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The Trial Comparing Dose-dense AC-T With TP as Adjuvant Therapy for TNBC With Homologous Recombination Repair Deficiency

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT03876886
Recruitment Status : Recruiting
First Posted : March 15, 2019
Last Update Posted : March 21, 2019
Information provided by (Responsible Party):
Binghe Xu, Chinese Academy of Medical Sciences

Brief Summary:

The purpose of this trial is to compare the 3-year disease-free survival of dose-dense epirubicin and cyclophosphamide followed by paclitaxel with paclitaxel plus carboplatin as adjuvant therapy for triple-negative breast cancer with homologous recombination repair deficiency.

The other purpose of this trial is to observe the patient's tolerance.

Condition or disease Intervention/treatment Phase
Triple Negative Breast Cancer Drug: Epirubicin Drug: Cyclophosphamide Drug: Paclitaxel Drug: Carboplatin Phase 3

Detailed Description:

Triple-negative breast cancer (TNBC) lack the expression of oestrogen receptor (ER), progesterone receptor(PR) and human epidermal growth factor receptor 2 (HER2) , and characterizes an aggressive behavior with higher risk of recurrence and death compared to other breast cancer subtypes. Little therapeutic progress has been made in adjuvant therapy in TNBC during the past decades and the standard of care is still missing.

Pre-clinical and clinical data suggest that platinum-based regimens represent an emerging therapeutic option for selected patients with homologous recombination repair deficiency (HRD). The HR system is critical in regulating and maintaining genome stability, and is one of the most commonly altered systems in TNBCs, up to 15-20% TNBC patients carry germline BRCA1/2 mutations. Other HR genes included PALB2, RAD51 etc. Tumors that harbor HRD possess an increased burden of genomic aberrations and lesions, and have been shown to have increased sensitivity to DNA crosslinking agents such as platinum salts. Platinum-based regimens have been encouraging in TNBC patients with HRD, given increases in both pathologic complete response (pCR) rates in neoadjuvant trials and objective response rates(ORR) in metastatic diseases. Further information are needed on how platinum-containing therapies affect long-term outcomes in the adjuvant setting.

In this trial, the investigators intend to compare the 3-year disease-free survival (DFS) of dose-dense epirubicin and cyclophosphamide followed by paclitaxel with paclitaxel plus carboplatin as adjuvant therapy in high-risk node-negative or node-positive TNBC patients with HRD. The other purpose of this trial is to observe the participants' tolerance.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 200 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Randomized Phase Ⅲ Trial Comparing Dose-dense Epirubicin and Cyclophosphamide Followed by Paclitaxel With Paclitaxel Plus Carboplatin as Adjuvant Therapy for Triple-negative Breast Cancer With Homologous Recombination Repair Deficiency
Actual Study Start Date : February 22, 2019
Estimated Primary Completion Date : February 2024
Estimated Study Completion Date : December 2024

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
Active Comparator: AC-T(dose-dense)
A: epirubicin, pharmorubicin (EPI) C: cyclophosphamide (CTX) T: paclitaxel (PTX)
Drug: Epirubicin
Epirubicin 90mg/m2 iv d1 or divide into two days

Drug: Cyclophosphamide
cyclophosphamide600mg/m2 iv d1,q14d*4cycles;with G-CSF support: 3ug/kg ih

Drug: Paclitaxel
paclitaxel 175mg/m2 iv d1, q14d*4cycles

Experimental: TP(dose-dense)
T: paclitaxel (PTX) P: carboplatin (CBP)
Drug: Carboplatin
carboplatin AUC=3 iv d2, q14d*8cycles;with G-CSF support: 3ug/kg ih

Drug: Paclitaxel
paclitaxel 175mg/m2 iv d1, q14d*8cycles

Primary Outcome Measures :
  1. 3-year disease-free survival [ Time Frame: Three years ]
    The participants will be followed by the telephone for the duration, an expected average of 3 years.

Secondary Outcome Measures :
  1. Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability] [ Time Frame: Three years ]
    Incidence of neutropenic fever; Incidence of grade 3-4 side effects; Toxicity assessed by NCI CTCAE v5.0

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 60 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  1. 18-60 years
  2. Histologically confirmed adenocarcinoma of the breast, complete tumor removal by either modified radical mastectomy or local excision plus axillary lymph node dissection (i.e., breast conservation therapy) or sentinel node biopsy. (Tumor-free margins at least 1 mm for both invasive and noninvasive carcinoma except for lobular carcinoma in situ (less than 1 mm allowed);
  3. Histologically confirmed ER(-) PR(-) and HER-2(IHC(immunohistochemistry) 0-1+ or FISH (fluorescence in situ hybridization) negative)
  4. Next-generation sequencing confirmed homologous recombination repair deficiency
  5. Meet one of the following criteria:

(1) Positive axillary lymph nodes; (2) Negative axillary lymph nodes with at least one of the following risk factors: age<= 35 years; grade III; infiltrative tumor size > 2cm; intravascular tumor embolus; Ki-67>=50%.

6. Eastern Cooperative Oncology Group (ECOG) Performance Score 0-1 7. Adequate bone marrow reserve with ANC > 1500, HGB > 9g/dL and platelets > 100,000.

8. Adequate renal function with serum creatinine < 2.0. 9. Adequate hepatic reserve with serum bilirubin < 2.0, AST/ALT < 2X the upper limit of normal, and alkaline phosphatase < 5X the upper limit of normal. Serum bilirubin > 2.0 is acceptable in the setting of known Gilbert's syndrome.

10. Not pregnant, and on appropriate birth control if of child-bearing potential.

11. Written informed consent according to the local ethics committee requirements.

Exclusion Criteria:

  1. Prior systemic treatment of breast cancer, including chemotherapy;
  2. Metastatic breast cancer;
  3. Patients with medical conditions that indicate intolerant to adjuvant therapy and related treatment, including uncontrolled pulmonary disease, diabetes mellitus, severe infection, active peptic ulcer, coagulation disorder, connective tissue disease or myelo-suppressive disease;
  4. Has active hepatitis B or hepatitis C with abnormal liver function tests (LFTs) or is known to be HIV positive;
  5. Contraindication for using dexamethasone;
  6. History of congestive heart failure, uncontrolled or symptomatic angina pectoris, arrhythmia or myocardial infarction; poorly controlled hypertension (systolic BP>180 mmHg or diastolic BP>100 mmHg);
  7. Pregnant or breast feeding.
  8. Hepatic, renal, or bone marrow dysfunction as detailed above.
  9. Known severe hypersensitivity to any drugs in this study;
  10. Treatment with any investigational drugs within 30 days before the beginning of study treatment.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT03876886

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Contact: Binghe Xu +86-10-87788120
Contact: Qing Li +86-10-87788120

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China, Beijing
National Cancer Center, Cancer Hospital/Chinese Academy of Medical Sciences and Peking Union Medical College Recruiting
Beijing, Beijing, China, 100021
Contact: Binghe XU, M.D.    86-10-88788826   
Sponsors and Collaborators
Chinese Academy of Medical Sciences

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Responsible Party: Binghe Xu, Professor of Medical Oncology, Chinese Academy of Medical Sciences Identifier: NCT03876886     History of Changes
Other Study ID Numbers: BXu-1839
First Posted: March 15, 2019    Key Record Dates
Last Update Posted: March 21, 2019
Last Verified: March 2019

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No

Keywords provided by Binghe Xu, Chinese Academy of Medical Sciences:
homologous recombination deficiency;adjuvant chemotherapy;anthracycline;taxanes;platinum

Additional relevant MeSH terms:
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Breast Neoplasms
Triple Negative Breast Neoplasms
Neoplasms by Site
Breast Diseases
Skin Diseases
Albumin-Bound Paclitaxel
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Myeloablative Agonists
Antibiotics, Antineoplastic
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors