Triple Negative Breast CancerPhase 3NCT03876886
The Trial Comparing Dose-dense AC-T With TP as Adjuvant Therapy for TNBC With Homologous Recombination Repair Deficiency
A Phase 3 study testing Epirubicin, Cyclophosphamide and Paclitaxel in people with Triple Negative Breast Cancer, run by Chinese Academy of Medical Sciences at 1 site in China.
Trial summary
The purpose of this trial is to compare the 3-year disease-free survival of dose-dense epirubicin and cyclophosphamide followed by paclitaxel with paclitaxel plus carboplatin as adjuvant therapy for triple-negative breast cancer with homologous recombination repair deficiency. Read more about this study
- Who is it for?
- Ages 18 to 60 years
- Conditions the study is for
- Triple Negative Breast Cancer
- What is being tested?
- Epirubicin, Cyclophosphamide and Paclitaxel
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 200 participants
- Where
- 1 siteChina
- Study dates
- 22 Feb 2019to Dec 2024
- Phase
- Phase 3
- 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
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- 18-60 years
- Histologically confirmed adenocarcinoma of the breast, complete tumor removal by either modified radical mastectomy or local excision plus axillary lymph node dissection (i.e., breast conservation therapy) or sentinel node biopsy. (Tumor-free margins at least 1 mm for both invasive and noninvasive carcinoma except for lobular carcinoma in situ (less than 1 mm allowed);
- Histologically confirmed ER(-) PR(-) and HER-2(IHC(immunohistochemistry) 0-1+ or FISH (fluorescence in situ hybridization) negative)
- Next-generation sequencing confirmed homologous recombination repair deficiency
- Meet one of the following criteria:
- Positive axillary lymph nodes; (2) Negative axillary lymph nodes with at least one of the following risk factors: age<= 35 years; grade III; infiltrative tumor size > 2cm; intravascular tumor embolus; Ki-67>=50%.
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- 6. Eastern Cooperative Oncology Group (ECOG) Performance Score 0-1 7. Adequate bone marrow reserve with ANC > 1500, HGB > 9g/dL and platelets > 100,000.
- 8. Adequate renal function with serum creatinine < 2.0. 9. Adequate hepatic reserve with serum bilirubin < 2.0, AST/ALT < 2X the upper limit of normal, and alkaline phosphatase < 5X the upper limit of normal. Serum bilirubin > 2.0 is acceptable in the setting of known Gilbert's syndrome.
- 10. Not pregnant, and on appropriate birth control if of child-bearing potential.
- 11. Written informed consent according to the local ethics committee requirements.
Who cannot join
- Prior systemic treatment of breast cancer, including chemotherapy;
- Metastatic breast cancer;
- Patients with medical conditions that indicate intolerant to adjuvant therapy and related treatment, including uncontrolled pulmonary disease, diabetes mellitus, severe infection, active peptic ulcer, coagulation disorder, connective tissue disease or myelo-suppressive disease;
- Has active hepatitis B or hepatitis C with abnormal liver function tests (LFTs) or is known to be HIV positive;
- Contraindication for using dexamethasone;
- History of congestive heart failure, uncontrolled or symptomatic angina pectoris, arrhythmia or myocardial infarction; poorly controlled hypertension (systolic BP>180 mmHg or diastolic BP>100 mmHg);
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- Pregnant or breast feeding.
- Hepatic, renal, or bone marrow dysfunction as detailed above.
- Known severe hypersensitivity to any drugs in this study;
- Treatment with any investigational drugs within 30 days before the beginning of study treatment.
Trial locations and contacts
1 site in 1 country.
China1 site, 1 recruiting
- Recruiting
National Cancer Center, Cancer Hospital/Chinese Academy of Medical Sciences and Peking Union Medical College
Beijing, Beijing Municipality, 100021
Binghe XU, M.D., 86-10-88788826, xubinghe@medmail.com.cn
About this study
Official title: Randomized Phase Ⅲ Trial Comparing Dose-dense Epirubicin and Cyclophosphamide Followed by Paclitaxel With Paclitaxel Plus Carboplatin as Adjuvant Therapy for Triple-negative Breast Cancer With Homologous Recombination Repair Deficiency
The purpose of this trial is to compare the 3-year disease-free survival of dose-dense epirubicin and cyclophosphamide followed by paclitaxel with paclitaxel plus carboplatin as adjuvant therapy for triple-negative breast cancer with homologous recombination repair deficiency.
The other purpose of this trial is to observe the patient's tolerance.
Read the detailed description
Triple-negative breast cancer (TNBC) lack the expression of oestrogen receptor (ER), progesterone receptor(PR) and human epidermal growth factor receptor 2 (HER2) , and characterizes an aggressive behavior with higher risk of recurrence and death compared to other breast cancer subtypes. Little therapeutic progress has been made in adjuvant therapy in TNBC during the past decades and the standard of care is still missing.
Pre-clinical and clinical data suggest that platinum-based regimens represent an emerging therapeutic option for selected patients with homologous recombination repair deficiency (HRD). The HR system is critical in regulating and maintaining genome stability, and is one of the most commonly altered systems in TNBCs, up to 15-20% TNBC patients carry germline BRCA1/2 mutations. Other HR genes included PALB2, RAD51 etc. Tumors that harbor HRD possess an increased burden of genomic aberrations and lesions, and have been shown to have increased sensitivity to DNA crosslinking agents such as platinum salts. Platinum-based regimens have been encouraging in TNBC patients with HRD, given increases in both pathologic complete response (pCR) rates in neoadjuvant trials and objective response rates(ORR) in metastatic diseases. Further information are needed on how platinum-containing therapies affect long-term outcomes in the adjuvant setting.
In this trial, the investigators intend to compare the 3-year disease-free survival (DFS) of dose-dense epirubicin and cyclophosphamide followed by paclitaxel with paclitaxel plus carboplatin as adjuvant therapy in high-risk node-negative or node-positive TNBC patients with HRD. The other purpose of this trial is to observe the participants' tolerance.
- Conditions
- Triple Negative Breast Cancer
- Being tested
- Epirubicin, Cyclophosphamide, Paclitaxel, Carboplatin
- Keywords
- homologous recombination deficiency;adjuvant chemotherapy;anthracycline;taxanes;platinum
- Medical subject headings
- Triple Negative Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
EpirubicinDrug
Epirubicin 90mg/m2 iv d1 or divide into two days
CyclophosphamideDrug
cyclophosphamide600mg/m2 iv d1,q14d*4cycles;with G-CSF support: 3ug/kg ih
PaclitaxelDrug
paclitaxel 175mg/m2 iv d1, q14d*4cycles
CarboplatinDrug
carboplatin AUC=3 iv d2, q14d*8cycles;with G-CSF support: 3ug/kg ih
PaclitaxelDrug
paclitaxel 175mg/m2 iv d1, q14d*8cycles
| Study group | Role | What they receive |
|---|---|---|
| AC-T(dose-dense) | Active comparator | A: epirubicin, pharmorubicin (EPI) C: cyclophosphamide (CTX） T: paclitaxel (PTX） Receives: Drug: Epirubicin; Drug: Cyclophosphamide; Drug: Paclitaxel |
| TP(dose-dense) | Experimental | T: paclitaxel (PTX） P: carboplatin (CBP) Receives: Drug: Carboplatin; Drug: Paclitaxel |
What is being measured
The primary outcome is the main question the study is designed to answer.
3-year disease-free survival
The participants will be followed by the telephone for the duration, an expected average of 3 years.
Measured: Three years
Secondary outcomes (1)
Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]
Incidence of neutropenic fever; Incidence of grade 3-4 side effects; Toxicity assessed by NCI CTCAE v5.0
Measured: Three years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Mar 2019
- Study start22 Feb 2019
- Primary completionFeb 2024 (estimated)
- Study completionDec 2024 (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.
- 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 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 200 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Chinese Academy of Medical Sciences
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Binghe Xu, Chinese Academy of Medical Sciences
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03876886
- Sponsor's protocol ID
- BXu-1839
- Status last verified
- Mar 2019
- First submitted
- 14 Mar 2019
- Last updated
- 21 Mar 2019
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 21 Mar 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Randomized Phase Ⅲ Trial Comparing Dose-dense Epirubicin and Cyclophosphamide Followed by Paclitaxel With Paclitaxel Plus Carboplatin as Adjuvant Therapy for Triple-negative Breast Cancer With Homologous Recombination Repair Deficiency
- ClinicalTrials.gov ID
- NCT03876886
- Acronym / sponsor ID
- BXu-1839
- Conditions
- Triple Negative Breast Cancer
- Keywords
- homologous recombination deficiency;adjuvant chemotherapy;anthracycline;taxanes;platinum
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 200 participants (estimated)
- Lead sponsor
- Chinese Academy of Medical SciencesUniversity, hospital or other
- Study start
- 22 Feb 2019 (actual)
- Primary completion
- Feb 2024 (estimated)
- Study completion
- Dec 2024 (estimated)
- First posted
- 15 Mar 2019 (actual)
- 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.
The purpose of this trial is to compare the 3-year disease-free survival of dose-dense epirubicin and cyclophosphamide followed by paclitaxel with paclitaxel plus carboplatin as adjuvant therapy for triple-negative breast cancer with homologous recombination repair deficiency.
The other purpose of this trial is to observe the patient's tolerance.
Detailed description
Triple-negative breast cancer (TNBC) lack the expression of oestrogen receptor (ER), progesterone receptor(PR) and human epidermal growth factor receptor 2 (HER2) , and characterizes an aggressive behavior with higher risk of recurrence and death compared to other breast cancer subtypes. Little therapeutic progress has been made in adjuvant therapy in TNBC during the past decades and the standard of care is still missing.
Pre-clinical and clinical data suggest that platinum-based regimens represent an emerging therapeutic option for selected patients with homologous recombination repair deficiency (HRD). The HR system is critical in regulating and maintaining genome stability, and is one of the most commonly altered systems in TNBCs, up to 15-20% TNBC patients carry germline BRCA1/2 mutations. Other HR genes included PALB2, RAD51 etc. Tumors that harbor HRD possess an increased burden of genomic aberrations and lesions, and have been shown to have increased sensitivity to DNA crosslinking agents such as platinum salts. Platinum-based regimens have been encouraging in TNBC patients with HRD, given increases in both pathologic complete response (pCR) rates in neoadjuvant trials and objective response rates(ORR) in metastatic diseases. Further information are needed on how platinum-containing therapies affect long-term outcomes in the adjuvant setting.
In this trial, the investigators intend to compare the 3-year disease-free survival (DFS) of dose-dense epirubicin and cyclophosphamide followed by paclitaxel with paclitaxel plus carboplatin as adjuvant therapy in high-risk node-negative or node-positive TNBC patients with HRD. The other purpose of this trial is to observe the participants' tolerance.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| AC-T(dose-dense) | Active comparator | Drug: Epirubicin, Drug: Cyclophosphamide, Drug: PaclitaxelA: epirubicin, pharmorubicin (EPI) C: cyclophosphamide (CTX） T: paclitaxel (PTX） |
| TP(dose-dense) | Experimental | Drug: Carboplatin, Drug: PaclitaxelT: paclitaxel (PTX） P: carboplatin (CBP) |
Who may qualify
- Ages
- 18 to 60 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (10 listed)
- 18-60 years
- Histologically confirmed adenocarcinoma of the breast, complete tumor removal by either modified radical mastectomy or local excision plus axillary lymph node dissection (i.e., breast conservation therapy) or sentinel node biopsy. (Tumor-free margins at least 1 mm for both invasive and noninvasive carcinoma except for lobular carcinoma in situ (less than 1 mm allowed);
- Histologically confirmed ER(-) PR(-) and HER-2(IHC(immunohistochemistry) 0-1+ or FISH (fluorescence in situ hybridization) negative)
- Next-generation sequencing confirmed homologous recombination repair deficiency
- Meet one of the following criteria:
Key exclusion criteria (10 listed)
- Prior systemic treatment of breast cancer, including chemotherapy;
- Metastatic breast cancer;
- Patients with medical conditions that indicate intolerant to adjuvant therapy and related treatment, including uncontrolled pulmonary disease, diabetes mellitus, severe infection, active peptic ulcer, coagulation disorder, connective tissue disease or myelo-suppressive disease;
- Has active hepatitis B or hepatitis C with abnormal liver function tests (LFTs) or is known to be HIV positive;
- Contraindication for using dexamethasone;
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 |
|---|---|---|
| EpirubicinEpirubicin 90mg/m2 iv d1 or divide into two days | Drug | AC-T(dose-dense) |
| Cyclophosphamidecyclophosphamide600mg/m2 iv d1,q14d*4cycles;with G-CSF support: 3ug/kg ih | Drug | AC-T(dose-dense) |
| Paclitaxelpaclitaxel 175mg/m2 iv d1, q14d*4cycles | Drug | AC-T(dose-dense) |
| Carboplatincarboplatin AUC=3 iv d2, q14d*8cycles;with G-CSF support: 3ug/kg ih | Drug | TP(dose-dense) |
| Paclitaxelpaclitaxel 175mg/m2 iv d1, q14d*8cycles | Drug | TP(dose-dense) |
Primary outcome
3-year disease-free survival
Time frame: Three years
The participants will be followed by the telephone for the duration, an expected average of 3 years.
1 secondary outcome
Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]
Time frame: Three years
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Mar 2019.
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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.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Epirubicin, Cyclophosphamide and Paclitaxel in people with Triple Negative Breast Cancer, run by Chinese Academy of Medical Sciences at 1 site in China.
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 10 inclusion and 10 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 21 Mar 2019. 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 China. 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
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 Binghe Xu (+86-10-87788120, xubinghe@medmail.com.cn), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
3-year disease-free survival (time frame: Three 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 21 Mar 2019.