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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.

Phase 3
18 Years
65 Years
Open (Enrolling)
Breast Cancer

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Trial Information

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.

Breast cancer are heterogeneous group of tumors with diverse behavior, outcome, and
sensitivity to therapy.In recent years, the term triple negative (TN) breast cancer has
emerged to describe those cancers which do not express oestrogen (ER) , progesterone (PR)
receptors, or Her2. Many studies had estimated that TN cases represents between 12%-20% of
all breast cancers. Those TN case constitute one of the most challenging breast cancer
groups, with only systemic chemotherapy is currently available for their treatment.

BRCA1 protein normally functions as a negative regulator of the cell cycle, also,
BRCA1-positive tumors encompass a heterogeneous group of tumors that show distinctive
pathological and clinical features. BRCA1-associated cancers are typically high-grade
invasive duct carcinoma and are mostly triple negative.The phenotypic and molecular
similarity of the TNBCs to BRCA1-associated BCs might be of use in designing their treatment
protocol. There is increasing evidence that the DNA repair defects that are characteristic
of BRCA-1 related cancers may provide sensitivity to certain systemic agents to treat TNBC
patients such as the bifunctional alkylating agents and platinum drugs.

Dose density refers to the administration of drugs with a shortened intertreatment interval.
It is based on the observation that in experimental models, a given dose always kills a
certain fraction, rather than a certain number, of exponentially growing cancer cells.
Because human cancers in general, and breast cancers in particular, usually grow by
nonexponential Gompertzian kinetics, this model has been extended to those situations.
Regrowth of cancer cells between cycles of cytoreduction is more rapid in volume-reduced
Gompertzian cancer models than in exponential models. Hence it has been hypothesized that
the more frequent administration of cytotoxic therapy would be a more effective way of
minimizing residual tumor burden than dose escalation. In the INT C9741 trial, the
dose-dense schedule is accomplished by using granulocyte colony-stimulating factor
(filgrastim) to permit every-2-week recycling of the drugs A, T and C at their optimal dose
levels rather than at the conventional 3-week intervals.Sequential therapy refers to the
application of treatments one at a time rather than concurrently. It does not challenge the
concept that multiple drugs are needed to maximally perturb cancers that are composed of
cells heterogeneous in drug sensitivity. Rather, it hypothesizes that for slow-growing
cancers like most breast cancers, it is more important to preserve dose density than to
force a combination, especially if that combination would be more toxic and requires
dose-reductions or delays in drug administration. If dose density is the same in a
sequential combination chemotherapy regimen and a concurrent combination regimen,
theoretical considerations indicate that the therapeutic result should be the same, even if
the sequential pattern happens to be less toxic.

In our trial, we want to compare the 3 years DFS of dose-dense epirubicin and
cyclophosphamide followed by paclitaxel with paclitaxel plus carboplatin as adjuvant therapy
for triple-negative breast cancer.The other purpose of this trial is to observe the
patient's tolerance.

Inclusion Criteria:

1. Patient must accept the modified radical mastectomy

2. Patients with histologically confirmed ER(-) PR(-) and HER-2(-)

3. Positive axillary lymph nodes;negative axillary lymph node with age< 35 years or Ⅲ
grade or intravascular cancer embolus.

4. Age between 18 years to 65 years

5. Able to give informed consent

6. Patients with an Eastern Cooperative Oncology Group (ECOG) performance score of 0 or

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

8. Adequate bone marrow reserve with ANC > 1000 and platelets > 100,000.

9. Adequate renal function with serum creatinine < 2.0.

10. 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.

11. No active major medical or psychosocial problems that could be complicated by study

Exclusion Criteria:

1. received neo-adjuvant therapy

2. Cardiac dysfunction documented by an ejection fraction less than the lower limit of
the facility normal by multi-gated acquisition (MUGA) scan, or 45% by echocardiogram.
-The rate of Disease recurrence

3. Uncontrolled medical problems.

4. Evidence of active acute or chronic infection.

5. Pregnant or breast feeding.

6. Hepatic, renal, or bone marrow dysfunction as detailed above.

Type of Study:


Study Design:

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

3 years DFS

Outcome Description:

the participants will be followed by the telephone for the duration, an expected average of 3 years.

Outcome Time Frame:

3 years

Safety Issue:


Principal Investigator

qing li, bachelor

Investigator Role:

Study Chair

Investigator Affiliation:

Cancer Institute and Hospital, Chinese Academy of Medical Sciences


China: Ethics Committee

Study ID:




Start Date:

May 2011

Completion Date:

June 2013

Related Keywords:

  • Breast Cancer
  • triple-negative breast cancer
  • dose-dense
  • epirubicin and cyclophosphamide followed by paclitaxel(AC-T)
  • paclitaxel plus carboplatin(PC)
  • 3 years DFS
  • the tolerance
  • Breast Neoplasms