Trial of Neoadjuvant Docetaxel ± Metronomic Capecitabine/CTX Followed by FEC in Women With Operable Triple Negative Breast Cancer

NCT02897050 | Suspended Phase 2 DMC

• 1 other identifier: BCCT2016001
• Study Type: interventional
• Target: 170
• Locations: 1 country
• Sites: 4

Brief Summary

This multi-center, open-label, phase II randomized controlled trial is to evaluate the efficacy of docetaxel(T) combined with metronomic cyclophosphamide/capecitabine (mCX) followed by fluorouracil /epirubicin/cyclophosphamide (FEC) versus T followed by FEC as neoadjuvant chemotherapy in treating women with triple negative breast cancer (TNBC), and to study the anti-tumor immune effect of metronomic neoadjuvant chemotherapy. 186 stage M0 TNBC patients who had a primary tumor \> 2cm by imaging or an axillary lymph node \> 2cm by imaging are randomly enrolled to receive neoadjuvant T combined with mCX (3 cycles) followed by FEC (3 cycles) or T (3cycles) followed by FEC (3 cycles) before surgery. The primary end point is pathological complete response (pCR) rate, and the secondary end points include: clinical response rate, toxicities, breast-conserving rate, Ki67 and CD31 reduction rate, changes in the percentages of peripheral blood or tumor microenvironmental regulatory T cells (Treg), T helper cells (Th), CD8+ T cell, and tumor-specific CTL, and changes in tumor microenvironmental immune cytokines. Once there is a significant statistical difference in terms of pCR rate between two groups, 3-year disease-free survival (DFS) and 3-year overall survival (OS) will be included in the secondary end points. The aims of this study are to determine whether the neoadjuvant T combined with metronomic CX followed by FEC can significantly increase the pCR rate in TNBC with acceptable toxicity, and to explore the anti-tumor immune effect of metronomic neoadjuvant chemotherapy.

Conditions

Breast Cancer

Outcome Measures

Primary Outcomes (1)

• Pathological complete response (pCR) rate

  at definitive surgery (20-24 weeks after the first dose of study medication)

Secondary Outcomes (9)

• Ultrasound response rate

  at definitive surgery (20-24 weeks after the first dose of study medication)

• Breast-conserving surgery rate

  at definitive surgery (20-24 weeks after the first dose of study medication)

• Number of participants with treatment-related adverse events as assessed by CTCAE v4.0

  during on-neoadjuvant therapy period (defined as the period from the first dose of study medication up to 30 days of the last dose)

• Tumor Ki67 reduction rate in relation to neoadjuvant therapy

  at definitive surgery (20-24 weeks after the first dose of study medication)

• Tumor CD31 reduction rate in relation to neoadjuvant therapy

  at definitive surgery (20-24 weeks after the first dose of study medication)

Study Arms (2)

T+mCX followed by FEC

EXPERIMENTAL

Docetaxel 75mg/m2, iv, d1 + CTX 50 mg/d, po, d1-d21 + capecitabine 1200mg/m2/d, po, d1-d21 \* 3 cycles (21 days per cycle) followed by fluorouracil 500mg/m2,iv,d1 + epirubicin 100mg/m2,iv,d1 + cyclophosphamide 500mg/m2,iv,d1 \* 3 cycles (21 days per cycle)

Drug: Docetaxel; Drug: Capecitabine; Drug: Cyclophosphamide (tablet); Drug: Fluorouracil; Drug: Epirubicin; Drug: Cyclophosphamide (injection)

T followed by FEC

ACTIVE COMPARATOR

Docetaxel 100mg/m2, iv, d1 \* 3 cycles (21 days per cycle) followed by fluorouracil 500mg/m2,iv,d1 + epirubicin 100mg/m2,iv,d1 + cyclophosphamide 500mg/m2,iv,d1 \* 3 cycles (21 days per cycle)

Drug: Docetaxel; Drug: Fluorouracil; Drug: Epirubicin; Drug: Cyclophosphamide (injection)

Interventions

Docetaxel DRUG

Docetaxel 75mg/m2, iv, d1 or 100mg/m2, iv, d1

T followed by FEC; T+mCX followed by FEC

Capecitabine DRUG

Capecitabine 1200mg/m2/d, po, d1-d21

Also known as: Xeloda

T+mCX followed by FEC

Cyclophosphamide (tablet) DRUG

Cyclophosphamide 50 mg/d, po, d1-d21

Also known as: CTX

T+mCX followed by FEC

Fluorouracil DRUG

Fluorouracil 500mg/m2, iv, d1

Also known as: 5-Fu

T followed by FEC; T+mCX followed by FEC

Epirubicin DRUG

Epirubicin 100mg/m2, iv, d1

T followed by FEC; T+mCX followed by FEC

Cyclophosphamide (injection) DRUG

Cyclophosphamide 500mg/m2, iv, d1

Also known as: CTX

T followed by FEC; T+mCX followed by FEC

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• The patients signed the written informed consent
• The patients present with non-metastatic unilateral invasive ER-negative (IHC\<10%), PR-negative(IHC\<10%), HER2-negative breast cancer with a primary breast tumor \> 2cm by imaging or an axillary lymph node \> 2cm by imaging.
• years old\< age \< 70 years old.
• The patients have no history of hormone therapy, chemotherapy, breast cancer surgery and radiotherapy.
• The patients have normal cardiac functions by echocardiography.
• The patients' ECOG scores are ≤2.
• The patients can swallow pills.
• The results of patients' blood tests are as follows:
• Hb≥90g/L;
• WBC≥4E+9/L;
• Plt≥100E+9/L;
• Neutrophils≥1.5E+9/L;
• ALT and AST ≤ triple of normal upper limit;
• TBIL ≤ 1.5 times of normal upper limit;
• Creatinine ≤ 1.5 times of normal upper limit.

You may not qualify if:

• The patients have other cancers at the same time or have the history of other cancers except controlled skin basal cell carcinoma or skin squamous cell carcinoma or carcinoma in situ of cervix uterus;
• The patients have active infections that were not suitable for chemotherapy;
• The patients have severe non-cancerous diseases.
• The patients have bilateral breast cancers or male breast cancers or inflammatory breast cancers.
• The patients are undergoing current administration of anti-cancer therapies, or are attending other clinical trials.
• The patients are in some special conditions that they cannot understand the written informed consent, such as they are demented or hawkish.
• The patients have allergic history or contraindication of any of the interventional drugs.

Sponsors & Collaborators

• Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University: lead

Study Sites (4)

Sun Yat-sen Memorial Hospital

Guangzhou, Guangdong, 510120, China

Location

Peking University Shenzhen Hospital

Shenzhen, Guangdong, China

Location

Second Xiangya Hospital of Central South University

Changsha, Hunan, China

Location

Xinjiang Medical School Cancer Hospital

Ürümqi, Xinjiang, 830000, China

Location

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Docetaxel; Capecitabine; Cyclophosphamide; Tablets; Fluorouracil; Epirubicin; Injections

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Uracil; Pyrimidinones; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Phosphoramides; Organophosphorus Compounds; Dosage Forms; Pharmaceutical Preparations; Doxorubicin; Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates; Drug Administration Routes; Drug Therapy; Therapeutics

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: President of Sun Yat-sen Memorial Hospital

Study Record Dates

• First Submitted: September 7, 2016
• First Posted: September 12, 2016
• Study Start: September 1, 2016
• Primary Completion: December 1, 2022
• Study Completion: September 1, 2024
• Last Updated: April 20, 2022

Record last verified: 2022-04

Locations

CN (4)