Working...
ClinicalTrials.gov
ClinicalTrials.gov Menu

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.
ClinicalTrials.gov Identifier: NCT03876886
Recruitment Status : Recruiting
First Posted : March 15, 2019
Last Update Posted : March 21, 2019
Sponsor:
Information provided by (Responsible Party):
Binghe Xu, Chinese Academy of Medical Sciences

Tracking Information
First Submitted Date  ICMJE March 14, 2019
First Posted Date  ICMJE March 15, 2019
Last Update Posted Date March 21, 2019
Actual Study Start Date  ICMJE February 22, 2019
Estimated Primary Completion Date February 2024   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: March 14, 2019)
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.
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT03876886 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: March 20, 2019)
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
Original Secondary Outcome Measures  ICMJE
 (submitted: March 14, 2019)
Patients' tolerance [ Time Frame: Three years ]
Toxicity as assessed by NCI CTCAE v5.0
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE The Trial Comparing Dose-dense AC-T With TP as Adjuvant Therapy for TNBC With Homologous Recombination Repair Deficiency
Official Title  ICMJE 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
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.

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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Triple Negative Breast Cancer
Intervention  ICMJE
  • 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
  • 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
Study Arms  ICMJE
  • Active Comparator: AC-T(dose-dense)
    A: epirubicin, pharmorubicin (EPI) C: cyclophosphamide (CTX) T: paclitaxel (PTX)
    Interventions:
    • Drug: Epirubicin
    • Drug: Cyclophosphamide
    • Drug: Paclitaxel
  • Experimental: TP(dose-dense)
    T: paclitaxel (PTX) P: carboplatin (CBP)
    Interventions:
    • Drug: Carboplatin
    • Drug: Paclitaxel
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: March 14, 2019)
200
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE December 2024
Estimated Primary Completion Date February 2024   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 60 Years   (Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Binghe Xu +86-10-87788120 xubinghe@medmail.com.cn
Contact: Qing Li +86-10-87788120 cheryliqing@hotmail.com
Listed Location Countries  ICMJE China
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03876886
Other Study ID Numbers  ICMJE BXu-1839
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product
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
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Binghe Xu, Chinese Academy of Medical Sciences
Study Sponsor  ICMJE Chinese Academy of Medical Sciences
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account Chinese Academy of Medical Sciences
Verification Date March 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP