TA(E)C-GP Versus A(E)C-T for the High Risk TNBC Patients and Validation of the mRNA-lncRNA Signature

Efficacy and Safety Study of TA(E)C-GP Versus A(E)C-T for the High Risk Triple-negative Breast Cancer Patients Predicted by the Messenger RNA (mRNA)-Long Non-coding RNA (lncRNA) Signature and Validation of the Signature's Efficacy

The purpose of this study is to compare the efficacy and safety between docetaxel combined with doxorubicin (epirubicin) and cyclophosphamide followed by gemcitabine combined with cisplatin and doxorubicin (epirubicin) combined with cyclophosphamide followed by docetaxel for high risk triple negative breast cancer predicted by the mRNA-lncRNA integrated signature and validation the efficacy of the signature.

Study Overview

• Status: Active, not recruiting
• Conditions: Breast Cancer; Triple Negative Breast Cancer
• Intervention / Treatment: Drug: cyclophosphamide; Drug: docetaxel; Drug: cisplatin; Drug: gemcitabine; Drug: doxorubicin or epirubicin

Detailed Description

Triple-negative breast cancer (TNBC) is one of the most aggressive subtypes of breast cancer. Chemotherapy is the current mainstay of treatment. The treatment of patients with TNBC has been challenging due to the heterogeneity of the disease and the absence of well-defined molecular targets. The investigators' previous study has successfully identified and independently validated prognostic and predictive RNA signatures for TNBC, which could be used to classify TNBC patients into high- or low-risk of recurrence. This study is intended to further validate the efficacy of the mRNA-lncRNA signature and also explore better chemotherapy for the predicted high risk TNBC patients.

The current study is designed to validation the efficacy of the mRNA-lncRNA signature and evaluate the efficacy and safety between docetaxel combined with doxorubicin (epirubicin) and cyclophosphamide followed by gemcitabine combined with cisplatin and doxorubicin (epirubicin) combined with cyclophosphamide followed by docetaxel for high risk triple negative breast cancer predicted by the integrated signature.

Primary endpoint for the study: recurrence free survival; second endpoint for the study: safety, disease free survival and overall survival; This open multi-center prospective randomized control study includes TNBC patients with invasive ductal carcinoma. All eligible patients' tumor samples were tested using real-time polymerase chain reaction (PCR) and recurrence risks were predicted using the mRNA-lncRNA signature. Patients with high recurrence risk were randomized to Group A or Group B to receive respective chemotherapy. Among which Group A: TA(E)C x 4 cycles to GP x 4 cycles (docetaxel + doxorubicin (epirubicin) + cyclophosphamide to gemcitabine + cisplatin), docetaxel: 75 mg/m2 IV on day 1; doxorubicin: 50 mg/m2 IV on day 1 or epirubicin 75 mg/m2 IV on day 1; cyclophosphamide: 500 mg/m2 IV on day 1; gemcitabine: 1250 mg/m2 IV on day 1 and 8; cisplatin: 75 mg/m2 IV on day 1, dosing interval is 21 days. Group B: A(E)C x 4 cycles to T x 4 cycles (doxorubicin (epirubicin) + cyclophosphamide to docetaxel), doxorubicin: 60 mg/m2 IV on day 1 or epirubicin 90 mg/m2 IV on day 1; cyclophosphamide: 600 mg/m2 IV on day 1; docetaxel: 100 mg/m2 IV on day 1, dosing interval is 21 days. Patients with low recurrence risk received chemotherapy in Group C: A(E)C x 4 cycles to T x 4 cycles (doxorubicin (epirubicin) + cyclophosphamide to docetaxel), doxorubicin: 60 mg/m2 IV on day 1 or epirubicin 90 mg/m2 IV on day 1; cyclophosphamide: 600 mg/m2 IV on day 1; docetaxel: 100 mg/m2 IV on day 1, dosing interval is 21 days.

• Study Type: Interventional
• Enrollment (Estimated): 503
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• China
  • Shanghai
    • Shanghai, Shanghai, China, 200032
      • Fudan University Shanghai Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 61 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Age: 18-70 years old
2. Expected survival > 12 months
3. Baseline Eastern Cooperative Oncology Group Performance Status rating 0-1
4. Naïve to chemotherapy or hormonal treatments
5. Pathology confirmed invasive ductal carcinoma of breast
6. Triple negative breast cancer confirmed by pathology
7. No concurrent malignancy (except controlled cervical carcinoma in situ or basal cell carcinoma of skin)
8. No advanced metastasis or metastasis involving brain or liver
9. Adequate bone marrow function, blood routine examination shows neutrophil count ≥ 1.5x109/L, hemoglobin level ≥ 100 g/L, Platelets ≥ 100 x 109/L
10. Adequate liver and kidney function, serum aminotransferase (AST) ≤ 60 Unit/L, serum total bilirubin ≤ 2.5 times Upper Limit of Normal, serum creatinine ≤110μmol/L, urea nitrogen ≤7.1mmol/L
11. No coagulation abnormality
12. Normal heart function, with normal ECG and left ventricular ejection fraction ≥ 55%
13. Women of childbearing age agree to take reliable contraceptive measures during clinical trials, and negative serum or urine pregnancy test within 7 days prior to administration
14. No coagulation abnormality
15. Sign the informed consent statement and voluntarily receive follow-ups, treatments, laboratory tests and other research procedures according to protocol.

Exclusion Criteria:

1. Previous regional or systemic treatment for breast cancer (include but not limited to chemotherapy, radiotherapy, targeted therapy, other clinical trials)
2. Inflammatory breast cancer, bilateral breast cancer or breast cancer already with distant metastasis
3. Complicated with uncontrolled lung disease, severe infection, active peptic ulcer, blood clotting disorders, severe uncontrolled diabetes, connective tissue disorders or bone marrow suppression, and intolerance to neoadjuvant therapy or related treatment
4. Peripheral neuropathy >1 degree caused by any reason
5. History of congestive heart failure, uncontrolled or symptomatic angina, arrhythmias or history of myocardial infarction, refractory hypertension (systolic blood pressure > 180 mmHg or diastolic blood pressure > 100 mmHg);
6. Breast cancer during lactation or pregnancy
7. Mental illness or incompliance to treatment caused by other reasons
8. Known history of severe hypersusceptibility to any agents used in the treatment protocol
9. Patients received major surgery or suffered from severe trauma within 2 months of first administration
10. Currently enroll or recently used (30 days within enrollment) other agent under research or involved in other trial
11. Known to be infected with human immunodeficiency virus (HIV)
12. Other circumstances considered to be inappropriate to be enrolled by researchers

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: High risk group A; TA(E)C x 4 cycles to GP x 4 cycles (docetaxel + doxorubicin (epirubicin) + cyclophosphamide to gemcitabine + cisplatin), docetaxel: 75 mg/m2 IV on day 1; doxorubicin: 50 mg/m2 IV on day 1 or epirubicin 75 mg/m2 IV on day 1; cyclophosphamide: 500 mg/m2 IV on day 1; gemcitabine: 1250 mg/m2 IV on day 1 and 8; cisplatin: 75 mg/m2 IV on day 1, dosing interval is 21 days.	Drug: cyclophosphamide; Drug: docetaxel; Drug: cisplatin; Drug: gemcitabine; Drug: doxorubicin or epirubicin
Active Comparator: High risk group B; A(E)C x 4 cycles to T x 4 cycles (doxorubicin (epirubicin) + cyclophosphamide to docetaxel), doxorubicin: 60 mg/m2 IV on day 1 or epirubicin 90 mg/m2 IV on day 1; cyclophosphamide: 600 mg/m2 IV on day 1; docetaxel: 100 mg/m2 IV on day 1, dosing interval is 21 days.	Drug: cyclophosphamide; Drug: docetaxel; Drug: doxorubicin or epirubicin
Other: Low risk group C; A(E)C x 4 cycles to T x 4 cycles (doxorubicin (epirubicin) + cyclophosphamide to docetaxel), doxorubicin: 60 mg/m2 IV on day 1 or epirubicin 90 mg/m2 IV on day 1; cyclophosphamide: 600 mg/m2 IV on day 1; docetaxel: 100 mg/m2 IV on day 1, dosing interval is 21 days.	Drug: cyclophosphamide; Drug: docetaxel; Drug: doxorubicin or epirubicin

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Disease free survival	three years

Secondary Outcome Measures

Outcome Measure	Time Frame
Recurrence free survival	three years
Number of participants with treatment-related adverse events as assessed by CTCAE v4.0	three years
Overall survival	three years

Collaborators and Investigators

• Sponsor: Fudan University

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2016
• Primary Completion (Actual): December 1, 2023
• Study Completion (Estimated): December 1, 2027

Study Registration Dates

• First Submitted: December 22, 2015
• First Submitted That Met QC Criteria: December 24, 2015
• First Posted (Estimated): December 30, 2015

Study Record Updates

• Last Update Posted (Actual): January 25, 2024
• Last Update Submitted That Met QC Criteria: January 24, 2024
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Keywords: chemotherapy; high risk; triple negative breast cancer; mRNA-lncRNA signature
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; Triple Negative Breast Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antirheumatic Agents; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Alkylating; Alkylating Agents; Myeloablative Agonists; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Antibiotics, Antineoplastic; Docetaxel; Cyclophosphamide; Epirubicin; Doxorubicin; Gemcitabine
• Other Study ID Numbers: 1506147-4