Clinical Trials /

Autologous Hematopoietic Stem Cell Transplantation as Adjuvant Treatment for Triple Negative Breast Cancer Patients

NCT02670109

Description:

Triple-negative breast cancer (TNBC) refers to any breast cancer that does not express estrogen receptor (ER), progesterone receptor (PR) or Her2/neu. Its incidence is approximately 180,000 cases per year. TNBC are known to be more aggressive with poor prognosis specially when no pathologic complete response (pCR) is achieved after neoadjuvant chemotherapy, with a higher risk of recurrence and a poor survival once that recurrence occurs. On the other hand, there is not a specific adjuvant or neoadjuvant treatment for these patients. Since autologous hematopoietic stem cell transplantation (HSCT) allows the usage of higher doses of chemotherapy, which results in higher cellular destruction with a decrease of hematological toxicity, it is proposed that this procedure is able to improve prognosis in TNBC patients with no pathologic complete response after neoadjuvant chemotherapy.

Related Conditions:
  • Breast Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Autologous Hematopoietic Stem Cell Transplantation as Adjuvant Treatment for Triple Negative Breast Cancer Patients
  • Official Title: High-dose Chemotherapy With Autologous Hematopoietic Stem Cell Transplantation as Adjuvant Treatment for Triple Negative Breast Cancer Patients Without Complete Pathological Response to Neoadjuvant Chemotherapy

Clinical Trial IDs

  • ORG STUDY ID: INCMNSZ REF 1239
  • NCT ID: NCT02670109

Conditions

  • Triple-Negative Invasive Breast Carcinoma
  • Residual Tumor

Interventions

DrugSynonymsArms
CarmustineBCNUUnique
CyclophosphamideCytoxanUnique
CarboplatinParaplatinUnique

Purpose

Triple-negative breast cancer (TNBC) refers to any breast cancer that does not express estrogen receptor (ER), progesterone receptor (PR) or Her2/neu. Its incidence is approximately 180,000 cases per year. TNBC are known to be more aggressive with poor prognosis specially when no pathologic complete response (pCR) is achieved after neoadjuvant chemotherapy, with a higher risk of recurrence and a poor survival once that recurrence occurs. On the other hand, there is not a specific adjuvant or neoadjuvant treatment for these patients. Since autologous hematopoietic stem cell transplantation (HSCT) allows the usage of higher doses of chemotherapy, which results in higher cellular destruction with a decrease of hematological toxicity, it is proposed that this procedure is able to improve prognosis in TNBC patients with no pathologic complete response after neoadjuvant chemotherapy.

Detailed Description

      Triple-negative breast cancer (TNBC) accounts for approximately 15%-25% of all breast cancer
      cases. TNBC are usually high-grade tumors, presented among younger women, African American
      and Hispanic women have a higher risk; generally in advanced stages when diagnosed, with
      visceral recurrence (liver, lung, brain). Standard treatment is surgery with adjuvant
      chemotherapy and radiotherapy. As a variation, neoadjuvant chemotherapy is very frequently
      used for triple-negative breast cancers, however, there is a lack of specific agents for this
      subset of patients, and, pathologic complete response does correlate with overall survival.
      At the moment, no optimal chemotherapy exists for TNBC patients who do not achieve a pCR.

      According to the German group, in the triple negative subset, 31% of patients with
      neoadjuvant chemotherapy achieved pathologic complete response (pCR), which correlates with
      progression free survival (HR 6.02 for those who do not achieve pCR), and an overall survival
      (HR 12.41 for those who do not achieve pCR).

      The usage of high-dose chemotherapy with autologous HSCT, is one of the therapies that have
      been studied in the patients with localized breast cancer aiming to improve its outcome.
      Autologous HSCT allows higher chemotherapy doses, which results in higher tumor cells
      destruction. Since 1980, several phase II studies were performed with high-dose chemotherapy
      and autologous HSCT, with an apparently initial benefit, thus this strategy was widely used
      outside controlled clinical trials. Afterward, the randomized studies did not show benefit in
      overall survival, causing this strategy to be abandoned.

      It is important to highlight studies heterogeneity by means of different treatment options in
      both experimental and control group, besides, advances in autologous HSCT has significantly
      reduced the complexity, mobility, and mortality related to the chemotherapy treatment.

      Two published studies including patients with localized TNBC, showed benefit in the
      progression free survival in the high-dose chemotherapy group, with a tendency to improved
      overall survival. One of them was performed by a german group, including patients with at
      least 9 positive nodes, which were randomized to receive two cycles of conventional dose
      chemotherapy followed by two cycles of high-dose chemotherapy with autologous HSCT versus
      four cycles of conventional dose chemotherapy followed by three cycles of dense dose
      chemotherapy, with granulocyte colony-stimulating factor (G-CSF) administration. Progression
      free survival was 76 months in the group of high dose chemotherapy versus 40.6 months in the
      conventional chemotherapy group, with an overall survival of 60 versus 44%, being
      statistically significant.

      Our hypothesis is that patients with TNBC with a high risk of recurrence (no pCR) who undergo
      high-dose chemotherapy followed by autologous HSCT will have a higher overall survival
      compared to those who do not undergo the above mentioned treatment.
    

Trial Arms

NameTypeDescriptionInterventions
UniqueExperimentalPatients will receive a high dose chemotherapy regimen, consisting in the administration of three medications: Carmustine (BCNU) 300mg/m2, Cyclophosphamide 80mg/kg, and carboplatin 1400/m2. Then they will undergo an Autologous Hematopoietic Stem Cell Transplantation.
  • Carmustine
  • Cyclophosphamide
  • Carboplatin

Eligibility Criteria

        Inclusion Criteria:

          -  Triple Negative Breast Cancer diagnosis (no expression of hormonal receptors or
             Her2/neu)

          -  Previous administration of neoadjuvant chemotherapy (60 days maximum)

          -  No evidence of metastatic disease at inclusion

          -  Residual tumor in the breast and/or lymph nodes

          -  Normal renal, liver, heart, lung, and hematopoietic function

        Exclusion Criteria:

          -  Pregnancy

          -  Other tumors

          -  Non triple negative breast cancer diagnosis

          -  Pathological Complete Response achieved
      
Maximum Eligible Age:60 Years
Minimum Eligible Age:18 Years
Eligible Gender:Female
Healthy Volunteers:No

Primary Outcome Measures

Measure:Overall Survival
Time Frame:One year
Safety Issue:
Description:

Secondary Outcome Measures

Measure:Disease Free Survival
Time Frame:One year
Safety Issue:
Description:

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran

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