Overview

AT Versus TP as Neoadjuvant Chemotherapy in Patients With HER2-negative Early Breast Cancer

Status:
Not yet recruiting
Trial end date:
2021-08-01
Target enrollment:
0
Participant gender:
All
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. 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.
Phase:
Phase 2
Accepts Healthy Volunteers?
No
Details
Lead Sponsor:
Sichuan Provincial People's Hospital
Treatments:
Albumin-Bound Paclitaxel
Paclitaxel
Criteria
Inclusion Criteria:

- 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.

- 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:

i. 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

Exclusion Criteria:

- 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).

- 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