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

NCT ID: NCT02670109

Last Updated: 2020-01-14

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE2
• Total Enrollment: 20 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-02-01
• Study Completion Date: 2021-11-30

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.

Conditions

Triple-Negative Invasive Breast Carcinoma; Residual Tumor

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

Carmustine

Intervention Type: DRUG

300mg/m2, IV, in 3 hours, during day -4

Cyclophosphamide

Intervention Type: DRUG

80mg/kg, IV, in 2 hours, during two days -2, -3

Carboplatin

Intervention Type: DRUG

1400/m2, IV, in 1 hour, during day -3

Autologous Hematopoietic Stem Cell Transplantation

Intervention Type: PROCEDURE

Transfusion, in 3 hours, during day 0

Busulfan

Intervention Type: DRUG

16mg/kg, Oral, during day -4

Interventions

Carmustine

300mg/m2, IV, in 3 hours, during day -4

Intervention Type: DRUG

Cyclophosphamide

80mg/kg, IV, in 2 hours, during two days -2, -3

Intervention Type: DRUG

Carboplatin

1400/m2, IV, in 1 hour, during day -3

Intervention Type: DRUG

Autologous Hematopoietic Stem Cell Transplantation

Transfusion, in 3 hours, during day 0

Intervention Type: PROCEDURE

Busulfan

16mg/kg, Oral, during day -4

Intervention Type: DRUG

Other Intervention Names

BCNU; Cytoxan; Paraplatin; Peripheral blood autologous HSCT; Myleran

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
• Disease progression during neoadjuvant therapy
• Other tumors
• Non triple negative breast cancer diagnosis
• Pathological Complete Response achieved

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 60 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Eucario Leon Rodriguez, M.D.

Role: PRINCIPAL_INVESTIGATOR

Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran

Monica M Rivera Franco, M.D.,MSc

Role: PRINCIPAL_INVESTIGATOR

Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran

Locations

Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran

Mexico City, Mexico City, Mexico

Site Status: RECRUITING

Countries

Mexico

Central Contacts

Eucario Leon Rodriguez, M.D.

Role: CONTACT

eucarios@hotmail.com

525554870900 ext. 2255

Monica M Rivera Franco, M.D.,MSc

Role: CONTACT

monrif_90d@hotmail.com

525554870900 ext. 2719

Facility Contacts

Eucario Leon Rodriguez, M.D.

Role: primary

eucarios@hotmail.com

525554870900 ext. 2255

Monica M Rivera Franco, M.D.

Role: backup

monrif90d@gmail.com

525554870900 ext. 2719

Other Identifiers

INCMNSZ REF 1239

Identifier Type: -

Identifier Source: org_study_id