskingInfo': {'masking': 'NONE'}, 'primaryPurpose': 'TREATMENT', 'interventionModel': 'SINGLE_GROUP', 'interventionModelDescription': 'TOS-358 Single Agent Arm:\n\nPart 1 (multiple ascending doses, QD or BID): locally advanced, recurrent or metastatic HR+ breast, endometrial, urothelial or squamous cell carcinoma of the head and neck, with PIK3CA mutation per local assessment; Part 2 (RP2D determined in Part 1) Patients with locally advanced, recurrent or metastatic HR+ breast cancer with PIK3CA mutation per local assessment will be enrolled protocol defined groups.'}, 'enrollmentInfo': {'type': 'ESTIMATED', 'count': 241}}, 'statusModule': {'overallStatus': 'RECRUITING', 'startDateStruct': {'date': '2023-02-15', 'type': 'ACTUAL'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2025-07', 'completionDateStruct': {'date': '2026-12', 'type': 'ESTIMATED'}, 'lastUpdateSubmitDate': '2025-07-17', 'studyFirstSubmitDate': '2022-11-12', 'studyFirstSubmitQcDate': '2023-01-05', 'lastUpdatePostDateStruct': {'date': '2025-07-22', 'type': 'ACTUAL'}, 'studyFirstPostDateStruct': {'date': '2023-01-13', 'type': 'ACTUAL'}, 'primaryCompletionDateStruct': {'date': '2026-12', 'type': 'ESTIMATED'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'Determine the rate of dose-limiting toxicities (DLTs)', 'timeFrame': 'First 21 days of treatment'}, {'measure': 'Incidence and severity of adverse events (AEs) and specific laboratory abnormalities graded according to NCI CTCAE v5', 'timeFrame': 'Start of treatment to 30 days after last dose'}]}, 'oversightModule': {'oversightHasDmc': False, 'isFdaRegulatedDrug': True, 'isFdaRegulatedDevice': False}, 'conditionsModule': {'keywords': ['PI3K-alpha'], 'conditions': ['Squamous Cell Carcinoma of Head and Neck', 'Endometrial Cancer', 'HR+/HER2-negative Breast Cancer', 'Bladder Cancer']}, 'descriptionModule': {'briefSummary': 'The goal of this clinical trial is to evaluate the safety of TOS-358 in adults with select solid tumors who meet study enrollment criteria. The main questions it aims to answer are:\n\n1. what is the maximum tolerated dose and recommended dose for phase 2?\n2. how safe and tolerable is TOS-358 at different dose levels when taken orally once or twice per day?', 'detailedDescription': 'This study will be conducted in two parts: a dose finding portion to determine the maximum tolerated dose and recommended phase 2 dose (RP2D) of TOS-358 administered orally on once a day (QD) and twice daily (BID) schedules, and a dose expansion portion to evaluate safety and tolerability in tumor-specific cohorts administered TOS-358 at the recommended phase 2 dose and schedule.\n\nAdult subjects with histologically confirmed diagnosis of hormone receptor-positive (HR+), human epidermal growth factor receptor 2 (HER2) negative breast cancer, squamous cell carcinoma of the head and neck, cancer of the bladder, or endometrial cancer with known PIK3CA mutations or amplifications and who meet all of the eligibility criteria will be enrolled in the study.\n\nIn the dose finding portion of the study, TOS-358 will be evaluated as a single-agent at multiple dose levels administered orally until disease progression, unacceptable toxicity, or until meeting any other reason for discontinuation as specified in the protocol.'}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['ADULT', 'OLDER_ADULT'], 'minimumAge': '18 Years', 'healthyVolunteers': False, 'eligibilityCriteria': 'Key Inclusion Criteria\n\n* Locally advanced, recurrent, or metastatic, incurable (any number of previous lines of therapy is allowed), histologically or cytologically confirmed; HR +/HER2- breast cancer; squamous cell carcinoma of the head and neck; urothelial cancer; or endometrial cancer with no more than 3 prior lines of therapy for metastatic disease\n* Willing and able to provide written informed consent for this study\n* Adults ≥ 18 years old at time of consent\n* Known PIK3CA mutations or amplifications as determined at a CAP/CLIA-certified or equivalently accredited diagnostic laboratory using a validated test\n* Measurable disease by RECIST 1.1\n* Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1\n* Life expectancy ≥ 6 months, as determined by the investigator\n* Adequate bone marrow, liver, and kidney function within 14 days prior to first dose of investigational product\n* Fasting plasma glucose \\<= 140 mg/dL AND hemoglobin A1c (HbA1c) \\<= 7.0%\n* Available archived or fresh tumor tissue sample for detection of PIK3CA mutation by central laboratory test\n\nKey Exclusion Criteria\n\n* Recent systemic anticancer treatment prior to start of treatment (EXCEPTION: Patients with breast cancer who were receiving a fulvestrant-containing regimen at the time of informed consent may remain on fulvestrant while receiving study treatment)\n* For non-breast cancer: prior treatment with any PI3K, AKT, or mTOR inhibitor, or any agent whose mechanism of action is to inhibit the PI3K-AKT-mTOR pathway,\n* Has an established diagnosis of diabetes mellitus type 1 or has uncontrolled diabetes mellitus type 2 requiring antihyperglycemic medication\n* Known active central nervous system (CNS) metastases.'}, 'identificationModule': {'nctId': 'NCT05683418', 'briefTitle': 'A Study to Evaluate the Safety and Tolerability of TOS-358 in Adults With HR+ Breast Cancer and Other Select Solid Tumors', 'organization': {'class': 'INDUSTRY', 'fullName': 'Totus Medicines'}, 'officialTitle': 'A Study to Evaluate the Safety and Tolerability of the Covalent Phosphoinositide-3-Kinase (PI3K)-Alpha Inhibitor, TOS-358, in Adult Subjects With Select Solid Tumors', 'orgStudyIdInfo': {'id': 'TOS-358-001'}, 'secondaryIdInfos': [{'id': '2023-505346-26-01', 'type': 'CTIS'}]}, 'armsInterventionsModule': {'armGroups': [{'type': 'EXPERIMENTAL', 'label': 'TOS-358 Single Agent Arm', 'description': 'Multiple doses of TOS-358 for oral administration.', 'interventionNames': ['Drug: TOS-358']}], 'interventions': [{'name': 'TOS-358', 'type': 'DRUG', 'description': 'Covalent Phosphoinositide-3-Kinase (PI3K)-alpha Inhibitor', 'armGroupLabels': ['TOS-358 Single Agent Arm']}]}, 'contactsLocationsModule': {'locations': [{'zip': '90033', 'city': 'Los Angeles', 'state': 'California', 'status': 'RECRUITING', 'country': 'United States', 'contacts': [{'name': 'Xiomara Menendez, RN', 'role': 'CONTACT', 'email': 'Xiomara.Menendez@med.usc.edu'}, {'name': 'Anthony El-Khoueiry, MD', 'role': 'PRINCIPAL_INVESTIGATOR'}], 'facility': 'University of Southern California, Norris Comprehensive Cancer Center', 'geoPoint': {'lat': 34.05223, 'lon': -118.24368}}, {'zip': '60611', 'city': 'Chicago', 'state': 'Illinois', 'status': 'RECRUITING', 'country': 'United States', 'contacts': [{'name': 'Study Coordinator', 'role': 'CONTACT', 'email': 'cancer@northwestern.edu', 'phone': '312-695-1301'}, {'name': 'William Gradishar, MD', 'role': 'PRINCIPAL_INVESTIGATOR'}], 'facility': 'Northwestern Memorial Hospital', 'geoPoint': {'lat': 41.85003, 'lon': -87.65005}}, {'zip': '02114', 'city': 'Boston', 'state': 'Massachusetts', 'status': 'RECRUITING', 'country': 'United States', 'contacts': [{'name': 'Andreas Varkaris, MD, PhD', 'role': 'CONTACT', 'email': 'avarkaris@mgh.harvard.edu', 'phone': '617-724-4000'}, {'name': 'Andreas Varkaris, MD, PhD', 'role': 'PRINCIPAL_INVESTIGATOR'}], 'facility': 'Massachusetts General Hospital Cancer Center', 'geoPoint': {'lat': 42.35843, 'lon': -71.05977}}, {'zip': '02215', 'city': 'Boston', 'state': 'Massachusetts', 'status': 'RECRUITING', 'country': 'United States', 'contacts': [{'name': 'Susan Gotthardt', 'role': 'CONTACT', 'email': 'sgotthar@bidmc.harvard.edu', 'phone': '617-975-7452'}, {'name': 'Gerburg Wulf, MD', 'role': 'PRINCIPAL_INVESTIGATOR'}], 'facility': 'Beth Israel Deaconess Medical Center', 'geoPoint': {'lat': 42.35843, 'lon': -71.05977}}, {'zip': '02215', 'city': 'Boston', 'state': 'Massachusetts', 'status': 'RECRUITING', 'country': 'United States', 'contacts': [{'name': 'Emily McClure, RN', 'role': 'CONTACT', 'email': 'emily_mcclure@dfci.harvard.edu', 'phone': '857-215-0180'}, {'name': 'Antonio Giordano, MD, PhD', 'role': 'PRINCIPAL_INVESTIGATOR'}], 'facility': 'Dana-Farber Cancer Institute', 'geoPoint': {'lat': 42.35843, 'lon': -71.05977}}, {'zip': '73104', 'city': 'Oklahoma City', 'state': 'Oklahoma', 'status': 'RECRUITING', 'country': 'United States', 'contacts': [{'name': 'Christina Caldwell, LPN', 'role': 'CONTACT', 'email': 'Christina-Caldwell@ouhsc.edu', 'phone': '405-271-8001'}, {'name': 'Debra Richardson, MD', 'role': 'PRINCIPAL_INVESTIGATOR'}], 'facility': 'Stephenson Cancer Center', 'geoPoint': {'lat': 35.46756, 'lon': -97.51643}}, {'zip': '19106', 'city': 'Philadelphia', 'state': 'Pennsylvania', 'status': 'RECRUITING', 'country': 'United States', 'contacts': [{'name': 'Study Coordinator', 'role': 'CONTACT', 'email': 'PAhemoncResearch@uphs.upenn.edu'}, {'name': 'Mark Diamond, MD, PhD', 'role': 'PRINCIPAL_INVESTIGATOR'}], 'facility': 'University of Pennsylvania', 'geoPoint': {'lat': 39.95238, 'lon': -75.16362}}, {'zip': '37232', 'city': 'Nashville', 'state': 'Tennessee', 'status': 'RECRUITING', 'country': 'United States', 'contacts': [{'name': 'Jordan Berlin, MD', 'role': 'CONTACT', 'email': 'CIP@VUMC.ORG', 'phone': '1-800-811-8480'}, {'name': 'Jordan Berlin, MD', 'role': 'PRINCIPAL_INVESTIGATOR'}], 'facility': 'Vanderbilt-Ingram Cancer Center', 'geoPoint': {'lat': 36.16589, 'lon': -86.78444}}, {'zip': '22031', 'city': 'Fairfax', 'state': 'Virginia', 'status': 'RECRUITING', 'country': 'United States', 'contacts': [{'name': 'Carrie Friedman, RN, BSN, OCN', 'role': 'CONTACT', 'email': 'carrie.friedman@usoncology.com', 'phone': '703-636-1473'}, {'name': 'Alexander Spira, MD', 'role': 'PRINCIPAL_INVESTIGATOR'}], 'facility': 'Virginia Cancer Specialists, PC', 'geoPoint': {'lat': 38.84622, 'lon': -77.30637}}, {'zip': '08023', 'city': 'Barcelona', 'status': 'RECRUITING', 'country': 'Spain', 'contacts': [{'name': 'Fabricio Racca, M.D.', 'role': 'CONTACT', 'email': 'fracca@nextoncology.eu', 'phone': '34932746100'}, {'name': 'Fabricio Racca, M.D.', 'role': 'PRINCIPAL_INVESTIGATOR'}], 'facility': 'NEXT Oncology - Hospital Quironsalud Barcelona - PPDS', 'geoPoint': {'lat': 41.38879, 'lon': 2.15899}}, {'zip': '08023', 'city': 'Barcelona', 'status': 'RECRUITING', 'country': 'Spain', 'contacts': [{'name': 'Tatiana Hernandez Guerrero, M.D., Ph.D.', 'role': 'CONTACT', 'email': 'tatiana.hernandez@start-barcelona.com', 'phone': '34915504800'}, {'name': 'Tatiana Hernandez Guerrero, M.D., Ph.D.', 'role': 'PRINCIPAL_INVESTIGATOR'}], 'facility': 'START Barcelona HM Nou Delfos', 'geoPoint': {'lat': 41.38879, 'lon': 2.15899}}, {'zip': '08035', 'city': 'Barcelona', 'status': 'RECRUITING', 'country': 'Spain', 'contacts': [{'name': 'Guzmán Alonso Casal, M.D.', 'role': 'CONTACT', 'email': 'galonso@nextoncology.eu', 'phone': '34932381661'}, {'name': 'Guzmán Alonso Casal, M.D.', 'role': 'PRINCIPAL_INVESTIGATOR'}], 'facility': 'Instituto de Investigacion Oncologica Vall dHebron (VHIO) - EPON', 'geoPoint': {'lat': 41.38879, 'lon': 2.15899}}, {'zip': '28040', 'city': 'Madrid', 'status': 'RECRUITING', 'country': 'Spain', 'contacts': [{'name': 'Jorge Bartolome Arcilla, M.D.', 'role': 'CONTACT', 'email': 'jorge.bartolome@salud.madrid.org', 'phone': '34913303649'}, {'name': 'Jorge Bartolome Arcilla, M.D.', 'role': 'PRINCIPAL_INVESTIGATOR'}], 'facility': 'Hospital Clinico San Carlos', 'geoPoint': {'lat': 40.4165, 'lon': -3.70256}}, {'zip': '28050', 'city': 'Madrid', 'status': 'RECRUITING', 'country': 'Spain', 'contacts': [{'name': 'Bernard Doger, M.D., Ph.D.', 'role': 'CONTACT', 'email': 'bernard.doger@startmadrid.com', 'phone': '34915504800'}, {'name': 'Bernard Doger, M.D, Ph.D.', 'role': 'PRINCIPAL_INVESTIGATOR'}], 'facility': 'START MADRID Hospital Universitario Fundacion Jimenez Diaz - EDOS', 'geoPoint': {'lat': 40.4165, 'lon': -3.70256}}, {'zip': '28050', 'city': 'Madrid', 'status': 'RECRUITING', 'country': 'Spain', 'contacts': [{'name': 'Irene Moreno, M.D.', 'role': 'CONTACT', 'email': 'irene.moreno@startmadrid.com', 'phone': '34917567825'}, {'name': 'Irene Moreno, M.D.', 'role': 'PRINCIPAL_INVESTIGATOR'}], 'facility': 'START MADRID Hospital Universitario HM Sanchinarro - CIOCC', 'geoPoint': {'lat': 40.4165, 'lon': -3.70256}}, {'zip': '31008', 'city': 'Pamplona', 'status': 'RECRUITING', 'country': 'Spain', 'contacts': [{'name': 'Jose Maria Lopez Picazo, M.D.', 'role': 'CONTACT', 'email': 'jlpicazo@unav.es', 'phone': '34948255400'}, {'name': 'Jose Maria Lopez Picazo, M.D.', 'role': 'PRINCIPAL_INVESTIGATOR'}], 'facility': 'Clinica Universidad de Navarra', 'geoPoint': {'lat': 42.81687, 'lon': -1.64323}}, {'zip': '28223', 'city': 'Pozuelo de Alarcón', 'status': 'RECRUITING', 'country': 'Spain', 'contacts': [{'name': 'Valentina Boni, M.D.', 'role': 'CONTACT', 'email': 'vboni@nextoncology.eu', 'phone': '34914521900'}, {'name': 'Valentina Boni, M.D.', 'role': 'PRINCIPAL_INVESTIGATOR'}], 'facility': 'NEXT Oncology - Hospital Quironsalud Madrid - PPDS', 'geoPoint': {'lat': 40.43293, 'lon': -3.81338}}, {'zip': '46010', 'city': 'Valencia', 'status': 'RECRUITING', 'country': 'Spain', 'contacts': [{'name': 'Valentina Gambardella, M.D., Ph.D.', 'role': 'CONTACT', 'email': 'vgambardella@incliva.es', 'phone': '34961973528'}, {'name': 'Valentina Gambardella, M.D., Ph.D.', 'role': 'PRINCIPAL_INVESTIGATOR'}], 'facility': 'Hospital Clinico Universitario de Valencia', 'geoPoint': {'lat': 39.47391, 'lon': -0.37966}}], 'centralContacts': [{'name': 'Clinical Trials', 'role': 'CONTACT', 'email': 'clinicaltrials@totusmedicines.com', 'phone': 'Please e-mail'}], 'overallOfficials': [{'name': 'Zelanna Goldberg, MD', 'role': 'STUDY_DIRECTOR', 'affiliation': 'Totus Medicines'}]}, 'ipdSharingStatementModule': {'ipdSharing': 'NO'}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'Totus Medicines', 'class': 'INDUSTRY'}, 'responsibleParty': {'type': 'SPONSOR'}}}}