Triple Negative Breast CancerPhase 2NCT02511847
Trial of Afatinib With Paclitaxel for Neoadjuvant Therapy of TNBC and Research of Biomarkers of Afatinib
A Phase 2 study testing Afatinib in people with Triple Negative Breast Cancer, run by National Taiwan University Hospital at 1 site in Taiwan.
Trial summary
[Background]: Triple-negative breast cancer (TNBC) is defined by a lack of expression of both estrogen and progesterone receptor as well as human epidermal growth factor receptor 2 (HER-2). Read more about this study
- Who is it for?
- Ages 20 years and older, women only
- Conditions the study is for
- Triple Negative Breast Cancer
- What is being tested?
- Afatinib
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 40 participants
- Where
- 1 siteTaiwan
- Study dates
- Aug 2015to Jul 2017
- 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 20 years and older
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Female patients, age ≥20 years
- Histologically confirmed invasive ER-, PR-, and HER2-negative (triple-negative) adenocarcinoma of the breast
- Triple-negative tumors are defined as:
- For HER2-negative: Fluorescence in situ hybridization (FISH)-negative (defined by ratio <2.0) or Immunohistochemical (IHC) 0, IHC 1+, or IHC 2+ or IHC 3+and FISH-negative (defined by ratio <2.0) ii. For ER- and PR-negative: < 5% tumor staining by immunohistochemistry (IHC)
- The first TNBC 20 patients with or without EGFR expression or mutation are eligible. Interim analysis of response rate will be calculated to determine the criteria of 21 to 40 patients.
- All of the newly diagnosed TNBC patients should be met the following criteria: clinical node-positive with any T stage patents or clinical node-negative patients with cT2-4. cT1N0M0 lesions are excluded. Patients with metastatic disease are excluded. The measurement method of tumor size can be by physical exam and/or image study.
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- Eastern Cooperative Oncology Group performance status (ECOG PS) 0-1.
- Within 2 weeks prior randomization:
- Adequate bone marrow function, hepatic function, and renal function. ii. Controlled blood pressure with or without antihypertensive treatment iii. Normal prothrombin time (PT) and partial thromboplastin time (PTT) iv. Adequate cardiac function assessed by 12-lead ECG and if clinically indicated echocardiography to document LVEF
- Bilateral, synchronous breast cancer is allowed if one primary tumor meets the inclusion criteria.
- Adequate bone marrow function defined as WBC ≥3.5 x 109/L, ANC ≥1.5 x 109/L, platelets ≥LLN, and hemoglobin ≥10 g/dL.
- Adequate liver function defined as total serum bilirubin ≤1.5X ULN and serum transaminases ≤2.5X ULN
- Adequate renal function defined as creatinine ≤1.5X ULN
- Able and willing to give informed consent and comply with the protocol
- Written informed consent obtained prior to any Screening/baseline procedures
- Knowledge of the investigational nature of the study and ability to provide consent for study participation; and ability and willingness to comply with study visits, treatment, testing, and other study procedures
Who cannot join
- ER+ (>5%) or PR+ (>5%) or Her-2 overexpression
- Active second malignancy during the last five years except non melanomatous skin cancer or carcinoma in situ of the cervix.
- Prior chemotherapy, radiotherapy or targeted therapy including afatinib or Her-2 or EGFR inhibitors.
- Participation in another interventional clinical trial in the preceding 30 days prior to trial.
- Patients with other concurrent severe and/or uncontrolled medical disease or infection which could compromise participation in the study
- Prior hypersensitivity reactions to a taxane or to Cremophor® EL (polyoxyethylated castor oil)
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- Pregnant or breast feeding (lactating) women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by positive β-HCG laboratory test (serum > 5 mIU/mL)
- Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using highly effective methods of contraception during dosing and for at least 180 days after study treatment. Highly effective contraception methods include:
- True abstinence in line with the preferred and usual lifestyle of the subject
- Female subject or male partner sterilization or
- Combination of any two of the following (a+b or a+c, or b+c):
- Use of oral, injected or implanted hormonal methods of contraception
- Placement of an intrauterine device (IUD) or intrauterine system (IUS)
- Barrier methods of contraception: condom for male partner or occlusive cap
- (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/vaginal suppository
- Patients with any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule; those conditions should be discussed with the patient before registration in the trial.
Trial locations and contacts
1 site in 1 country.
Taiwan1 site, 1 recruiting
- Recruiting
National Taiwan University Hospital
Taipei, Taiwan, 110
Chiun-Sheng Huang, 886-23123456 ext. 65080
About this study
Official title: An Open Label, Phase II Trial of Afatinib With Paclitaxel for the Neoadjuvant Treatment of Triple-Negative Breast Cancer and Research of Biomarkers of Activity and Efficacy of Afatinib
[Background]: Triple-negative breast cancer (TNBC) is defined by a lack of expression of both estrogen and progesterone receptor as well as human epidermal growth factor receptor 2 (HER-2). TNBC is characterized by distinct molecular, histological and unfavorable clinical features despite the high rates of response to chemotherapy. Based on the above reasons, it is important to emergently develop novel therapies and/or treatment strategies to increase treatment efficacies and the survival rate of TNBC.
[Rationale]: Overexpression of epidermal growth factor receptor (EGFR/ErbB1) and EGFR mutation have been reported in TNBC and may therefore be a valid target for anti-tumor therapy in TNBC. Afatinib (BIBW 2992) is an ErbB-family blocker that irreversibly inhibits signaling from all relevant ErbB-family dimers. Afatinib has demonstrated preclinical activity in triple-negative breast cancer cell lines and xenograft models of breast cancer, and clinical activity in phase I studies. Based on the assumption that uncontrolled ErbB-signaling is directly related to an increased oncogenic potential in TNBC, the studying afatinib in the neoadjuvant treatment of TNBC patients is important and provides a novel therapy.
Read more
[Aims] The primary endpoint is to evaluate the pathologic complete response of the combination of afatinib and weekly paclitaxel in TNBC patients receiving neoadjuvant treatment. The secondary endpoints are to evaluate the clinical response and safety of afatinib with and without paclitaxel, and to explore the different afatinib-affecting downstream molecular pathways as well as potential biomarkers predicting the response of afatinib with and without paclitaxel.
[Patients and methods]: Patients with TNBC (clinical T2-T3, N0-N1, M0; clinical T1-3, N1-2, M0; or any T4a tumor) and received neoadjuvant treatment will included in this open, label, multi-center phase II study. Our schema is as follows: (1) Afatinib 40 mg per day for 14 days, then evaluation, every subject will go into the following phase no matter whether she had response or not (2) the following phase (the combination with afatinib and paclitaxel): Afatinib 40 mg per day, day 1 to day 21, in combination with paclitaxel 80 mg/m² on days 1, 8, 15 in a 3-weekly course. In addition to the clinical assessment, we will evaluate the potential predictive biological markers of activity of Afatinib with and without paclitaxel and dynamic changes of molecular makers ([serum and tissue samples: before treatment, 2 weeks after treatment, and operation timing]; potential molecules, such as EGFR, EGFR-signaling, FGFR, FGFR-signaling, ERK, p53, NF-κB, and etc. were evaluated through the immunohistochemical stains, mutation analysis, mRNA [RT-PCR], single nucleotide polymorphism analysis, and FISH analysis). In addition, the genetic expression profiles will be compared between afatinib-responsive and afatinib-unresponsive samples.
[Expected Results]: The promising clinical activity, tolerable toxicity, and potential biomarkers of afatinib with and without paclitaxel in TNBC patients receiving neoadjuvant setting will be demonstrated. The results from this study can be used to conduct a larger trial that would allow us to confirm or validate the hypotheses generated.
Read the detailed description
Objects: Phase II study
Primary Objective :
To evaluate the efficacy of combination of afatinib and weekly paclitaxel as assessed by pathologicalresponse in the residual tumor.
Secondary Objectives:
- Efficacy of afatinib as assessed by the ultrasound of the breast.
- Adverse effect of afatinib monotherapy and the combination of afatinib and weekly paclitaxel.
- Correlation between baseline potential biomarkers and radiological response of afatinib monotherapy.
- Correlation between down- or up-regulation of potential biomarkers (in pre-treatment biopsy and surgical specimen) and radiological response to afatinib and paclitaxel.
- To identify the pharmacodynamic biomarkers, the following translational researches will be carried out on initial tumor biopsy and surgical specimen.
- To evaluate the dynamic changes of circulating tumor cells and cell-free DNA after afatinib monotherapy and after the combination of afatinib and weekly paclitaxel.
- Conditions
- Triple Negative Breast Cancer
- Being tested
- Afatinib
- Keywords
- Breast Cancer, EGFR, Afatinib, Paclitaxel, Pathologic complete remission
- Medical subject headings
- Triple Negative Breast Neoplasms, Breast Neoplasms, Pathologic Complete Response
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AfatinibDrug
- Afatinib 40 mg per day for 14 days, then evaluation, every subject will go into the following phase no matter whether she had response or not
- Afatinib 40 mg per day, day 1 to day 21, in combination with paclitaxel 80 mg/m² on days 1, 8, 15 in a 3-weekly course.
| Study group | Role | What they receive |
|---|---|---|
| single-arm | Other | Drug: Afatinib (single group assignment)
1. First phase: Afatinib montherapy
2. The following phases: combination with oral afatinib and weekly paclitaxel in a 3-weekly course for total of four courses. Receives: Drug: Afatinib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Efficacy of pathologic response of the combination of afatinib and weekly paclitaxel
Evaluation of the pathologic complete response of the combination of afatinib and weekly paclitaxel in TNBC patients with neoadjuvant treatment.
Measured: 2 years
Secondary outcomes (6)
Efficacy of afatinib
The radiologic response will be assessed on ultrasound of the breast.
Measured: 2 years
Adverse effect of afatinib monotherapy and the combination of afatinib and weekly paclitaxel
Measured: 2 years
Correlation between potential biomarkers and radiological response of afatinib montherapy
Measured: 2 years
Correlation between down- or up-regulation of potential biomarkers and radiological response to afatinib and paclitaxel
Measured: 2 years
Identification of the pharmacodynamic biomarkers by initial tumor biopsy and surgical specimen
Measured: 2 years
Evaluation of the dynamic changes of circulating tumor cells and cell-free DNA after afatinib monotherapy and after the combination of afatinib and weekly paclitaxel
circulating tumor cells is a new technigue compatible with cell search.
Measured: 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Jul 2015 (estimated)
- Study startAug 2015
- Primary completionJul 2017 (estimated)
- Study completionJul 2017 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Triple Negative Breast CancerStudies of the same condition, open and under way.
- More trials run by National Taiwan University HospitalThe sponsor's other registered studies.
- 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
- 40 participants (estimated)
Sponsor and investigators
- Lead sponsor
- National Taiwan University Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Chiun-Sheng Huang, PhD, Principal investigator, Department of Surgery, National Taiwan University Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02511847
- Sponsor's protocol ID
- 201408024MIPC
- Status last verified
- Apr 2016
- First submitted
- 16 Jul 2015
- Last updated
- 15 Apr 2016
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 15 Apr 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Open Label, Phase II Trial of Afatinib With Paclitaxel for the Neoadjuvant Treatment of Triple-Negative Breast Cancer and Research of Biomarkers of Activity and Efficacy of Afatinib
- ClinicalTrials.gov ID
- NCT02511847
- Acronym / sponsor ID
- 201408024MIPC
- Conditions
- Triple Negative Breast Cancer
- Keywords
- Breast Cancer, EGFR, Afatinib, Paclitaxel, Pathologic complete remission
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 40 participants (estimated)
- Lead sponsor
- National Taiwan University HospitalUniversity, hospital or other
- Study start
- Aug 2015
- Primary completion
- Jul 2017 (estimated)
- Study completion
- Jul 2017 (estimated)
- First posted
- 30 Jul 2015 (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.
[Background]: Triple-negative breast cancer (TNBC) is defined by a lack of expression of both estrogen and progesterone receptor as well as human epidermal growth factor receptor 2 (HER-2). TNBC is characterized by distinct molecular, histological and unfavorable clinical features despite the high rates of response to chemotherapy. Based on the above reasons, it is important to emergently develop novel therapies and/or treatment strategies to increase treatment efficacies and the survival rate of TNBC.
[Rationale]: Overexpression of epidermal growth factor receptor (EGFR/ErbB1) and EGFR mutation have been reported in TNBC and may therefore be a valid target for anti-tumor therapy in TNBC. Afatinib (BIBW 2992) is an ErbB-family blocker that irreversibly inhibits signaling from all relevant ErbB-family dimers. Afatinib has demonstrated preclinical activity in triple-negative breast cancer cell lines and xenograft models of breast cancer, and clinical activity in phase I studies. Based on the assumption that uncontrolled ErbB-signaling is directly related to an increased oncogenic potential in TNBC, the studying afatinib in the neoadjuvant treatment of TNBC patients is important and provides a novel therapy.
[Aims] The primary endpoint is to evaluate the pathologic complete response of the combination of afatinib and weekly paclitaxel in TNBC patients receiving neoadjuvant treatment. The secondary endpoints are to evaluate the clinical response and safety of afatinib with and without paclitaxel, and to explore the different afatinib-affecting downstream molecular pathways as well as potential biomarkers predicting the response of afatinib with and without paclitaxel.
[Patients and methods]: Patients with TNBC (clinical T2-T3, N0-N1, M0; clinical T1-3, N1-2, M0; or any T4a tumor) and received neoadjuvant treatment will included in this open, label, multi-center phase II study. Our schema is as follows: (1) Afatinib 40 mg per day for 14 days, then evaluation, every subject will go into the following phase no matter whether she had response or not (2) the following phase (the combination with afatinib and paclitaxel): Afatinib 40 mg per day, day 1 to day 21, in combination with paclitaxel 80 mg/m² on days 1, 8, 15 in a 3-weekly course. In addition to the clinical assessment, we will evaluate the potential predictive biological markers of activity of Afatinib with and without paclitaxel and dynamic changes of molecular makers ([serum and tissue samples: before treatment, 2 weeks after treatment, and operation timing]; potential molecules, such as EGFR, EGFR-signaling, FGFR, FGFR-signaling, ERK, p53, NF-κB, and etc. were evaluated through the immunohistochemical stains, mutation analysis, mRNA [RT-PCR], single nucleotide polymorphism analysis, and FISH analysis). In addition, the genetic expression profiles will be compared between afatinib-responsive and afatinib-unresponsive samples.
[Expected Results]: The promising clinical activity, tolerable toxicity, and potential biomarkers of afatinib with and without paclitaxel in TNBC patients receiving neoadjuvant setting will be demonstrated. The results from this study can be used to conduct a larger trial that would allow us to confirm or validate the hypotheses generated.
Detailed description
Objects: Phase II study
Primary Objective :
To evaluate the efficacy of combination of afatinib and weekly paclitaxel as assessed by pathologicalresponse in the residual tumor.
Secondary Objectives:
- Efficacy of afatinib as assessed by the ultrasound of the breast.
- Adverse effect of afatinib monotherapy and the combination of afatinib and weekly paclitaxel.
- Correlation between baseline potential biomarkers and radiological response of afatinib monotherapy.
- Correlation between down- or up-regulation of potential biomarkers (in pre-treatment biopsy and surgical specimen) and radiological response to afatinib and paclitaxel.
- To identify the pharmacodynamic biomarkers, the following translational researches will be carried out on initial tumor biopsy and surgical specimen.
- To evaluate the dynamic changes of circulating tumor cells and cell-free DNA after afatinib monotherapy and after the combination of afatinib and weekly paclitaxel.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| single-arm | Other | Drug: AfatinibDrug: Afatinib (single group assignment) 1. First phase: Afatinib montherapy 2. The following phases: combination with oral afatinib and weekly paclitaxel in a 3-weekly course for total of four courses. |
Who may qualify
- Ages
- 20 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (16 listed)
- Female patients, age ≥20 years
- Histologically confirmed invasive ER-, PR-, and HER2-negative (triple-negative) adenocarcinoma of the breast
- Triple-negative tumors are defined as:
- The first TNBC 20 patients with or without EGFR expression or mutation are eligible. Interim analysis of response rate will be calculated to determine the criteria of 21 to 40 patients.
- All of the newly diagnosed TNBC patients should be met the following criteria: clinical node-positive with any T stage patents or clinical node-negative patients with cT2-4. cT1N0M0 lesions are excluded. Patients with metastatic disease are excluded. The measurement method of tumor size can be by physical exam and/or image study.
Key exclusion criteria (16 listed)
- ER+ (>5%) or PR+ (>5%) or Her-2 overexpression
- Active second malignancy during the last five years except non melanomatous skin cancer or carcinoma in situ of the cervix.
- Prior chemotherapy, radiotherapy or targeted therapy including afatinib or Her-2 or EGFR inhibitors.
- Participation in another interventional clinical trial in the preceding 30 days prior to trial.
- Patients with other concurrent severe and/or uncontrolled medical disease or infection which could compromise participation in the study
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 |
|---|---|---|
| Afatinib1. Afatinib 40 mg per day for 14 days, then evaluation, every subject will go into the following phase no matter whether she had response or not 2. Afatinib 40 mg per day, day 1 to day 21, in combination with paclitaxel 80 mg/m² on days 1, 8, 15 in a 3-weekly course. | Drug | single-arm |
Primary outcome
Efficacy of pathologic response of the combination of afatinib and weekly paclitaxel
Time frame: 2 years
Evaluation of the pathologic complete response of the combination of afatinib and weekly paclitaxel in TNBC patients with neoadjuvant treatment.
6 secondary outcomes
Efficacy of afatinib
Time frame: 2 years
Adverse effect of afatinib monotherapy and the combination of afatinib and weekly paclitaxel
Time frame: 2 years
Correlation between potential biomarkers and radiological response of afatinib montherapy
Time frame: 2 years
Correlation between down- or up-regulation of potential biomarkers and radiological response to afatinib and paclitaxel
Time frame: 2 years
Identification of the pharmacodynamic biomarkers by initial tumor biopsy and surgical specimen
Time frame: 2 years
Evaluation of the dynamic changes of circulating tumor cells and cell-free DNA after afatinib monotherapy and after the combination of afatinib and weekly paclitaxel
Time frame: 2 years
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Apr 2016.
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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.
Chiun-Sheng Huang, PhD principal investigator
Department of Surgery, National Taiwan University Hospital
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 Afatinib in people with Triple Negative Breast Cancer, run by National Taiwan University Hospital at 1 site in Taiwan.
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 16 inclusion and 16 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 15 Apr 2016. 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 Taiwan. 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 PeiYing Liu (886-23123456 ext. 65080, tbcc.org@gmail.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Efficacy of pathologic response of the combination of afatinib and weekly paclitaxel (time frame: 2 years). 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 15 Apr 2016.