Neoadjuvant Therapy Study Guided by Drug Screening in Vitro for Human Epidermal Growth Factor Receptor 2 (HER2) Negative Early Breast Cancer Patients

Neoadjuvant Therapy Study Guided by Drug Screening in Vitro Patient-derived Tumor-like Cell Clusters for Human Epidermal Growth Factor Receptor 2 (HER2) Negative Early Breast Cancer Patients

Neoadjuvant treatment is an important treatment for early breast cancer patients. Patients with triple negative subtype who achieved pCR after neoadjuvant treatment would have longer survival. The neoadjuvant treatment for her2 negative patient was chemotherapy with combined drugs. However, not all patients benefit from chemotherapy but suffer from chemotherapy-related side effects. It was unknown for a patient who could benefit from which drug before chemotherapy. Drug sensitivity screening in vitro was a promising method for choosing chemotherapy. But there was no method could select effective drugs accurately for breast cancer patients until now.

Previously, investigators developed a patient-derived tumor-like cell clusters in vitro culture technology. Feasibility for guiding clinical treatment by drug sensitivity screening based on this technology have been explored by preliminary exploration with a well corresponding. And the results have been published. This study will explore whether drug screening in vitro patient-derived tumor-like cell clusters from breast cancer tissue could be a method for selection of chemotherapy for her2 negative participants.

Study Overview

• Status: Recruiting
• Conditions: HER2-negative Early Breast Cancer
• Intervention / Treatment: Drug: neoadjuvant chemotherapy upon in vitro PTC drug sensitivity screening for triple negative breast cancer; Drug: neoadjuvant chemotherapy upon in vitro PTC drug sensitivity screening for luminal like breast cancer

Detailed Description

Neoadjuvant chemotherapy for breast cancer could make unresectable breast cancer be resectable and improve breast conservation rate. Patients with triple negative subtype who achieved pCR after neoadjuvant treatment would have longer survival. The neoadjuvant treatment for her2 negative patient was chemotherapy with combined drugs. However, not all patients benefit from chemotherapy but suffer from chemotherapy-related side effects. It was unknown for a patient who could benefit from which drug before chemotherapy. Drug sensitivity screening in vitro was a promising method for choosing chemotherapy. But there was no method could select effective drugs accurately for breast cancer participants until now.

Previously, investigators developed a patient-derived tumor-like cell clusters (PTC) in vitro culture technology. It is a cell cluster including tumor cells, mesenchymal cells and lymphocytes, which simulates the tumor microenvironment in vitro. In the preliminary exploration, investigators included 35 early breast cancer participants, the corresponding between in vitro drug sensitivity screening based on this technology and clinical treatment results was well. The results have been published.

This study will focus on her2 negative early breast cancer participants. 46 participants will be included. All of them will received in vitro drug sensitivity screening upon PTC before neoadjuvant therapy. The choice of chemotherapy drugs is determined based on the PTC drug sensitivity results. If single-agent chemotherapy is effective in vitro, this drug will be the chemotherapy regimen for the corresponding participants.

• Study Type: Interventional
• Enrollment (Anticipated): 46
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Chaobin Wang, doctor; Phone Number: +86-10-8832-4010; Email: hzwcb1990@163.com

Study Locations

• China
  • Beijing, China
    • Recruiting
    • Peking University People's Hospital
    • Contact: Chaobin Wang, doctor; Phone Number: +86-10-88324010; Email: hzwcb1990@163.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• invasive breast cancer
• HER2 negative
• T2 or node positive
• Eastern Cooperative Oncology Group(ECOG) 0-1

Exclusion Criteria:

• stage IV
• inflammatory breast cancer
• Severe chronic disease

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Neoadjuvant therapy base on PTC drug screening for triple negative early breast cancer; Patients with triple negative subtype will receive neoadjuvant chemotherapy based on PTC drug screening.	Drug: neoadjuvant chemotherapy upon in vitro PTC drug sensitivity screening for triple negative breast cancer; The choice of chemotherapy is based on the PTC drug sensitivity results.; Other Names: docetaxel and carboplatin; docetaxel and epirubicin
Experimental: Neoadjuvant therapy base on PTC drug screening for luminal like early breast cancer; Patients with luminal like subtype will receive neoadjuvant chemotherapy based on PTC drug screening.	Drug: neoadjuvant chemotherapy upon in vitro PTC drug sensitivity screening for luminal like breast cancer; The choice of chemotherapy is based on the PTC drug sensitivity results.; Other Names: docetaxel and epirubicin; docetaxel and cyclophosphamide; epirubicin and cyclophosphamide

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
pathological complete response(pCR)	ypT0/is, ypN0	up to 24 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
event-free survival (EFS)	The time from random assignment to disease progression, including local progression before surgery; disease recurrence-local, regional, distant, ipsilateral noninvasive, or contralateral (invasive or noninvasive)-or death from any cause	5 years
invasive disease-free survival (IDFS)	The time from surgery to the first documented occurrence of an event defined as ipsilateral invasive local recurrence, ipsilateral locoregional invasive recurrence, distant recurrence, contralateral invasive breast cancer, or death from any cause	5 years
objective response rate	complete response and partial response	up to 24 weeks

Collaborators and Investigators

• Sponsor: Peking University People's Hospital
• Investigators: Principal Investigator: Shu Wang, doctor, Peking University People's Hospital

Study record dates

Study Major Dates

• Study Start (Actual): April 2, 2021
• Primary Completion (Anticipated): June 30, 2022
• Study Completion (Anticipated): December 31, 2026

Study Registration Dates

• First Submitted: March 28, 2021
• First Submitted That Met QC Criteria: April 5, 2021
• First Posted (Actual): April 8, 2021

Study Record Updates

• Last Update Posted (Actual): April 6, 2022
• Last Update Submitted That Met QC Criteria: March 27, 2022
• Last Verified: March 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Enzyme Inhibitors; Excitatory Amino Acid Antagonists; Excitatory Amino Acid Agents; Antirheumatic Agents; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Alkylating; Alkylating Agents; Myeloablative Agonists; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Hypnotics and Sedatives; GABA Modulators; GABA Agents; Anticonvulsants; Antibiotics, Antineoplastic; Cytochrome P-450 Enzyme Inducers; Cytochrome P-450 CYP3A Inducers; Cytochrome P-450 CYP2B6 Inducers; Docetaxel; Cyclophosphamide; Carboplatin; Epirubicin; Phenobarbital
• Other Study ID Numbers: PekingUPH10B004

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No