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

Primary Purpose

Triple Negative Breast Cancer

Status
Recruiting
Phase
Phase 3
Locations
China
Study Type
Interventional
Intervention
Epirubicin
Cyclophosphamide
Paclitaxel
Carboplatin
Paclitaxel
Sponsored by
Chinese Academy of Medical Sciences
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Triple Negative Breast Cancer focused on measuring homologous recombination deficiency;adjuvant chemotherapy;anthracycline;taxanes;platinum

Eligibility Criteria

18 Years - 60 Years (Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • National Cancer Center, Cancer Hospital/Chinese Academy of Medical Sciences and Peking Union Medical CollegeRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Experimental

Arm Label

AC-T(dose-dense)

TP(dose-dense)

Arm Description

A: epirubicin, pharmorubicin (EPI) C: cyclophosphamide (CTX） T: paclitaxel (PTX）

T: paclitaxel (PTX） P: carboplatin (CBP)

Outcomes

Primary Outcome Measures

3-year disease-free survival
The participants will be followed by the telephone for the duration, an expected average of 3 years.

Secondary Outcome Measures

Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]
Incidence of neutropenic fever; Incidence of grade 3-4 side effects; Toxicity assessed by NCI CTCAE v5.0

Full Information

First Posted
March 14, 2019
Last Updated
March 20, 2019
Sponsor
Chinese Academy of Medical Sciences
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1. Study Identification

Unique Protocol Identification Number
NCT03876886
Brief Title
The Trial Comparing Dose-dense AC-T With TP as Adjuvant Therapy for TNBC With Homologous Recombination Repair Deficiency
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
Study Type
Interventional

2. Study Status

Record Verification Date
March 2019
Overall Recruitment Status
Recruiting
Study Start Date
February 22, 2019 (Actual)
Primary Completion Date
February 2024 (Anticipated)
Study Completion Date
December 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Chinese Academy of Medical Sciences

4. Oversight

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

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Triple Negative Breast Cancer
Keywords
homologous recombination deficiency;adjuvant chemotherapy;anthracycline;taxanes;platinum

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
200 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
AC-T(dose-dense)
Arm Type
Active Comparator
Arm Description
A: epirubicin, pharmorubicin (EPI) C: cyclophosphamide (CTX） T: paclitaxel (PTX）
Arm Title
TP(dose-dense)
Arm Type
Experimental
Arm Description
T: paclitaxel (PTX） P: carboplatin (CBP)
Intervention Type
Drug
Intervention Name(s)
Epirubicin
Intervention Description
Epirubicin 90mg/m2 iv d1 or divide into two days
Intervention Type
Drug
Intervention Name(s)
Cyclophosphamide
Intervention Description
cyclophosphamide600mg/m2 iv d1,q14d*4cycles;with G-CSF support: 3ug/kg ih
Intervention Type
Drug
Intervention Name(s)
Paclitaxel
Intervention Description
paclitaxel 175mg/m2 iv d1, q14d*4cycles
Intervention Type
Drug
Intervention Name(s)
Carboplatin
Intervention Description
carboplatin AUC=3 iv d2, q14d*8cycles;with G-CSF support: 3ug/kg ih
Intervention Type
Drug
Intervention Name(s)
Paclitaxel
Intervention Description
paclitaxel 175mg/m2 iv d1, q14d*8cycles
Primary Outcome Measure Information:
Title
3-year disease-free survival
Description
The participants will be followed by the telephone for the duration, an expected average of 3 years.
Time Frame
Three years
Secondary Outcome Measure Information:
Title
Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]
Description
Incidence of neutropenic fever; Incidence of grade 3-4 side effects; Toxicity assessed by NCI CTCAE v5.0
Time Frame
Three years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
60 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: 18-60 years 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); Histologically confirmed ER(-) PR(-) and HER-2(IHC(immunohistochemistry) 0-1+ or FISH (fluorescence in situ hybridization) negative) Next-generation sequencing confirmed homologous recombination repair deficiency 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: Prior systemic treatment of breast cancer, including chemotherapy; Metastatic breast cancer; 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; Has active hepatitis B or hepatitis C with abnormal liver function tests (LFTs) or is known to be HIV positive; Contraindication for using dexamethasone; 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); Pregnant or breast feeding. Hepatic, renal, or bone marrow dysfunction as detailed above. Known severe hypersensitivity to any drugs in this study; Treatment with any investigational drugs within 30 days before the beginning of study treatment.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Binghe Xu
Phone
+86-10-87788120
Email
xubinghe@medmail.com.cn
First Name & Middle Initial & Last Name or Official Title & Degree
Qing Li
Phone
+86-10-87788120
Email
cheryliqing@hotmail.com
Facility Information:
Facility Name
National Cancer Center, Cancer Hospital/Chinese Academy of Medical Sciences and Peking Union Medical College
City
Beijing
State/Province
Beijing
ZIP/Postal Code
100021
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Binghe XU, M.D.
Phone
86-10-88788826
Email
xubinghe@medmail.com.cn

12. IPD Sharing Statement

Learn more about this trial

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

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