Triple-Negative Invasive Breast CarcinomaPhase 2NCT02670109
Autologous Hematopoietic Stem Cell Transplantation as Adjuvant Treatment for Triple Negative Breast Cancer Patients
A Phase 2 study testing Carmustine, Cyclophosphamide and Carboplatin in people with Triple-Negative Invasive Breast Carcinoma and Residual Tumor, run by Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran at 1 site in Mexico.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 60 years, women only
- Conditions the study is for
- Triple-Negative Invasive Breast Carcinoma, Residual Tumor
- What is being tested?
- Carmustine, Cyclophosphamide and Carboplatin
- Type of treatment
- Pill or oral medicine, Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 20 participants
- Where
- 1 siteMexico
- Study dates
- 1 Feb 2018to Nov 2021
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 60 years
- Women only
- No healthy volunteers
- Adult
Who may be able to join
- 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
Who cannot join
- Pregnancy
- Disease progression during neoadjuvant therapy
- Other tumors
- Non triple negative breast cancer diagnosis
- Pathological Complete Response achieved
Trial locations and contacts
1 site in 1 country.
Mexico1 site, 1 recruiting
- Recruiting
Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran
Mexico City, Mexico City, 14080
Eucario Leon Rodriguez, M.D., 525554870900 ext. 2255, eucarios@hotmail.com
Monica M Rivera Franco, M.D., 525554870900 ext. 2719, monrif90d@gmail.com
About this study
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
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.
Read the 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.
- Being tested
- Carmustine, Cyclophosphamide, Carboplatin, Autologous Hematopoietic Stem Cell Transplantation, Busulfan
- Medical subject headings
- Neoplasm, Residual
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CarmustineDrug
Also called BCNU
300mg/m2, IV, in 3 hours, during day -4
CyclophosphamideDrug
Also called Cytoxan
80mg/kg, IV, in 2 hours, during two days -2, -3
CarboplatinDrug
Also called Paraplatin
1400/m2, IV, in 1 hour, during day -3
Autologous Hematopoietic Stem Cell TransplantationProcedure or surgery
Also called Peripheral blood autologous HSCT
Transfusion, in 3 hours, during day 0
BusulfanDrug
Also called Myleran
16mg/kg, Oral, during day -4
| Study group | Role | What they receive |
|---|---|---|
| Unique | Experimental | 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. Receives: Drug: Carmustine; Drug: Cyclophosphamide; Drug: Carboplatin; Procedure: Autologous Hematopoietic Stem Cell Transplantation; Drug: Busulfan |
What is being measured
The primary outcome is the main question the study is designed to answer.
Overall Survival
Time from diagnosis to death from any cause.
Measured: One year
Secondary outcomes (1)
Disease Free Survival
Time from ending primary treatment to relapse of the disease.
Measured: One year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Feb 2016 (estimated)
- Study start1 Feb 2018
- Primary completionNov 2020 (estimated)
- Study completionNov 2021 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Triple-Negative Invasive Breast CarcinomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 20 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Eucario Leon Rodriguez, M.D., Principal investigator, Instituto Nacional de Ciencias Medicas y Nutricion Salvador ZubiranMonica M Rivera Franco, M.D.,MSc, Principal investigator, Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02670109
- Sponsor's protocol ID
- INCMNSZ REF 1239
- Status last verified
- Jan 2020
- First submitted
- 28 Jan 2016
- Last updated
- 14 Jan 2020
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 14 Jan 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT02670109
- Acronym / sponsor ID
- INCMNSZ REF 1239
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 20 participants (estimated)
- Lead sponsor
- Instituto Nacional de Ciencias Medicas y Nutricion Salvador ZubiranUniversity, hospital or other
- Study start
- 1 Feb 2018 (actual)
- Primary completion
- Nov 2020 (estimated)
- Study completion
- Nov 2021 (estimated)
- First posted
- 1 Feb 2016 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Unique | Experimental | Drug: Carmustine, Drug: Cyclophosphamide, Drug: Carboplatin, Procedure: Autologous Hematopoietic Stem Cell Transplantation, Drug: BusulfanPatients 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. |
Who may qualify
- Ages
- 18 to 60 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (5 listed)
- 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
Key exclusion criteria (5 listed)
- Pregnancy
- Disease progression during neoadjuvant therapy
- Other tumors
- Non triple negative breast cancer diagnosis
- Pathological Complete Response achieved
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| CarmustineAlso: BCNU300mg/m2, IV, in 3 hours, during day -4 | Drug | Unique |
| CyclophosphamideAlso: Cytoxan80mg/kg, IV, in 2 hours, during two days -2, -3 | Drug | Unique |
| CarboplatinAlso: Paraplatin1400/m2, IV, in 1 hour, during day -3 | Drug | Unique |
| Autologous Hematopoietic Stem Cell TransplantationAlso: Peripheral blood autologous HSCTTransfusion, in 3 hours, during day 0 | Procedure or surgery | Unique |
| BusulfanAlso: Myleran16mg/kg, Oral, during day -4 | Drug | Unique |
Primary outcome
Overall Survival
Time frame: One year
Time from diagnosis to death from any cause.
1 secondary outcome
Disease Free Survival
Time frame: One year
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Jan 2020.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Eucario Leon Rodriguez, M.D. principal investigator
Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran
Monica M Rivera Franco, M.D.,MSc principal investigator
Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Carmustine, Cyclophosphamide and Carboplatin in people with Triple-Negative Invasive Breast Carcinoma and Residual Tumor, run by Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran at 1 site in Mexico.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 14 Jan 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Mexico. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Eucario Leon Rodriguez, M.D. (525554870900 ext. 2255, eucarios@hotmail.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Overall Survival (time frame: One year). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Jan 2020.