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

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ClinicalTrials.gov Identifier: NCT02670109
Recruitment Status : Recruiting
First Posted : February 1, 2016
Last Update Posted : January 14, 2020
Sponsor:
Information provided by (Responsible Party):
Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran

Tracking Information
First Submitted Date  ICMJE January 28, 2016
First Posted Date  ICMJE February 1, 2016
Last Update Posted Date January 14, 2020
Actual Study Start Date  ICMJE February 1, 2018
Estimated Primary Completion Date November 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: April 22, 2019)
Overall Survival [ Time Frame: One year ]
Time from diagnosis to death from any cause.
Original Primary Outcome Measures  ICMJE
 (submitted: January 28, 2016)
Overall Survival [ Time Frame: One year ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: April 22, 2019)
Disease Free Survival [ Time Frame: One year ]
Time from ending primary treatment to relapse of the disease.
Original Secondary Outcome Measures  ICMJE
 (submitted: January 28, 2016)
Disease Free Survival [ Time Frame: One year ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Autologous Hematopoietic Stem Cell Transplantation as Adjuvant Treatment for Triple Negative Breast Cancer Patients
Official Title  ICMJE 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
Brief Summary 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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Triple-Negative Invasive Breast Carcinoma
  • Residual Tumor
Intervention  ICMJE
  • Drug: Carmustine
    300mg/m2, IV, in 3 hours, during day -4
    Other Name: BCNU
  • Drug: Cyclophosphamide
    80mg/kg, IV, in 2 hours, during two days -2, -3
    Other Name: Cytoxan
  • Drug: Carboplatin
    1400/m2, IV, in 1 hour, during day -3
    Other Name: Paraplatin
  • Procedure: Autologous Hematopoietic Stem Cell Transplantation
    Transfusion, in 3 hours, during day 0
    Other Name: Peripheral blood autologous HSCT
  • Drug: Busulfan
    16mg/kg, Oral, during day -4
    Other Name: Myleran
Study Arms  ICMJE Experimental: Unique

Patients will receive a high dose chemotherapy regimen, consisting in the administration of three medications: Carmustine (BCNU) 300mg/m2 or Busulfan 16 mg/kg (according to availability), Cyclophosphamide 80mg/kg, and Carboplatin 1400/m2.

Then they will undergo an Autologous Hematopoietic Stem Cell Transplantation.

Interventions:
  • Drug: Carmustine
  • Drug: Cyclophosphamide
  • Drug: Carboplatin
  • Procedure: Autologous Hematopoietic Stem Cell Transplantation
  • Drug: Busulfan
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: January 28, 2016)
20
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE November 2021
Estimated Primary Completion Date November 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
  • Disease progression during neoadjuvant therapy
  • Other tumors
  • Non triple negative breast cancer diagnosis
  • Pathological Complete Response achieved
Sex/Gender  ICMJE
Sexes Eligible for Study: Female
Ages  ICMJE 18 Years to 60 Years   (Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Eucario Leon Rodriguez, M.D. 525554870900 ext 2255 eucarios@hotmail.com
Contact: Monica M Rivera Franco, M.D.,MSc 525554870900 ext 2719 monrif_90d@hotmail.com
Listed Location Countries  ICMJE Mexico
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02670109
Other Study ID Numbers  ICMJE INCMNSZ REF 1239
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran
Study Sponsor  ICMJE Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Eucario Leon Rodriguez, M.D. Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran
Principal Investigator: Monica M Rivera Franco, M.D.,MSc Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran
PRS Account Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran
Verification Date January 2020

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