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

Plain English Summary

Dalpiciclib With or Without Entinostat and Letrozole in HR+/HER2- Early Breast Cancer is a Phase 2 clinical trial sponsored by Hebei Medical University Fourth Hospital studying Breast Cancer. This study tests two different combinations of drugs to see which is better for treating early-stage breast cancer before surgery. It is for women with hormone-receptor-positive, HER2-negative early breast cancer. Participation involves taking study drugs for about 6 months and having regular check-ups, imaging, and biopsies. Standard treatment options for this type of breast cancer include surgery, radiation, chemotherapy, and hormone therapy. The trial aims to enroll 60 participants.

Official Summary

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. A 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. After 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. Treatment arms: Arm A (30 patients): Dalpiciclib 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 Arm B (30 patients): Dalpiciclib 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. After 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. Tr

Who Can Participate

Here is what you need to know about eligibility for this trial. Women aged 18 to 74 with a confirmed diagnosis of hormone-receptor-positive, HER2-negative early breast cancer. Must not have had prior treatment for breast cancer and have at least one measurable tumor. Cannot join if pregnant, breastfeeding, have metastatic breast cancer, or certain heart or lung conditions. This trial is studying Breast Cancer, so participants generally need a confirmed diagnosis. The trial is currently accepting new participants.

What They're Measuring

The primary outcome measures how many patients achieve a significant reduction in tumor size or disappearance after treatment, indicating the therapy's effectiveness in shrinking the cancer before sur The specific primary outcome measures are: ORR (From baseline to end of neoadjuvant therapy (approximately 6 cycles, ~24 weeks). These endpoints are how researchers determine whether the treatment is effective and will form the basis of any future regulatory submissions.

About This Phase

This trial is in Phase 2, which tests whether the treatment actually works against the target condition. Phase 2 trials involve 100-300 patients and continue to monitor safety while evaluating effectiveness. This phase often tests different dosages to find the optimal amount. About 33% of Phase 2 drugs advance to Phase 3. If successful, the treatment will move to large-scale Phase 3 trials needed for FDA approval.

Why This Trial Matters

This trial aims to find a more effective neoadjuvant (pre-surgery) treatment for early breast cancer, potentially improving outcomes and reducing the need for more aggressive therapies. Phase 2 success would typically lead to larger Phase 3 trials needed for regulatory approval. This research targets Breast Cancer, where improved treatment options are needed.

Investor Insight

This trial explores novel drug combinations for a common cancer type, with potential to capture a significant market share if successful, though approval probability depends on demonstrating superior Phase 2 trials have approximately a 15-20% chance of eventually gaining FDA approval.

Is This Trial Right for Me?

Ask your doctor about the specific drugs being tested, potential side effects, and how this treatment compares to standard options. You will need to attend regular appointments for drug administration, blood tests, imaging scans (ultrasound, MRI), and biopsies. Be prepared for potential side effects and discuss any concerns with your healthcare team promptly. This trial is currently recruiting participants. The trial is being conducted at 1 site. Always discuss clinical trial participation with your healthcare provider before making any decisions. This information is for educational purposes only and is not medical advice.

AI-generated analysis for educational purposes only. This is not medical advice. Discuss clinical trial participation with your doctor. Data sourced from ClinicalTrials.gov.

Study Design

• Study Type: INTERVENTIONAL
• Allocation: NON_RANDOMIZED
• Model: PARALLEL
• Masking: NONE
• Enrollment: 60 participants

Interventions

• DRUG: entinostat — Entinostat is added in the experimental arm, while the control arm does not receive Entinostat.
• DRUG: Dalpiciclib — Dalpiciclib is both added in the experimental arm and control arm.
• DRUG: Letrozole — Letrozole is both added in the experimental arm and control arm.

Primary Outcomes

• ORR (From baseline to end of neoadjuvant therapy (approximately 6 cycles, ~24 weeks)

Secondary Outcomes

• tpCR (At the time of definitive surgery (approximately 18-24 weeks after initiation of neoadjuvant therapy))
• Breast-conserving surgery (BCS) rate (At the time of definitive surgery)
• Proportion of participants achieving PEPI 0 (At the time of definitive surgery)

Full Eligibility Criteria

Inclusion Criteria:

\- Inclusion Criteria

1. Female patients aged ≥18 and \<75 years, including postmenopausal, premenopausal, or perimenopausal. Postmenopause is defined as:Prior bilateral oophorectomy, or age ≥60 years; orAge \<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; orPremenopausal or perimenopausal women willing to receive LHRH agonist (OFS) therapy during the study.
2. Histologically 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).
3. At least one measurable lesion according to RECIST 1.1; clinical stage T1c-T2, cN1-2, or T3-T4, cN0-2.
4. No prior anticancer therapy for breast cancer, including chemotherapy,endocrine therapy, or targeted therapy.
5. Ability to swallow oral medications.
6. Baseline left ventricular ejection fraction (LVEF) ≥50%.
7. Adequate organ function:Hematology (within 1 week):Absolute neutrophil count (ANC) ≥1.5 × 10⁹/L;White blood cell count (WBC) ≥3.0 × 10⁹/L;Platelet count ≥90 × 10⁹/L;Hemoglobin ≥90 g/L Liver and kidney function (within 1 week):Total bilirubin (TBIL) ≤ upper limit of normal (ULN);ALT and AST ≤1.5 × ULNBUN and creatinine ≤1.5 × ULN, with creatinine clearance ≥60 mL/min (Cockcroft-Gault formula)
8. ECG: Corrected QT interval ≤470 ms (12-lead ECG)
9. Willingness and ability to undergo all required biopsy procedures.
10. Women 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.
11. Voluntary participation with signed informed consent, good compliance, and willingness to adhere to follow-up requirements.

Exclusion Criteria:

\- Exclusion Criteria

1. Pregnant or breastfeeding women, or women with a positive pregnancy test at baseline; women of childbearing potential unwilling to use effective contraception during the study.
2. Bilateral breast cancer or inflammatory breast cancer.
3. Stage IV (metastatic) breast cancer at initial diagnosis.
4. History of congestive heart failure, unstable angina, significant arrhythmia, or myocardial infarction.
5. Active pulmonary disease, including interstitial lung disease, pneumonia, pulmonary fibrosis, or other acute lung conditions.
6. Significant liver disease, such as acute or fulminant hepatitis, impaired coagulation factor synthesis, or other severe hepatic dysfunction.
7. For patients positive for HBsAg or HBV core antibody, peripheral blood HBV DNA must be \<1×10³ IU/mL to be eligible.
8. Any concurrent disease or condition that may interfere with study participation or affect patient safety (e.g., active or uncontrolled infection).
9. Other invasive malignancies (including second primary breast cancer) that may interfere with study outcomes or compliance.
10. Prior chemotherapy, endocrine therapy, or biologic therapy for breast cancer (except diagnostic biopsy for primary breast cancer).
11. Major surgery within 4 weeks prior to study entry or unresolved significant medical conditions.
12. Tumors that are non-measurable during the study treatment.
13. Any other condition that, in the investigator's judgment, makes the subject unsuitable for participation.

Trial Locations

• The Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei, China

Frequently Asked Questions

Related Conditions

• Breast Cancer
• Hormone Receptor-Positive Breast Cancer
• HER2-Negative Breast Cancer
• Early Breast Cancer
• Neoadjuvant Therapy
• Endocrine Therapy
• Oncology
• Cancer Research
• Clinical Trials
• Drug Combinations

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