Ignite Creation Date:
2025-12-25 @ 4:57 AM
Ignite Modification Date:
2025-12-26 @ 3:57 AM
Study NCT ID:
NCT04159818
Status:
RECRUITING
Last Update Posted:
2022-03-22
First Post:
2019-10-23
Is NOT Gene Therapy:
False
Has Adverse Events:
False
Brief Title:
Immune Induction Strategies to Improve Response to Immune Checkpoint Blockade in Triple Negative Breast Cancer (TNBC) Patients
Sponsor:
Organization:
Raw JSON
{'hasResults': False, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'conditionBrowseModule': {'meshes': [{'id': 'D001943', 'term': 'Breast Neoplasms'}, {'id': 'D009362', 'term': 'Neoplasm Metastasis'}], 'ancestors': [{'id': 'D009371', 'term': 'Neoplasms by Site'}, {'id': 'D009369', 'term': 'Neoplasms'}, {'id': 'D001941', 'term': 'Breast Diseases'}, {'id': 'D012871', 'term': 'Skin Diseases'}, {'id': 'D017437', 'term': 'Skin and Connective Tissue Diseases'}, {'id': 'D009385', 'term': 'Neoplastic Processes'}, {'id': 'D010335', 'term': 'Pathologic Processes'}, {'id': 'D013568', 'term': 'Pathological Conditions, Signs and Symptoms'}]}, 'interventionBrowseModule': {'meshes': [{'id': 'D000077594', 'term': 'Nivolumab'}, {'id': 'D002945', 'term': 'Cisplatin'}, {'id': 'D004317', 'term': 'Doxorubicin'}], 'ancestors': [{'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': 'D000602', 'term': 'Amino Acids, Peptides, and Proteins'}, {'id': 'D012712', 'term': 'Serum Globulins'}, {'id': 'D005916', 'term': 'Globulins'}, {'id': 'D017606', 'term': 'Chlorine Compounds'}, {'id': 'D007287', 'term': 'Inorganic Chemicals'}, {'id': 'D017672', 'term': 'Nitrogen Compounds'}, {'id': 'D017671', 'term': 'Platinum Compounds'}, {'id': 'D003630', 'term': 'Daunorubicin'}, {'id': 'D018943', 'term': 'Anthracyclines'}, {'id': 'D009279', 'term': 'Naphthacenes'}, {'id': 'D011084', 'term': 'Polycyclic Aromatic Hydrocarbons'}, {'id': 'D006841', 'term': 'Hydrocarbons, Aromatic'}, {'id': 'D006844', 'term': 'Hydrocarbons, Cyclic'}, {'id': 'D006838', 'term': 'Hydrocarbons'}, {'id': 'D009930', 'term': 'Organic Chemicals'}, {'id': 'D011083', 'term': 'Polycyclic Compounds'}, {'id': 'D000617', 'term': 'Aminoglycosides'}, {'id': 'D006027', 'term': 'Glycosides'}, {'id': 'D002241', 'term': 'Carbohydrates'}]}}, 'protocolSection': {'designModule': {'phases': ['PHASE2'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'RANDOMIZED', 'maskingInfo': {'masking': 'NONE', 'maskingDescription': 'Patients are randomized between experimental cohorts and a control cohort.'}, 'primaryPurpose': 'TREATMENT', 'interventionModel': 'PARALLEL', 'interventionModelDescription': 'Patients are randomized between experimental cohorts and a control cohort.'}, 'enrollmentInfo': {'type': 'ESTIMATED', 'count': 52}}, 'statusModule': {'overallStatus': 'RECRUITING', 'startDateStruct': {'date': '2020-02-21', 'type': 'ACTUAL'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2022-03', 'completionDateStruct': {'date': '2026-12-15', 'type': 'ESTIMATED'}, 'lastUpdateSubmitDate': '2022-03-21', 'studyFirstSubmitDate': '2019-10-23', 'studyFirstSubmitQcDate': '2019-11-07', 'lastUpdatePostDateStruct': {'date': '2022-03-22', 'type': 'ACTUAL'}, 'studyFirstPostDateStruct': {'date': '2019-11-12', 'type': 'ACTUAL'}, 'primaryCompletionDateStruct': {'date': '2022-12-15', 'type': 'ESTIMATED'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'Progression free survival', 'timeFrame': 'assessed monthly until progression or date of death; median 12 months', 'description': 'Time from randomization to date of first tumor progression'}], 'secondaryOutcomes': [{'measure': 'Overall response rate', 'timeFrame': 'assessed at week 6, 12 and 20 and every 8 weeks thereafter; assessed up to 120 months', 'description': 'complete response or partial response according to iRECIST and RECIST1.1'}, {'measure': 'Clinical benefit rate', 'timeFrame': 'assessed at week 6, 12 and 20 and every 8 weeks thereafter; assessed up to 120 months', 'description': 'Beneficial response (complete response, partial response or stable disease) according to RECIST 1.1 and iRECIST'}, {'measure': 'Overall survival', 'timeFrame': 'assessed monthly until date of death; median 12 months', 'description': 'time from nivolumab initiation to death from any cause'}, {'measure': 'Toxicity of all study regimens', 'timeFrame': 'assessed until 100 days after of treatment end', 'description': 'adverse events will be graded according to NCI Common Toxicity Criteria v 5.0'}, {'measure': 'Progression Free Survival after 6 cycles', 'timeFrame': 'time from nivolumab initiation to tumor progression or death from any cause; assessed up to 120 months', 'description': 'the number of patients free of progression after 6 cycles of nivolumab'}]}, 'oversightModule': {'oversightHasDmc': False, 'isFdaRegulatedDrug': False, 'isFdaRegulatedDevice': False}, 'conditionsModule': {'keywords': ['Triple negative', 'Metastatic disease'], 'conditions': ['Metastatic Breast Cancer']}, 'descriptionModule': {'briefSummary': "This is a single center non-blinded randomized multi-cohort non-comparative phase II trial with a Simon's two-stage design.", 'detailedDescription': 'In the first stage, 13 evaluable patients will be accrued per cohort. Evaluable is defined as: at least one administration of nivolumab and availability of paired biopsies for immunohistochemistry (for induction treatment cohorts pre-induction and pre-nivolumab biopsies).\n\nIf there are 1 or no responses observed in these 13 patients, the cohort will be stopped. Otherwise, 21 additional patients will be accrued for a total of 34.'}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['ADULT', 'OLDER_ADULT'], 'minimumAge': '18 Years', 'healthyVolunteers': False, 'eligibilityCriteria': 'Inclusion Criteria:\n\n* Metastatic or incurable locally advanced triple negative breast cancer (ER \\< 10%, HER2 IHC 0,1+ or 2+ with no amplification)\n* Metastatic lesion accessible for histological biopsy\n* 18 years or older\n* Maximum of three lines of chemotherapy for metastatic disease and with evidence of progression of disease. Treatment with low-dose doxorubicin in the palliative setting is not allowed.\n* WHO performance status of 0 or 1\n* Measurable or evaluable disease according to RECIST 1.1\n* Disease Free Interval (defined as time between first diagnosis or locoregional recurrence and first metastasis) longer than 1 year\n* Subjects with brain metastases are eligible if these are not symptomatic and free of progression of at least 4 weeks\n* A maximum dosage of 360 mg/m2 of anthracyclines and no previous anthracycline-related cardiac toxicity. In case of radiation in the cardiac area, hypertension, diabetes mellitus or hypercholesterolemia, the left ventricular ejection fraction must be 50% or higher.\n* Adequate bone marrow, kidney and liver function\n\nExclusion Criteria:\n\n* uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris\n* known history of leptomeningeal disease localization\n* history of having received other anticancer therapies within 2 weeks of start of the study drug\n* history of immunodeficiency, autoimmune disease, conditions requiring immunosuppression (\\>10 mgl daily prednisone equivalents) or chronic infections.\n* prior treatment with immune checkpoint inhibitors.\n* active other cancer\n* history of uncontrolled serious medical or psychiatric illness\n* current pregnancy or breastfeeding'}, 'identificationModule': {'nctId': 'NCT04159818', 'acronym': 'TONIC-2', 'briefTitle': 'Immune Induction Strategies to Improve Response to Immune Checkpoint Blockade in Triple Negative Breast Cancer (TNBC) Patients', 'organization': {'class': 'OTHER', 'fullName': 'The Netherlands Cancer Institute'}, 'officialTitle': 'Immune Induction Strategies to Improve Response to Immune Checkpoint Blockade in Triple Negative Breast Cancer (TNBC) Patients: the TONIC-2 Trial', 'orgStudyIdInfo': {'id': 'N19TON'}}, 'armsInterventionsModule': {'armGroups': [{'type': 'EXPERIMENTAL', 'label': 'Control group', 'description': 'no induction treatment, nivolumab 240 mg flat-dose, every 2 weeks', 'interventionNames': ['Drug: Nivolumab']}, {'type': 'EXPERIMENTAL', 'label': 'Cisplatin induction', 'description': 'Cisplatin 40mg/m2, weekly for two weeks, after 2 weeks followed by nivolumab 240 mg flat-dose, every 2 weeks', 'interventionNames': ['Drug: Nivolumab', 'Drug: Cisplatin']}, {'type': 'EXPERIMENTAL', 'label': 'Low dose doxorubicin induction', 'description': 'Low dose doxorubicin 15mg flat dose, weekly for 8 weeks, after 2 weeks followed by nivolumab 240 mg flat-dose, every 2 weeks', 'interventionNames': ['Drug: Nivolumab', 'Drug: Low dose doxorubicin']}], 'interventions': [{'name': 'Nivolumab', 'type': 'DRUG', 'description': '240 mg flat-dose, every 2 weeks. From 20 weeks onwards, nivolumab will be administered every 4 weeks with a flat-dose of 480 mg starting from week 20 onwards', 'armGroupLabels': ['Cisplatin induction', 'Control group', 'Low dose doxorubicin induction']}, {'name': 'Cisplatin', 'type': 'DRUG', 'description': '40mg/m2, weekly for two weeks', 'armGroupLabels': ['Cisplatin induction']}, {'name': 'Low dose doxorubicin', 'type': 'DRUG', 'description': '15mg flat dose, weekly for 8 weeks', 'armGroupLabels': ['Low dose doxorubicin induction']}]}, 'contactsLocationsModule': {'locations': [{'zip': '1066 CX', 'city': 'Amsterdam', 'status': 'RECRUITING', 'country': 'Netherlands', 'contacts': [{'name': 'Marleen Kok, MD', 'role': 'CONTACT', 'email': 'm.kok@nki.nl', 'phone': '+3120512', 'phoneExt': '9111'}, {'name': 'Ingrid AM Mandjes, MSc', 'role': 'CONTACT', 'email': 'i.mandjes@nki.nl', 'phone': '+3120512', 'phoneExt': '9111'}, {'name': 'Marleen kok, MD', 'role': 'PRINCIPAL_INVESTIGATOR'}], 'facility': 'Antoni van Leeuwenhoek', 'geoPoint': {'lat': 52.37403, 'lon': 4.88969}}], 'centralContacts': [{'name': 'Marleen Kok, MD', 'role': 'CONTACT', 'email': 'm.kok@nki.nl', 'phone': '+3120 512', 'phoneExt': '9111'}, {'name': 'Leonie Voorwerk, MD', 'role': 'CONTACT', 'email': 'l.voorwerk@nki.nl', 'phone': '+3120 512', 'phoneExt': '9111'}], 'overallOfficials': [{'name': 'Marleen Kok, MD', 'role': 'PRINCIPAL_INVESTIGATOR', 'affiliation': 'NKI-AvL'}]}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'The Netherlands Cancer Institute', 'class': 'OTHER'}, 'collaborators': [{'name': 'Bristol-Myers Squibb', 'class': 'INDUSTRY'}], 'responsibleParty': {'type': 'SPONSOR'}}}}