HER2-negative Breast CancerPhase 2NCT04499118
AT Versus TP as Neoadjuvant Chemotherapy in Patients With HER2-negative Early Breast Cancer
A Phase 2 study testing AT regimen and TP regimen in people with HER2-negative Breast Cancer, run by Sichuan Provincial People's Hospital at 1 site in China.
Trial summary
This is a prospective, randomized and open-label phase II study, evaluating the efficacy and safety of AT vs TP regimen as neoadjuvant treatment for early HER2-negative breast cancer. Participants will undergo/receive HRD testing after enrollment. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- HER2-negative Breast Cancer
- What is being tested?
- AT regimen and TP regimen
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 100 participants
- Where
- 1 siteChina
- Study dates
- Aug 2020to Aug 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Written informed consent for all study specific procedures according to local regulatory requirements prior to beginning specific protocol procedures.
- Age ≥ 18 years.
- Male or female patients
- ECOG performance status ≤1
- Histologically confirmed invasive breast cancer by core needle or incisional biopsy (excisional biopsy is not allowed). Clinical stage T2-3 N0-2 or T1 N1-2 by physical exam or radiologic studies. In case of bilateral cancer, the investigator has to decide prospectively which side will be evaluated for the primary endpoint.
- Centrally confirmed negative HER2-status. Centrally confirmed estrogen and progesterone receptor, and Ki-67 status detected on core biopsy. ER/PR positive is defined as ≥1% stained cells and HER2-positive is defined as IHC 3+ or in-situ hybridisation (ISH) ratio ≥2.0.
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- Provide Formalin-fixed, paraffin-embedded (FFPE) breast tissue to take Homologous Recombinant Deficiency test.
- Tumor lesion in the breast with a palpable size of > 2 cm or a sonographical size of >1 cm in maximum diameter. If the tumor is not detectable with sonography mammography assessment can be considered. The lesion has to be measurable in two dimensions, preferably by sonography. In case of inflammatory disease, the extent of inflammation can be used as measurable lesion.
- Normal cardiac function must be confirmed by ECG and cardiac ultrasound (LVEF or shortening fraction) within 3 months prior to randomization. Results must be above the normal limit of the institution.
- Laboratory requirements:
- Hematology b) Absolute neutrophil count (ANC) ≥2.0 x 109 / L and c) Platelets ≥100 x 109 / L and d) Hemoglobin ≥10 g/dL (≥ 6.2 mmol/L) Hepatic function e) Total bilirubin ≥1.5x UNL and f) ASAT (SGOT) and ALAT (SGPT) ≥1.5x UNL and g) Alkaline phosphatase ≥2.5x UNL.
- Negative pregnancy test (urine or serum) within 14 days prior to randomization for all women of childbearing potential.
- Patients with a prior history of contra-lateral breast cancer are eligible if they have no evidence of recurrence of their initial primary breast cancer within the last 5 years.
- Individuals with a history of other malignancies are eligible if they have been disease-free for at least 5 years and are deemed by the investigator to be at low risk for recurrence of that malignancy and did not receive prior chemotherapy. Individuals with the following cancers are eligible if diagnosed and treated within the past 5 years: cervical cancer in situ, and basal cell or squamous cell carcinoma of the skin.
- Patients must be available and compliant for central diagnostics, treatment and follow-up.
- Patient must be willing to undergo mandatory research biopsy and blood draw. Prior to biopsy procedures patients must be able to be off medications that could increase the risk of bleeding
Who cannot join
- Prior chemotherapy for any malignancy within 3 years.
- Any prior treatment for the current breast cancer, including chemotherapy, hormonal therapy, radiation or experimental therapy.
- Ongoing use of any other investigational or study agents.
- Previous malignant disease without being disease-free for less than 5 years (except CIS of the cervix and non-melanomatous skin cancer).
- Renal dysfunction for which exposure to cisplatin would be unsafe or require cisplatin dose modification (i.e., Cre > 1.5 mg/dl or GFR < 60 cc/min).
- Inadequate general condition (not fit for anthracycline-taxane-targeted agents-based chemotherapy).
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- Evidence of metastasis before randomization
- Known human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS) related diseases, active or symptomatic viral hepatitis or chronic liver disease
- Known history of heart disease, for example: myocardial infarction or symptomatic cardiac ischemia within 24 weeks before screening; congestive heart failure; randomized history of clinically significant ventricular arrhythmias within the previous year; Mobitz II level 2 Or a history of tertiary heart block, hypertension is uncontrolled
- History of significant neurological or psychiatric disorders including psychotic disorders, dementia or seizures that would prohibit the understanding and giving of informed consent.
- Have undergone major surgery within 14 days before entering the study
- Any other reason the investigator considers inappropriate to participate in this clinical trial
Trial locations and contacts
1 site in 1 country.
China1 site
Department of breast surgery, Sichuan Provincial People's Hospital
Chengdu, Sichuan, 610031
About this study
Official title: A Randomized Phase 2 Trial to Assess the Efficacy of AT in Comparison to TP as Neoadjuvant Chemotherapy in Patients With HER2-negative Early Breast Cancer : Evaluating the Homologous Recombination Deficiency(HRD) Biomarker
This is a prospective, randomized and open-label phase II study, evaluating the efficacy and safety of AT vs TP regimen as neoadjuvant treatment for early HER2-negative breast cancer. Participants will undergo/receive HRD testing after enrollment. HRD-positive patients will be randomly assigned in a ratio of 1:1 to receive AT（Doxorubicin or Epirubicin+docetaxel）or TP（Albumin paclitaxel + Cisplatin or Carboplatin）regimen respectively, followed by surgery. HRD-negative patients will be assigned to receive TP（Albumin paclitaxel + Cisplatin or Carboplatin）regimen if TNBC, or AT（Doxorubicin or Epirubicin+docetaxel）rigemen, followed by surgery.
Read the detailed description
This study intends to adopt Simon's two-stage optimal design. In stage 1, 15 HRD-positive and 15 HRD-negative patients will be recruited to receive AT or TP regimen as neoadjuvant therapy. If more than 5 patients in the HRD-positive group achieve pCR(pathological complete response) , the trial expands to stage 2, otherwise the trial terminates. In stage 2, another 31 HRD- positive and 31 HRD-negative patients will be enrolled.
- Conditions
- HER2-negative Breast Cancer
- Being tested
- AT regimen, TP regimen
- Keywords
- Breast neoplasms, HER2-, Homologous Recombination Deficiency
- Medical subject headings
- Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AT regimenDrug
Also called Anthracycline/Paclitaxel
Doxorubin 60mg/㎡ d1 or Epirubicin 75mg/㎡ d1 Docetaxel 75mg/㎡ d1 1/21d
TP regimenDrug
Also called Paclitaxel/Platinum
Albumin paclitaxel 125mg/㎡ d1, 8 Cisplatin 75mg/㎡ d1-3 1/21d✖6 or carboplatin AUC6 d1 1/21d✖6
| Study group | Role | What they receive |
|---|---|---|
| Arm a(HR+/HER2-,HRD-） | Experimental | Participants receive AT regimen for neoadjuvant therapy Receives: Drug: AT regimen |
| Arm b(TNBC, HRD-) | Experimental | Participants receive TP regimen for neoadjuvant therapy Receives: Drug: TP regimen |
| Arm c(HER2-,HRD+) | Experimental | Participants receive AT regimen for neoadjuvant therapy Receives: Drug: AT regimen |
| Arm d(HER2-, HRD+) | Experimental | Participants receive TP regimen for neoadjuvant therapy Receives: Drug: TP regimen |
What is being measured
The primary outcome is the main question the study is designed to answer.
Complete pathological response of breast and lymph nodes (ypT0/is ypN0; defined as no microscopic evidence of residual invasive viable tumor cells in all resected specimens of the breast and axilla)
- To compare the pathologic response to neoadjuvant AT regimen in HER2- breast cancer with and without HR-deficiency, defined as a high HRD score or a BRCA mutation
- To compare the pathologic response to neoadjuvant TP regimen in HER2- breast cancer with and without HR-deficiency, defined as a high HRD score or a BRCA mutation
- To compare the pathologic response to neoadjuvant AT vs TP regimen in HER2- breast cancer with HR-deficiency, defined as a high HRD score or a BRCA mutation
Measured: 24 weeks
Secondary outcomes (3)
Imaging response
To determine the response rates of the breast tumor and axillary nodes based on imaging tests. (sonography, mammography, or MRI) after treatment.
Measured: 24 weeks
Residual cancer burden in patients with HRD
RCB in the breast tissue and the lymph node tissue will be performed after the completion of neoadjuvant systemic therapy.
Measured: up to 24 weeks
response by pCR in HRD high versus tBRCA
To assess the pCR rate in HRD high with vs without tBRCA mutation
Measured: 24 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Aug 2020
- Study startAug 2020 (estimated)
- Primary completionAug 2021 (estimated)
- Study completionAug 2021 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for HER2-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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 100 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Sichuan Provincial People's Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Luojing, Sichuan Provincial People's Hospital
- Investigators
- Prof. Luojing, Principal investigator, Sichuan Provincial People's Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04499118
- Sponsor's protocol ID
- BCHRD201
- Status last verified
- Jul 2020
- First submitted
- 28 Jul 2020
- Last updated
- 5 Aug 2020
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Tutt A, Tovey H, Cheang MCU, Kernaghan S, Kilburn L, Gazinska P, Owen J, Abraham J, Barrett S, Barrett-Lee P, Brown R, Chan S, Dowsett M, Flanagan JM, Fox L, Grigoriadis A, Gutin A, Harper-Wynne C, Hatton MQ, Hoadley KA, Parikh J, Parker P, Perou CM, Roylance R, Shah V, Shaw A, Smith IE, Timms KM, Wardley AM, Wilson G, Gillett C, Lanchbury JS, Ashworth A, Rahman N, Harries M, Ellis P, Pinder SE, Bliss JM. Carboplatin in BRCA1/2-mutated and triple-negative breast cancer BRCAness subgroups: the TNT Trial. Nat Med. 2018 May;24(5):628-637. doi: 10.1038/s41591-018-0009-7. Epub 2018 Apr 30.
PubMed 29713086
Study at a glance
From the registry record, last updated by the sponsor on 5 Aug 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized Phase 2 Trial to Assess the Efficacy of AT in Comparison to TP as Neoadjuvant Chemotherapy in Patients With HER2-negative Early Breast Cancer : Evaluating the Homologous Recombination Deficiency(HRD) Biomarker
- ClinicalTrials.gov ID
- NCT04499118
- Acronym / sponsor ID
- BCHRD201
- Conditions
- HER2-negative Breast Cancer
- Keywords
- Breast neoplasms, HER2-, Homologous Recombination Deficiency
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 100 participants (estimated)
- Lead sponsor
- Sichuan Provincial People's HospitalUniversity, hospital or other
- Study start
- Aug 2020 (estimated)
- Primary completion
- Aug 2021 (estimated)
- Study completion
- Aug 2021 (estimated)
- First posted
- 5 Aug 2020 (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.
This is a prospective, randomized and open-label phase II study, evaluating the efficacy and safety of AT vs TP regimen as neoadjuvant treatment for early HER2-negative breast cancer. Participants will undergo/receive HRD testing after enrollment. HRD-positive patients will be randomly assigned in a ratio of 1:1 to receive AT（Doxorubicin or Epirubicin+docetaxel）or TP（Albumin paclitaxel + Cisplatin or Carboplatin）regimen respectively, followed by surgery. HRD-negative patients will be assigned to receive TP（Albumin paclitaxel + Cisplatin or Carboplatin）regimen if TNBC, or AT（Doxorubicin or Epirubicin+docetaxel）rigemen, followed by surgery.
Detailed description
This study intends to adopt Simon's two-stage optimal design. In stage 1, 15 HRD-positive and 15 HRD-negative patients will be recruited to receive AT or TP regimen as neoadjuvant therapy. If more than 5 patients in the HRD-positive group achieve pCR(pathological complete response) , the trial expands to stage 2, otherwise the trial terminates. In stage 2, another 31 HRD- positive and 31 HRD-negative patients will be enrolled.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Arm a(HR+/HER2-,HRD-） | Experimental | Drug: AT regimenParticipants receive AT regimen for neoadjuvant therapy |
| Arm b(TNBC, HRD-) | Experimental | Drug: TP regimenParticipants receive TP regimen for neoadjuvant therapy |
| Arm c(HER2-,HRD+) | Experimental | Drug: AT regimenParticipants receive AT regimen for neoadjuvant therapy |
| Arm d(HER2-, HRD+) | Experimental | Drug: TP regimenParticipants receive TP regimen for neoadjuvant therapy |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (16 listed)
- Written informed consent for all study specific procedures according to local regulatory requirements prior to beginning specific protocol procedures.
- Age ≥ 18 years.
- Male or female patients
- ECOG performance status ≤1
- Histologically confirmed invasive breast cancer by core needle or incisional biopsy (excisional biopsy is not allowed). Clinical stage T2-3 N0-2 or T1 N1-2 by physical exam or radiologic studies. In case of bilateral cancer, the investigator has to decide prospectively which side will be evaluated for the primary endpoint.
Key exclusion criteria (12 listed)
- Prior chemotherapy for any malignancy within 3 years.
- Any prior treatment for the current breast cancer, including chemotherapy, hormonal therapy, radiation or experimental therapy.
- Ongoing use of any other investigational or study agents.
- Previous malignant disease without being disease-free for less than 5 years (except CIS of the cervix and non-melanomatous skin cancer).
- Renal dysfunction for which exposure to cisplatin would be unsafe or require cisplatin dose modification (i.e., Cre > 1.5 mg/dl or GFR < 60 cc/min).
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 |
|---|---|---|
| AT regimenAlso: Anthracycline/PaclitaxelDoxorubin 60mg/㎡ d1 or Epirubicin 75mg/㎡ d1 Docetaxel 75mg/㎡ d1 1/21d | Drug | Arm a(HR+/HER2-,HRD-）, Arm c(HER2-,HRD+) |
| TP regimenAlso: Paclitaxel/PlatinumAlbumin paclitaxel 125mg/㎡ d1, 8 Cisplatin 75mg/㎡ d1-3 1/21d✖6 or carboplatin AUC6 d1 1/21d✖6 | Drug | Arm b(TNBC, HRD-), Arm d(HER2-, HRD+) |
Primary outcome
Complete pathological response of breast and lymph nodes (ypT0/is ypN0; defined as no microscopic evidence of residual invasive viable tumor cells in all resected specimens of the breast and axilla)
Time frame: 24 weeks
1. To compare the pathologic response to neoadjuvant AT regimen in HER2- breast cancer with and without HR-deficiency, defined as a high HRD score or a BRCA mutation 2. To compare the pathologic response to neoadjuvant TP regimen in HER2- breast cancer with and without HR-deficiency, defined as a high HRD score or a BRCA mutation 3. To compare the pathologic response to neoadjuvant AT vs TP regimen in HER2- breast cancer with HR-deficiency, defined as a high HRD score or a BRCA mutation
3 secondary outcomes
Imaging response
Time frame: 24 weeks
Residual cancer burden in patients with HRD
Time frame: up to 24 weeks
response by pCR in HRD high versus tBRCA
Time frame: 24 weeks
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Aug 2020.
- Background: PubMed 29713086Tutt A, Tovey H, Cheang MCU, Kernaghan S, Kilburn L, Gazinska P, Owen J, Abraham J, Barrett S, Barrett-Lee P, Brown R, Chan S, Dowsett M, Flanagan JM, Fox L, Grigoriadis A, Gutin A, Harper-Wynne C, Hatton MQ, Hoadley KA, Parikh J, Parker P, Perou CM, Roylance R, Shah V, Shaw A, Smith IE, Timms KM, Wardley AM, Wilson G, Gillett C, Lanchbury JS, Ashworth A, Rahman N, Harries M, Ellis P, Pinder SE, Bliss JM. Carboplatin in BRCA1/2-mutated and triple-negative breast cancer BRCAness subgroups: the TNT Trial. Nat Med. 2018 May;24(5):628-637. doi: 10.1038/s41591-018-0009-7. Epub 2018 Apr 30.
- GeparOLA: paclitaxel+olaparib vs paclitaxel/carboplatin followed by epirubicin/cyclophosphamide in HER2-/HRD+ early breast cancerLink provided by the sponsor.
- 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.
Prof. Luojing principal investigator
Sichuan Provincial People's 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 AT regimen and TP regimen in people with HER2-negative Breast Cancer, run by Sichuan Provincial People's Hospital 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 16 inclusion and 12 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 5 Aug 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 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 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 Prof. Luojing (86-18981838521, luckyluojingyu@163.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Complete pathological response of breast and lymph nodes (ypT0/is ypN0; defined as no microscopic evidence of residual invasive viable tumor cells in all resected specimens of the breast and axilla) (time frame: 24 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04499118, which also lists 1 linked publication.
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 5 Aug 2020.