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Risk and Clinical Benefit of Chemotherapy and Intensive Endocrine Therapy for Luminal B1 Early-stage Breast Cancer

NCT03373708

Description:

Breast cancer is the most common female malignancy in the world, and the leading cause of cancer-associated mortalities among women. Hormone receptors (HR) including ER and PR are the main prognostic factor for breast cancer patients. Breast cancer subtype was defined by ER, PR, HER2 and Ki67 status since the definition of intrinsic subtypes for breast cancer. Breast cancer which ER are positive have less aggressive and better long-term prognoses than other breast cancer subtype. Luminal B1 was definited as ER Positive, PR positive <20%, or Ki-67 ≥20% , and HER2-Negative. Although standard therapy to HR positive breast cancer is endocrine treatment, evidence reported that Luminal B1 breast cancers with lower PR expression are less sensitive to tamoxifen than luminal A breast cancers with higher PR expression, and the specific mechanism is not clear. We previously had a clinically analysed, and we found the Luminal B1 breast cancer had a significant proportion with 38%. Whether we need standard chemotherapy or chemotherapy based intensive endocrine therapy for those patients? In our research, we divided the patients with ER positive, PR negative, and HER-2 negative into two groups. One groups will be treated with 8 cycles of chemotherapy (EC×4-T×4). The other received 4 cycles of chemotherapy (TC×4) then will be given the intensive endocrine therapy (Goserelin acetate+Tamoxifen for young patients/Letrozole for postmenopausal patients). The primary endpoint is to assess disease-free survival (DFS) and overall survival (OS) in different regiments, the secondary endpoint is to assess the expression of female hormone levels. The correlation of the expression of female hormone levels with the clinical outcomes, so that the investigators could optimize adjuvant treatment regiment with luminal B1 breast cancer.

Related Conditions:
  • Breast Carcinoma
Recruiting Status:

Not yet recruiting

Phase:

Phase 2/Phase 3

Trial Eligibility

Document

Title

  • Brief Title: Risk and Clinical Benefit of Chemotherapy and Intensive Endocrine Therapy for Luminal B1 Early-stage Breast Cancer
  • Official Title: Prospective Randomized Controlled Study on the Risk and Clinical Benefit of Chemotherapy and Intensive Endocrine Therapy for Luminal B1 Early-stage Breast Cancer

Clinical Trial IDs

  • ORG STUDY ID: ShandongCHI-03
  • NCT ID: NCT03373708

Conditions

  • Breast Cancer
  • Chemotherapy
  • Endocrine Breast Diseases

Interventions

DrugSynonymsArms
EpirubicinAdriacinEC follow T group
CyclophosphamideCyclophosphamide injectionEC follow T group
DocetaxelDocetaxel injectionEC follow T group
Goserelin acetateZoladexTC follow endocrine
TamoxifenNolvadexTC follow endocrine
LetrozoleFemaraTC follow endocrine

Purpose

Breast cancer is the most common female malignancy in the world, and the leading cause of cancer-associated mortalities among women. Hormone receptors (HR) including ER and PR are the main prognostic factor for breast cancer patients. Breast cancer subtype was defined by ER, PR, HER2 and Ki67 status since the definition of intrinsic subtypes for breast cancer. Breast cancer which ER are positive have less aggressive and better long-term prognoses than other breast cancer subtype. Luminal B1 was definited as ER Positive, PR positive <20%, or Ki-67 ≥20% , and HER2-Negative. Although standard therapy to HR positive breast cancer is endocrine treatment, evidence reported that Luminal B1 breast cancers with lower PR expression are less sensitive to tamoxifen than luminal A breast cancers with higher PR expression, and the specific mechanism is not clear. We previously had a clinically analysed, and we found the Luminal B1 breast cancer had a significant proportion with 38%. Whether we need standard chemotherapy or chemotherapy based intensive endocrine therapy for those patients? In our research, we divided the patients with ER positive, PR negative, and HER-2 negative into two groups. One groups will be treated with 8 cycles of chemotherapy (EC×4-T×4). The other received 4 cycles of chemotherapy (TC×4) then will be given the intensive endocrine therapy (Goserelin acetate+Tamoxifen for young patients/Letrozole for postmenopausal patients). The primary endpoint is to assess disease-free survival (DFS) and overall survival (OS) in different regiments, the secondary endpoint is to assess the expression of female hormone levels. The correlation of the expression of female hormone levels with the clinical outcomes, so that the investigators could optimize adjuvant treatment regiment with luminal B1 breast cancer.

Detailed Description

      The trial is designed to investigative the risk and clinical benefit of chemotherapy and
      intensive endocrine therapy for Luminal B1 early-staged breast cancer. In this trial the
      investigators will randomly assign 200 primary breast cancer patients to receive four cycles
      of epirubicin and cyclophosphamide (EC) followed by four cycles of docetaxel(T), or four
      cycles of docetaxel and cyclophosphamide (TC) followed by intensive endocrine therapy
      (Goserelin acetate+Tamoxifen/Letrozole for young patients) . Patients with HER-2 positive was
      excluded. The patient's conditions will be assessed before, and after every four cycles of
      adjuvant chemotherapy to determine if there is any progression of the disease. The patient's
      conditions will be assessed every three months when they received the intensive endocrine
      therapy (Goserelin acetate+Tamoxifen for young patients/Letrozole for postmenopausal
      patients). Patients will be followed up for DFS and OS in different regiments, the secondary
      endpoint is to assess the expression of female hormone levels. The correlation of the
      expression of female hormone levels with the clinical outcomes, so that the investigators
      could optimize adjuvant treatment regiment with luminal B1 breast cancer.
    

Trial Arms

NameTypeDescriptionInterventions
EC follow T groupExperimentalEpirubicin 100mg/m2 on day 1 cyclophosphamide 600mg/m2 on day1 every 2 weeks for four cycles followed by docetaxel 100mg/m2 on day 1 every 3 weeks for four cycles
  • Epirubicin
  • Cyclophosphamide
  • Docetaxel
TC follow endocrineExperimentalDocetaxel 75mg/m2 on day 1 and cyclophosphamide 600mg/m2 on day 1 every 3 weeks for four cycles followed by goserelin acetate+tamoxifen for young patients/ letrozole for postmenopausal patients
  • Cyclophosphamide
  • Docetaxel
  • Goserelin acetate
  • Tamoxifen
  • Letrozole

Eligibility Criteria

        Inclusion Criteria:

          -  All patients were required to give written informed consent.

          -  Patients present with operable breast cancers that were diagnosed by histopathology
             and have no distant metastasis.

          -  Have no history of anti-cancer therapies including chemotherapy, radiation therapy,
             hormone therapy and surgical therapy

          -  Have normal cardiac functions by echocardiography

          -  ECOG scores are ≤ 0-1.

          -  Patients are disposed to practice contraception during the whole trial.

          -  The results of patients' blood tests are as follows:

        Hb ≥ 90 g/L WBC ≥ 3.0×109/L Plt ≥ 100×109/L Neutrophils ≥ 1.5×109/L ALT and AST ≤ 2.5 times
        of normal upper limit. TBIL ≤ 1.5 times of normal upper limit. Creatinine ≤ 1.5 times of
        normal upper limit.

          -  ER+ Her2- early-stage breast cancer

        Exclusion Criteria:

          -  Have other cancers at the same time or have the history of other cancers in recent
             five years, excluding the controlled skin basal cell carcinoma or skin squamous cell
             carcinoma or carcinoma in situ of cervix.

          -  Active infections

          -  Severe non-cancerous diseases.

          -  The patients are undergoing current administration of anti-cancer therapies, or are
             attending some other clinical trails.

          -  Inflammatory breast cancer.

          -  Pregnant or lactational, or patients refuse to practice contraception during the whole
             trial.- Page 5 of 5 -

          -  The patients are in some special conditions that they can't understand the written
             informed consent, such as they are demented or hawkish.

          -  Have allergic history of the chemotherapeutic agents.

          -  Bilateral breast cancers
      
Maximum Eligible Age:70 Years
Minimum Eligible Age:18 Years
Eligible Gender:Female
Healthy Volunteers:No

Primary Outcome Measures

Measure:Disease-free survival (DFS)
Time Frame:5 years
Safety Issue:
Description:To determine the percentage of disease-free survival (DFS) for the EC follow T arm and TC follow endocrine therapy arm separately.

Secondary Outcome Measures

Measure:Expression of female hormone levels
Time Frame:5 years
Safety Issue:
Description:To assess the association between the female hormone levels and the clinical outcomes
Measure:Overall survival (OS)
Time Frame:5 years
Safety Issue:
Description:To determine the percentage of Overall survival (OS) for the EC follow T arm and TC follow endocrine therapy arm separately.

Details

Phase:Phase 2/Phase 3
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Zhiyong Yu

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