Ignite Creation Date:
2026-03-26 @ 3:19 PM
Ignite Modification Date:
2026-03-30 @ 2:54 AM
Study NCT ID:
NCT07492394
Status:
RECRUITING
Last Update Posted:
2026-03-25
First Post:
2025-12-04
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
Dalpiciclib With or Without Entinostat and Letrozole in HR+/HER2- Early Breast Cancer
Sponsor:
Organization:
Raw JSON
{'hasResults': False, 'derivedSection': {'miscInfoModule': {'versionHolder': '2026-03-25'}, 'conditionBrowseModule': {'meshes': [{'id': 'D001943', 'term': 'Breast Neoplasms'}], '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'}]}, 'interventionBrowseModule': {'meshes': [{'id': 'C118739', 'term': 'entinostat'}, {'id': 'D056572', 'term': 'Histone Deacetylase Inhibitors'}, {'id': 'C000720752', 'term': 'dalpiciclib'}, {'id': 'D000077289', 'term': 'Letrozole'}], 'ancestors': [{'id': 'D004791', 'term': 'Enzyme Inhibitors'}, {'id': 'D045504', 'term': 'Molecular Mechanisms of Pharmacological Action'}, {'id': 'D020228', 'term': 'Pharmacologic Actions'}, {'id': 'D020164', 'term': 'Chemical Actions and Uses'}, {'id': 'D009570', 'term': 'Nitriles'}, {'id': 'D009930', 'term': 'Organic Chemicals'}, {'id': 'D014230', 'term': 'Triazoles'}, {'id': 'D001393', 'term': 'Azoles'}, {'id': 'D006573', 'term': 'Heterocyclic Compounds, 1-Ring'}, {'id': 'D006571', 'term': 'Heterocyclic Compounds'}]}}, 'protocolSection': {'designModule': {'phases': ['PHASE2'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'NON_RANDOMIZED', 'maskingInfo': {'masking': 'NONE'}, 'primaryPurpose': 'TREATMENT', 'interventionModel': 'PARALLEL'}, 'enrollmentInfo': {'type': 'ESTIMATED', 'count': 60}}, 'statusModule': {'overallStatus': 'RECRUITING', 'startDateStruct': {'date': '2025-09-12', 'type': 'ACTUAL'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2025-09', 'completionDateStruct': {'date': '2031-12-31', 'type': 'ESTIMATED'}, 'lastUpdateSubmitDate': '2026-03-19', 'studyFirstSubmitDate': '2025-12-04', 'studyFirstSubmitQcDate': '2026-03-19', 'lastUpdatePostDateStruct': {'date': '2026-03-25', 'type': 'ACTUAL'}, 'studyFirstPostDateStruct': {'date': '2026-03-25', 'type': 'ACTUAL'}, 'primaryCompletionDateStruct': {'date': '2026-12-31', 'type': 'ESTIMATED'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'ORR', 'timeFrame': 'From baseline to end of neoadjuvant therapy (approximately 6 cycles, ~24 weeks', 'description': 'Objective Response Rate (ORR) is defined as the proportion of participants who achieve a complete response (CR) or partial response (PR) as assessed according to RECIST v1.1 criteria. Tumor response must be confirmed by repeat imaging at least 4 weeks after the initial documentation of response.'}], 'secondaryOutcomes': [{'measure': 'tpCR', 'timeFrame': 'At the time of definitive surgery (approximately 18-24 weeks after initiation of neoadjuvant therapy)', 'description': 'Total pathological complete response (tpCR) is defined as the absence of residual invasive cancer in both the breast and axillary lymph nodes following neoadjuvant therapy, corresponding to ypT0/Tis, ypN0.'}, {'measure': 'Breast-conserving surgery (BCS) rate', 'timeFrame': 'At the time of definitive surgery', 'description': 'Breast-conserving surgery rate is defined as the proportion of participants who undergo breast-conserving surgery (lumpectomy) among all participants who proceed to definitive breast surgery after completion of neoadjuvant therapy. The classification of breast-conserving surgery is based on the operative report and pathology assessment.'}, {'measure': 'Proportion of participants achieving PEPI 0', 'timeFrame': 'At the time of definitive surgery', 'description': 'PEPI 0 (Preoperative Endocrine Prognostic Index score of 0) is defined as meeting all of the following criteria at surgery after completion of neoadjuvant endocrine-based therapy:\n\nPathologic tumor size: ypT1 or smaller (≤2 cm)\n\nNodal status: ypN0 (no metastatic involvement in regional lymph nodes)\n\nKi-67 proliferation index: ≤2.7% in the surgical specimen\n\nEstrogen receptor (ER): Allred score of 3-8 (ER-positive)\n\nParticipants meeting all components are classified as achieving PEPI score = 0, indicating an extremely low risk of relapse.'}]}, 'oversightModule': {'oversightHasDmc': False, 'isFdaRegulatedDrug': False, 'isFdaRegulatedDevice': False}, 'conditionsModule': {'conditions': ['Breast Cancer']}, 'descriptionModule': {'briefSummary': "Brief Summary This is an open-label, randomized, phase II clinical study designed to evaluate neoadjuvant treatment regimens in patients with hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) early breast cancer.\n\nA total of 60 premenopausal, perimenopausal, and postmenopausal patients with HR+/HER2- breast cancer who meet the inclusion criteria will be enrolled. During the study, clinical information will be collected according to standard practice, including demographic data, tumor imaging, and pathological results (e.g., Ki-67). Investigator-assessed outcomes will be used as the final results.\n\nAfter 14 days of treatment, patients who provide consent will undergo a second biopsy to evaluate the rate of complete cell-cycle arrest. Safety assessments and imaging evaluations will be performed at treatment completion or upon study withdrawal. Informed consent must be obtained at each study center before participation.\n\nTreatment arms:\n\nArm A (30 patients):\n\nDalpiciclib 125 mg orally once daily on Days 1-21 of each 28-day cycle (3 weeks on, 1 week off), for 6 cycles Letrozole 2.5 mg orally once daily continuously for 6 cycles Entinostat 3 mg orally once weekly (Days 1-28 of each 28-day cycle), for 6 cycles\n\nArm B (30 patients):\n\nDalpiciclib 150 mg orally once daily on Days 1-21 of each 28-day cycle, for 6 cycles Letrozole 2.5 mg orally once daily continuously for 6 cycles Premenopausal and perimenopausal women will also receive ovarian function suppression (OFS), such as with a GnRHa agent.\n\nAfter signing informed consent, patients will begin neoadjuvant therapy with dalpiciclib plus entinostat and letrozole ± OFS. Ultrasound assessments will be conducted every two treatment cycles and before surgery under the same imaging conditions as baseline. Bone scans will be performed at the end of neoadjuvant treatment. MRI of the breast will be performed at baseline, after two cycles, and before surgery to assess treatment efficacy. Treatment discontinuation will occur if toxicity is intolerable, consent is withdrawn, or the investigator determines it is necessary.\n\nAdjuvant therapy:\n\nAfter surgery, patients will receive physician's choice of therapy (TPC).\n\nSafety follow-up:\n\nPatients will be followed until they start another anticancer therapy, all adverse events have resolved to Grade 0-1 or baseline level, or death-whichever occurs first.", 'detailedDescription': 'For patients with HR-positive, HER2-negative early or locally advanced breast cancer, achieving a clinical complete response with traditional neoadjuvant chemotherapy is challenging, and treatment tolerance is often suboptimal. Endocrine therapy plays an important role in both early-stage and advanced HR+/HER2- breast cancer; however, its efficacy in the neoadjuvant setting remains to be further clarified. Existing studies have shown that, compared with neoadjuvant chemotherapy, neoadjuvant endocrine therapy in HR+/HER2- breast cancer yields comparable clinical complete response and breast-conserving surgery rates, with substantially lower toxicity. Therefore, strategies to further improve response to neoadjuvant endocrine therapy may be more meaningful than intensifying chemotherapy in this population.\n\nWith the clinical availability of CDK4/6 inhibitors, the efficacy of neoadjuvant endocrine therapy has been further improved. Results from DAWNA-1, DAWNA-2, and DAWNA-A have strengthened the evidence base supporting the use of the domestically developed CDK4/6 inhibitor dalpiciclib in the adjuvant treatment of breast cancer.\n\nHowever, some studies have found that increased histone deacetylase (HDAC) activity in the estrogen receptor (ER) promoter region can suppress ER expression and lead to endocrine therapy resistance. Entinostat is an oral HDAC inhibitor that selectively inhibits class I (primarily HDAC1 and HDAC3) and class IV HDACs. In the phase III study EOC103A3101 conducted in China, entinostat significantly improved median progression-free survival (PFS) compared with placebo (6.32 vs. 3.72 months), reducing the risk of disease progression or death by 24% (HR 0.76). Median overall survival (OS) was also prolonged in the entinostat group (38.39 months), with a 17% reduction in mortality risk (HR 0.83), demonstrating clinically meaningful survival benefits.\n\nBased on these findings, the present study aims to further evaluate whether the combination of dalpiciclib, entinostat, and letrozole as neoadjuvant therapy for patients with HR-positive, HER2-negative early breast cancer may provide an improved clinical strategy compared with current standards.'}, 'eligibilityModule': {'sex': 'FEMALE', 'stdAges': ['ADULT', 'OLDER_ADULT'], 'maximumAge': '75 Years', 'minimumAge': '18 Years', 'genderBased': True, 'genderDescription': 'Postmenopausal or premenopausal/perimenopausal female patients aged ≥18 years and \\<75 years.', 'healthyVolunteers': False, 'eligibilityCriteria': "Inclusion Criteria:\n\n\\- Inclusion Criteria\n\nFemale patients aged ≥18 and \\<75 years, including postmenopausal, premenopausal, or perimenopausal. Postmenopause is defined as:\n\nPrior bilateral oophorectomy, or age ≥60 years; or\n\nAge \\<60 years, natural postmenopause (spontaneous cessation of menses for ≥12 months without other pathological or physiological cause) with estradiol (E2) and FSH in postmenopausal range; or\n\nPremenopausal or perimenopausal women willing to receive LHRH agonist (OFS) therapy during the study.\n\nHistologically confirmed estrogen receptor (ER)-positive (\\>10%) invasive breast cancer, regardless of PR expression, and HER2-negative according to the 2018 ASCO/CAP HER2 testing guidelines (IHC 0+ or IHC 2+ with ISH-negative, amplification ratio \\<2.0).\n\nAt least one measurable lesion according to RECIST 1.1; clinical stage T1c-T2, cN1-2, or T3-T4, cN0-2.\n\nNo prior anticancer therapy for breast cancer, including chemotherapy, endocrine therapy, or targeted therapy.\n\nAbility to swallow oral medications.\n\nBaseline left ventricular ejection fraction (LVEF) ≥50%.\n\nAdequate organ function:\n\nHematology (within 1 week):\n\nAbsolute neutrophil count (ANC) ≥1.5 × 10⁹/L\n\nWhite blood cell count (WBC) ≥3.0 × 10⁹/L\n\nPlatelet count ≥90 × 10⁹/L\n\nHemoglobin ≥90 g/L\n\nLiver and kidney function (within 1 week):\n\nTotal bilirubin (TBIL) ≤ upper limit of normal (ULN)\n\nALT and AST ≤1.5 × ULN\n\nBUN and creatinine ≤1.5 × ULN, with creatinine clearance ≥60 mL/min (Cockcroft-Gault formula)\n\nECG: Corrected QT interval ≤470 ms (12-lead ECG)\n\nWillingness and ability to undergo all required biopsy procedures.\n\nWomen of childbearing potential must have a negative pregnancy test before study entry and agree to use medically acceptable contraception during the study; postmenopausal women are exempt.\n\nVoluntary participation with signed informed consent, good compliance, and willingness to adhere to follow-up requirements.\n\nExclusion Criteria:\n\n\\- Exclusion Criteria\n\nPregnant or breastfeeding women, or women with a positive pregnancy test at baseline; women of childbearing potential unwilling to use effective contraception during the study.\n\nBilateral breast cancer or inflammatory breast cancer.\n\nStage IV (metastatic) breast cancer at initial diagnosis.\n\nHistory of congestive heart failure, unstable angina, significant arrhythmia, or myocardial infarction.\n\nActive pulmonary disease, including interstitial lung disease, pneumonia, pulmonary fibrosis, or other acute lung conditions.\n\nSignificant liver disease, such as acute or fulminant hepatitis, impaired coagulation factor synthesis, or other severe hepatic dysfunction.\n\nFor patients positive for HBsAg or HBV core antibody, peripheral blood HBV DNA must be \\<1×10³ IU/mL to be eligible.\n\nAny concurrent disease or condition that may interfere with study participation or affect patient safety (e.g., active or uncontrolled infection).\n\nOther invasive malignancies (including second primary breast cancer) that may interfere with study outcomes or compliance.\n\nPrior chemotherapy, endocrine therapy, or biologic therapy for breast cancer (except diagnostic biopsy for primary breast cancer).\n\nMajor surgery within 4 weeks prior to study entry or unresolved significant medical conditions.\n\nTumors that are non-measurable during the study treatment.\n\nAny other condition that, in the investigator's judgment, makes the subject unsuitable for participation."}, 'identificationModule': {'nctId': 'NCT07492394', 'briefTitle': 'Dalpiciclib With or Without Entinostat and Letrozole in HR+/HER2- Early Breast Cancer', 'organization': {'class': 'OTHER', 'fullName': 'Hebei Medical University Fourth Hospital'}, 'officialTitle': 'An Open-Label, Randomized, Phase II Study of Dalpiciclib in Combination With Entinostat and Letrozole Versus Dalpiciclib Plus Letrozole as Neoadjuvant Therapy in Patients With HR-positive, HER2-negative Early Breast Cancer', 'orgStudyIdInfo': {'id': 'OBU-BC-II-278'}}, 'armsInterventionsModule': {'armGroups': [{'type': 'EXPERIMENTAL', 'label': 'Dalpiciclib Plus Letrozole and Entinostat Arm', 'description': 'Dalpiciclib: 125 mg orally once daily on Days 1-21 of each 28-day cycle (3 weeks on, 1 week off), for a total of 6 cycles.\n\nLetrozole: 2.5 mg orally once daily continuously, for a total of 6 cycles. Entinostat: 3 mg orally once weekly on Days 1-28 of each 28-day cycle, for a total of 6 cycles.', 'interventionNames': ['Drug: Dalpiciclib', 'Drug: Letrozole']}, {'type': 'PLACEBO_COMPARATOR', 'label': 'Dalpiciclib Plus Letrozole Arm', 'description': 'Dalpiciclib: 150 mg orally once daily on Days 1-21 of each 28-day cycle (3 weeks on, 1 week off), for a total of 6 cycles.\n\nLetrozole: 2.5 mg orally once daily continuously, for a total of 6 cycles.', 'interventionNames': ['Drug: entinostat', 'Drug: Dalpiciclib', 'Drug: Letrozole']}], 'interventions': [{'name': 'entinostat', 'type': 'DRUG', 'otherNames': ['HDAC inhibitor'], 'description': 'Entinostat is added in the experimental arm, while the control arm does not receive Entinostat.', 'armGroupLabels': ['Dalpiciclib Plus Letrozole Arm']}, {'name': 'Dalpiciclib', 'type': 'DRUG', 'description': 'Dalpiciclib is both added in the experimental arm and control arm.', 'armGroupLabels': ['Dalpiciclib Plus Letrozole Arm', 'Dalpiciclib Plus Letrozole and Entinostat Arm']}, {'name': 'Letrozole', 'type': 'DRUG', 'description': 'Letrozole is both added in the experimental arm and control arm.', 'armGroupLabels': ['Dalpiciclib Plus Letrozole Arm', 'Dalpiciclib Plus Letrozole and Entinostat Arm']}]}, 'contactsLocationsModule': {'locations': [{'zip': '050000', 'city': 'Shijiazhuang', 'state': 'Hebei', 'status': 'RECRUITING', 'country': 'China', 'contacts': [{'name': 'Zhenchuan Song', 'role': 'CONTACT', 'email': 'songzhch@hotmail.com', 'phone': '185 31117857'}], 'facility': 'The Fourth Hospital of Hebei Medical University', 'geoPoint': {'lat': 38.04139, 'lon': 114.47861}}], 'centralContacts': [{'name': 'Zhenchuan Song', 'role': 'CONTACT', 'email': 'songzhch@hotmail.com', 'phone': '18531117857'}], 'overallOfficials': [{'name': 'Zhenchuan Song', 'role': 'STUDY_CHAIR', 'affiliation': 'he Fourth Hospital of Hebei Medical University'}]}, 'ipdSharingStatementModule': {'ipdSharing': 'NO'}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'Hebei Medical University Fourth Hospital', 'class': 'OTHER'}, 'collaborators': [{'name': 'Jiangsu Hengrui Pharmaceutical Co., Ltd.', 'class': 'INDUSTRY'}], 'responsibleParty': {'type': 'SPONSOR'}}}}