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

January 10, 2020 updated by: Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran

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

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.

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

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

Interventional

Enrollment (Anticipated)

20

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • Mexico
    • Distrito Federal
      • Mexico City, Distrito Federal, Mexico, 14080
        • Recruiting
        • Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran
        • Contact:
        • Sub-Investigator:
          • Alejandra Armengol Alonso, M.D.

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 60 years (Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Female

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
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.
Drug: Carmustine
300mg/m2, IV, in 3 hours, during day -4
Other Names:
  • BCNU
Drug: Cyclophosphamide
80mg/kg, IV, in 2 hours, during two days -2, -3
Other Names:
  • Cytoxan
Drug: Carboplatin
1400/m2, IV, in 1 hour, during day -3
Other Names:
  • Paraplatin
Procedure: Autologous Hematopoietic Stem Cell Transplantation
Transfusion, in 3 hours, during day 0
Other Names:
  • Peripheral blood autologous HSCT
Drug: Busulfan
16mg/kg, Oral, during day -4
Other Names:
  • Myleran

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Overall Survival
Time Frame: One year
Time from diagnosis to death from any cause.
One year

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Disease Free Survival
Time Frame: One year
Time from ending primary treatment to relapse of the disease.
One year

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

February 1, 2018

Primary Completion (Anticipated)

November 1, 2020

Study Completion (Anticipated)

November 1, 2021

Study Registration Dates

First Submitted

January 28, 2016

First Submitted That Met QC Criteria

January 28, 2016

First Posted (Estimate)

February 1, 2016

Study Record Updates

Last Update Posted (Actual)

January 14, 2020

Last Update Submitted That Met QC Criteria

January 10, 2020

Last Verified

January 1, 2020

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • INCMNSZ REF 1239

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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