Ignite Creation Date:
2026-03-26 @ 3:16 PM
Ignite Modification Date:
2026-04-07 @ 3:31 AM
Study NCT ID:
NCT07404332
Status:
NOT_YET_RECRUITING
Last Update Posted:
2026-02-11
First Post:
2026-02-04
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
5-Azacitidine Plus PD-1/PD-L1 Inhibitor With PD-1/PD-L1 Refractory Tumors
Sponsor:
Organization:
Raw JSON
{'hasResults': False, 'derivedSection': {'miscInfoModule': {'versionHolder': '2026-03-25'}, 'conditionBrowseModule': {'meshes': [{'id': 'D009362', 'term': 'Neoplasm Metastasis'}], 'ancestors': [{'id': 'D009385', 'term': 'Neoplastic Processes'}, {'id': 'D009369', 'term': 'Neoplasms'}, {'id': 'D010335', 'term': 'Pathologic Processes'}, {'id': 'D013568', 'term': 'Pathological Conditions, Signs and Symptoms'}]}, 'interventionBrowseModule': {'meshes': [{'id': 'D001374', 'term': 'Azacitidine'}, {'id': 'C582435', 'term': 'pembrolizumab'}, {'id': 'D000077594', 'term': 'Nivolumab'}, {'id': 'C000627974', 'term': 'cemiplimab'}], 'ancestors': [{'id': 'D001372', 'term': 'Aza Compounds'}, {'id': 'D009930', 'term': 'Organic Chemicals'}, {'id': 'D003562', 'term': 'Cytidine'}, {'id': 'D011741', 'term': 'Pyrimidine Nucleosides'}, {'id': 'D011743', 'term': 'Pyrimidines'}, {'id': 'D006573', 'term': 'Heterocyclic Compounds, 1-Ring'}, {'id': 'D006571', 'term': 'Heterocyclic Compounds'}, {'id': 'D009705', 'term': 'Nucleosides'}, {'id': 'D009706', 'term': 'Nucleic Acids, Nucleotides, and Nucleosides'}, {'id': 'D012263', 'term': 'Ribonucleosides'}, {'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'}]}}, 'protocolSection': {'designModule': {'phases': ['PHASE1'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'NA', 'maskingInfo': {'masking': 'NONE'}, 'primaryPurpose': 'TREATMENT', 'interventionModel': 'SINGLE_GROUP'}, 'enrollmentInfo': {'type': 'ESTIMATED', 'count': 35}}, 'statusModule': {'overallStatus': 'NOT_YET_RECRUITING', 'startDateStruct': {'date': '2026-02-28', 'type': 'ESTIMATED'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2026-02', 'completionDateStruct': {'date': '2031-02-28', 'type': 'ESTIMATED'}, 'lastUpdateSubmitDate': '2026-02-04', 'studyFirstSubmitDate': '2026-02-04', 'studyFirstSubmitQcDate': '2026-02-04', 'lastUpdatePostDateStruct': {'date': '2026-02-11', 'type': 'ACTUAL'}, 'studyFirstPostDateStruct': {'date': '2026-02-11', 'type': 'ACTUAL'}, 'primaryCompletionDateStruct': {'date': '2028-02-28', 'type': 'ESTIMATED'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'Incidence of dose-limiting toxicities and responses as defined by CTCAE v5.0', 'timeFrame': 'Treatment initiation through 30 days +/- 7 days post completion of therapy', 'description': 'Assess the safety and tolerability of 5-Azacitidine Plus PD-1/PD-L1 inhibitor'}], 'secondaryOutcomes': [{'measure': 'Proportion of participants with a complete response (CR)', 'timeFrame': 'Treatment initiation through five years', 'description': 'The proportion of patients with a pathologic complete response, defined as disappearance of all target lesions, disappearance of all non-target lesions and normalization of tumor marker level'}, {'measure': 'Proportion of participants with a partial response (PR)', 'timeFrame': 'Treatment initiation through five years', 'description': 'At least a 30% decrease in the sum of the LD of target lesions, taking as reference the baseline sum LD'}, {'measure': 'Overall Survival (OS)', 'timeFrame': 'Treatment initiation through five years', 'description': 'Time from study treatment initiation to death due to any cause'}, {'measure': 'Progression Free Survival (PFS)', 'timeFrame': 'Treatment initiation through five years', 'description': 'Time from study treatment initiation to disease progression or death due to any cause'}]}, 'oversightModule': {'oversightHasDmc': True, 'isFdaRegulatedDrug': True, 'isFdaRegulatedDevice': False}, 'conditionsModule': {'conditions': ['Solid Tumor', 'Locally Advanced Solid Tumor', 'Metastatic Tumor']}, 'descriptionModule': {'briefSummary': 'This is a Phase I study to determine the optimal biological dose (OBD) of 5-Azacitidine in combination with PD-1/PD-L1 inhibitors in patients with tumors refractory to PD-1/PD-L1 inhibitors, for which such treatments have been approved.', 'detailedDescription': 'This is a Phase I study to determine the optimal biological dose (OBD) of 5-Azacitidine in combination with PD-1/PD-L1 inhibitors in patients with tumors refractory to PD-1/PD-L1 inhibitors, for which such treatments have been approved.\n\nThis Phase I study will assess 6 doses of 5-Azacitidine (5, 10, 15, 25, 50 and 75 mg/m2) in combination with a PD1/PD-L1 inhibitor. The PD1/PD-L1 inhibitor will be given at standard of care dosing approved by the FDA for this indication.'}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['ADULT', 'OLDER_ADULT'], 'maximumAge': '99 Years', 'minimumAge': '18 Years', 'healthyVolunteers': False, 'eligibilityCriteria': "Inclusion Criteria:\n\n* Written and voluntary informed consent.\n* At least 18 years of age or older.\n* Histologically and radiologically confirmed locally advanced or metastatic unresectable solid tumor malignancy for which PD-1 or PD-L1 therapy is already approved by the FDA. Locally advanced is defined as unresectable in the opinion of the treating physician. A repeat biopsy is required if previous biopsy tissue is unavailable.\n* At least one Response Evaluation Criteria in Solid Tumors (RECIST 1.1) - defined target lesion.\n* Eastern Cooperative Oncology Group (ECOG) performance status of 0 (fully active, able to carry on all pre-disease performance without restriction), 1 (restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature, such as light housework or office work), or 2 (ambulatory and capable of self-care but unable to carry out any work activities, spending more than 50% of waking hours up and about).\n* Documented progression on PD1 or PD-L1 inhibitors.\n* Recovery from any acute toxicity associated with prior therapy to grade 1.\n* Renal function (creatinine level within normal institutional limit, or creatinine clearance \\>15 mL/min/1.73 m2 for patients with creatinine levels above institutional normal, calculated using the Cockcroft-Gault formula).\n* Liver function (AST/ALT \\<3.0 X institutional upper limit of normal OR \\<5 X institutional upper limit of normal in cases of liver metastasis; total bilirubin ≤ 1.5 times upper limit of normal).\n* Adequate hematological lab values including:\n\n * Absolute Neutrophil Count (ANC) ≥ 1.0 X 109/L\n * Platelets ≥ 100X109/L\n * Hemoglobin ≥ 7.0 g/dL\n* Female subjects of childbearing potential and non-sterilized male subjects who intend to be sexually active during the study must agree to use a highly effective method of contraception from time of screening, throughout the whole duration of the drug treatment, and during the 6-month post-treatment washout period.\n* Patients may have previously received a hypomethylating agent, as long as it was not given in combination with ipilimumab.\n* Patients may have previously received ipilimumab but must have relapsed or progressed while on therapy.\n* Patients must have adequate archival tissue available for the purpose of downstream methylation status assessment, immunohistochemistry, RNA expression (10 slides at 5µM). If archival tissue is not available, a repeat biopsy is required.\n\nExclusion Criteria:\n\n* Patients with a prior or concurrent malignancy whose natural history or treatment has the potential to interfere with the safety or efficacy assessment of the investigational regimen.\n* Patients with active, untreated metastases in the central nervous system.\n* Patients who are pregnant or breastfeeding.\n* Patients who have an active infection.\n* Patients with significant hematologic, hepatic, and renal function impairment.\n* Patients who are being treated for any concurrent medical condition requiring the use of systemic steroids or history of long-term use of systemic steroids.\n* Patients who have a history of inflammatory bowel disease or a history of symptomatic autoimmune disease.\n* Patients who have had any major surgical procedure or significant traumatic injury within 28 days prior to study enrollment.\n* Patients who have received chemotherapy, immunosuppressive agents or any investigational drug within 28 days prior to starting the study drugs.\n* Patients who have any underlying medical condition which, in the treating physician's opinion, will make the administration of study drugs hazardous or obscure the interpretation of adverse events."}, 'identificationModule': {'nctId': 'NCT07404332', 'briefTitle': '5-Azacitidine Plus PD-1/PD-L1 Inhibitor With PD-1/PD-L1 Refractory Tumors', 'organization': {'class': 'OTHER', 'fullName': 'University of Iowa'}, 'officialTitle': 'Phase I Study of 5-Azacitidine Plus PD-1/PD-L1 Inhibitor in Patients With PD-1/PD-L1 Refractory Tumors', 'orgStudyIdInfo': {'id': '202511023'}}, 'armsInterventionsModule': {'armGroups': [{'type': 'EXPERIMENTAL', 'label': '5-Azacitidine Plus PD-1/PD-L1 inhibitor', 'description': 'This Phase I study will assess 6 doses of 5-Azacitidine (5, 10, 15, 25, 50 and 75 mg/m2) in combination with a PD1/PD-L1 inhibitor. The PD1/PD-L1 inhibitor will be given at standard of care dosing approved by the FDA for this indication. Inhibitors approved for study indications include Pembrolizumab, Nivolumab, and Cemiplimab.', 'interventionNames': ['Drug: 5 Azacytidine', 'Drug: Pembrolizumab', 'Drug: Nivolumab', 'Drug: Cemiplimab']}], 'interventions': [{'name': '5 Azacytidine', 'type': 'DRUG', 'description': '5-Azacitidine (Azacitidine) is a nucleoside analogue chemotherapy drug', 'armGroupLabels': ['5-Azacitidine Plus PD-1/PD-L1 inhibitor']}, {'name': 'Pembrolizumab', 'type': 'DRUG', 'description': 'Pembrolizumab is a high-affinity humanized monoclonal antibody that functions as immune checkpoint inhibitor', 'armGroupLabels': ['5-Azacitidine Plus PD-1/PD-L1 inhibitor']}, {'name': 'Nivolumab', 'type': 'DRUG', 'description': 'Nivolumab is a high-affinity humanized monoclonal antibody that functions as immune checkpoint inhibitor', 'armGroupLabels': ['5-Azacitidine Plus PD-1/PD-L1 inhibitor']}, {'name': 'Cemiplimab', 'type': 'DRUG', 'description': 'Cemiplimab is a high-affinity humanized monoclonal antibody that functions as immune checkpoint inhibitor', 'armGroupLabels': ['5-Azacitidine Plus PD-1/PD-L1 inhibitor']}]}, 'contactsLocationsModule': {'locations': [{'zip': '52242', 'city': 'Iowa City', 'state': 'Iowa', 'country': 'United States', 'contacts': [{'name': 'Mohammed Milhem, MD', 'role': 'CONTACT', 'email': 'mohammed-milhem@uiowa.edu', 'phone': '+1 319 356 2324'}, {'name': 'Milhem', 'role': 'CONTACT'}], 'facility': 'University of Iowa Health Care', 'geoPoint': {'lat': 41.66113, 'lon': -91.53017}}], 'centralContacts': [{'name': 'Mohammed Milhem, MD', 'role': 'CONTACT', 'email': 'mohammed-milhem@uiowa.edu', 'phone': '+1 319 356 2324'}], 'overallOfficials': [{'name': 'Mohammed Milhem, MD', 'role': 'PRINCIPAL_INVESTIGATOR', 'affiliation': 'University of Iowa'}]}, 'ipdSharingStatementModule': {'ipdSharing': 'NO'}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'Mohammed Milhem', 'class': 'OTHER'}, 'responsibleParty': {'type': 'SPONSOR_INVESTIGATOR', 'investigatorTitle': 'Clinical Professor', 'investigatorFullName': 'Mohammed Milhem', 'investigatorAffiliation': 'University of Iowa'}}}}