CDK4/6 Inhibitors Intensification for Chemotherapy Omission in Small Size High-risk ER-positive Breast Cancer（Cinnamon）

Plain English Summary

CDK4/6 Inhibitors Intensification for Chemotherapy Omission in Small Size High-risk ER-positive Breast Cancer（Cinnamon） is a Phase 3 clinical trial sponsored by Fudan University studying Breast Cancer. This trial tests if a new treatment approach without chemotherapy can be as effective as standard chemotherapy for certain early breast cancer patients. It is for women aged 18-70 with small (up to 2cm), hormone-driven (ER-positive), HER2-negative breast cancer that has high-risk features suggesting it might return. Participation involves receiving either the new treatment (a drug called Dalpiciclib with hormone therapy) or standard chemotherapy followed by hormone therapy, with regular follow-ups. The alternative is the current standard of care, which usually involves chemotherapy followed by hormone therapy. The trial aims to enroll 2288 participants.

Official Summary

This study is a Phase III non-inferiority trial targeting a specific subset of early breast cancer patients: those with HR-positive/HER2-negative, node-negative small tumors (typically ≤2cm) but who exhibit high-risk features for recurrence (such as high histological grade, high Ki-67 index, etc.). Currently, the standard adjuvant treatment for these patients often includes chemotherapy followed by endocrine therapy, despite their small tumor size, due to the high-risk biological characteristics. However, chemotherapy can bring significant toxicity and long-term side effects. This trial explores whether a chemotherapy-sparing approach is feasible. It compares the efficacy and safety of using the CDK4/6 inhibitor Dalpiciclib combined with endocrine therapy (AI ± OFS) directly, without chemotherapy, against the traditional approach of chemotherapy (TC regimen) followed by endocrine therapy. The primary goal is to demonstrate that the chemotherapy-free regimen is not inferior to the chemotherapy-containing regimen in terms of 5-year invasive disease-free survival (iDFS). If successful, this study could potentially de-escalate treatment for this high-risk population, sparing them from chemotherapy-related toxicities while maintaining excellent oncological outcomes.

Who Can Participate

Here is what you need to know about eligibility for this trial. Women aged 18 to 70 with a specific type of early breast cancer (ER-positive, HER2-negative, small tumor size up to 2cm). Patients must have at least one high-risk feature, such as a high Ki-67 index, Grade 3 tumor, or a high score on genetic tests indicating a higher risk of recurrence. Individuals who have already received any cancer treatment before this study, have bilateral breast cancer, or have evidence of cancer spread to other parts of the body cannot join. Good general health is required, with specific limits on blood counts, liver, and kidney function, and no severe heart or other major organ problems. This trial is studying Breast Cancer, so participants generally need a confirmed diagnosis.

What They're Measuring

The main goal is to see if the new treatment is just as good as standard chemotherapy at preventing the cancer from returning within 5 years. The specific primary outcome measures are: iDFS (5 years). 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 3, the final and most rigorous stage before seeking FDA approval. Phase 3 trials involve 300-3,000+ patients across multiple sites and compare the new treatment directly against the current standard of care. These pivotal trials generate the evidence needed for regulatory review. About 58% of Phase 3 drugs receive FDA approval. Successful Phase 3 results typically lead to a New Drug Application submission.

Why This Trial Matters

This trial aims to find a way to avoid chemotherapy for certain high-risk early breast cancer patients, potentially reducing side effects while maintaining cancer control. As a Phase 3 trial, positive results could directly lead to FDA approval, making this treatment available to the broader patient population. This research targets Breast Cancer, where improved treatment options are needed.

Investor Insight

This trial addresses a significant unmet need in early breast cancer treatment, potentially expanding the use of targeted therapies and reducing chemotherapy burden for a large patient population. Phase 3 trials have approximately a 50-60% chance of gaining FDA approval if they reach this stage. The large enrollment target of 2288 participants suggests significant investment in this program.

Is This Trial Right for Me?

Ask your doctor if your tumor has high-risk features and if you might be eligible for this trial. Be prepared for regular clinic visits for treatment, tests, and monitoring for up to 5 years. Understand that you will be randomly assigned to one of the two treatment groups. The trial is being conducted at multiple sites. 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: RANDOMIZED
• Model: PARALLEL
• Masking: NONE
• Enrollment: 2,288 participants

Interventions

• DRUG: Dalpiciclib+AI ± OFS — Chemotherapy-free regimen Dalpiciclib 125mg qd d1-d21 Q4W orally for 2 years Combined with AI (at least 5 years) ± OFS
• DRUG: TC (Docetaxel + Cyclophosphamide) × 4 cycles- endocrine therapy — TC (Docetaxel + Cyclophosphamide) × 4 cycles Endocrine therapy according to current indications and physician's choice

Primary Outcomes

• iDFS (5 years)

Secondary Outcomes

• DFS (5 years)
• DDFS (5 years)
• RFS (5 years)
• OS (5 years)
• Safety and Tolerability (5 years)

Full Eligibility Criteria

Inclusion Criteria:

1. Female, aged 18 to 70 years.
2. Histologically confirmed early breast cancer with pathological stage T1N0, 0.5 cm \< tumor size ≤ 2 cm, ER-positive/HER2-negative, with ER expression ≥ 50%; and willingness to receive adjuvant dalpiciclib treatment.
3. Presence of at least one of the following high-risk features:

   Ki-67 index ≥ 50%; Grade 3 (G3) tumor; an indication for chemotherapy based on results from multigene assays, including the 21-gene recurrence score and the 70-gene signature ; Age ≤ 40 years.
4. ECOG performance status: 0 to 1.
5. Adequate organ function, defined as meeting the following criteria:

   Hematology (no blood transfusion within 14 days): Hemoglobin (HB) ≥ 90 g/L; Absolute Neutrophil Count (ANC) ≥ 1.5 × 10⁹/L; Platelet (PLT) ≥ 100 × 10⁹/L.

   Biochemistry: Total Bilirubin (TBIL) ≤ 1.5 × Upper Limit of Normal (ULN); Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) ≤ 3 × ULN; Serum Creatinine (Cr) ≤ 1 × ULN, with creatinine clearance \> 50 mL/min (calculated using the Cockcroft-Gault formula).
6. Voluntary participation with written informed consent, good compliance, and willingness to comply with follow-up requirements.

Exclusion Criteria:

1. Patients who have received neoadjuvant therapy, including chemotherapy, targeted therapy, radiotherapy, or endocrine therapy.
2. Bilateral breast cancer.
3. History of other prior malignancies, except for curatively treated basal cell carcinoma of the skin and carcinoma in situ of the cervix.

4\) Evidence of metastasis at any site. 5) Any T4 lesion (UICC 1987), including skin involvement, tumor fixation/mass, or inflammatory breast cancer.

6\) Pregnant or lactating women, or women of childbearing potential who are unwilling to use adequate contraception.

7\) Concurrent participation in another clinical trial. 8) Severe organ dysfunction (cardiac, pulmonary, hepatic, or renal). Left Ventricular Ejection Fraction (LVEF) \< 50% (by echocardiography). History of severe cardiovascular or cerebrovascular disease within 6 months prior to randomization (e.g., unstable angina, chronic heart failure, uncontrolled hypertension \>150/90 mmHg, myocardial infarction, or cerebrovascular accident). Patients with poorly controlled diabetes mellitus or severe hypertension.

9\) Known hypersensitivity to taxanes or their excipients. 10)Severe or uncontrolled infection. 11)History of psychoactive substance abuse that cannot be discontinued, or history of mental disorders.

12)Patients deemed by the investigator to be unsuitable for participation in this study.

13)Patient refusal to receive adjuvant dalpiciclib treatment.

Frequently Asked Questions

Related Conditions

• Breast Cancer
• ER-positive Breast Cancer
• HER2-negative Breast Cancer
• Early Breast Cancer
• High-risk Breast Cancer
• Hormone Receptor-positive Breast Cancer
• Adjuvant Therapy
• Oncology
• Medical Oncology
• Cancer Treatment

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