Neoplasms

Skin and Connective Tissue Diseases

All Conditions

Rare Diseases

Breast Neoplasms

Breast Diseases

Skin Diseases

Myotonic Dystrophy Type 1

Antineoplastic Agents

All Drugs and Chemicals

Anti-Arrhythmia Agents

Vasodilator Agents

Analgesics

Ado-Trastuzumab Emtansine

Trastuzumab

Trastuzumab deruxtecan

Adenosine

Antineoplastic Agents, Immunological

Tubulin Modulators

Antimitotic Agents

Immunotoxins

Immunoconjugates

Immunologic Factors

Participants who will be randomized to receive trastuzumab deruxtecan (T-DXd) at a starting dose of 5.4 mg/kg.

Participants who will be randomized to receive trastuzumab ematansine (T-DM1) at a starting dose of 3.6 mg/kg.

Administered initially as an intravenous (IV) infusion at a dose of 5.4 mg/kg on Day 1 of each 21-day cycle

DS-8201a

Administered initially as an intravenous (IV) infusion at a dose of 3.6 mg/kg on Day 1 of each 21-day cycle

T-DM1

Global Clinical Leader

Patients with HER2-positive primary breast cancer (BC) who do not achieve complete response after appropriate neoadjuvant therapy are at higher risk of disease recurrence. More effective treatment options are needed for this patient population. This study will examine the efficacy and safety of trastuzumab deruxtecan (T-DXd) compared with trastuzumab emtansine (T-DM1) in high-risk patients with residual invasive breast cancer following neoadjuvant therapy.

This study will examine trastuzumab deruxtecan (T-DXd) versus trastuzumab emtansine (T-DM1) in patients with HER2-positive primary BC who have residual invasive disease in breast or axillary lymph nodes with higher risk of recurrence, which includes patients who were inoperable at disease presentation or had pathological node-positive status after neoadjuvant therapy.

The primary objective is to compare invasive disease-free survival (IDFS) between T-DXd and T-DM1 treatment arms in this population. The key secondary objective of the study is to evaluate disease-free survival (DFS).

A Study of Trastuzumab Deruxtecan (T-DXd) Versus Trastuzumab Emtansine (T-DM1) in High-risk HER2-positive Participants With Residual Invasive Breast Cancer Following Neoadjuvant Therapy (DESTINY-Breast05)

A Phase 3, Multicenter, Randomized, Open-Label, Active-Controlled Study of Trastuzumab Deruxtecan (T-DXd) Versus Trastuzumab Emtansine (T-DM1) in Participants With High-Risk HER2-Positive Primary Breast Cancer Who Have Residual Invasive Disease in Breast or Axillary Lymph Nodes Following Neoadjuvant Therapy (DESTINY-Breast05)

De-identified individual participant data (IPD) on completed studies and applicable supporting clinical trial documents may be available upon request at https://vivli.org/. In cases where clinical trial data and supporting documents are provided pursuant to our company policies and procedures, Daiichi Sankyo will continue to protect the privacy of our clinical trial participants. Details on data sharing criteria and the procedure for requesting access can be found at this web address: https://vivli.org/ourmember/daiichi-sankyo/

AstraZeneca

NSABP Foundation Inc

German Breast Group

Spanish Breast Cancer Research Group (SOLTI)

Daiichi Sankyo

Capecitabine

Entinostat

Antimetabolites

Histone Deacetylase Inhibitors

Enzyme Inhibitors

Dose escalation of the combination of entinostat and capecitabine in MBC patients. This dose will be given to MBC patients and to BC patients with residual invasive disease after neoadjuvant chemotherapy and surgery.

The dose combinations include:

Combination 1: 3 mg/week entinostat, 800 mg/m2 twice a day for 14 days of capecitabine Combination 2: 5 mg/week entinostat, 800 mg/m2 twice a day for 14 days of capecitabine Combination 3: 3 mg/week entinostat, 1000 mg/m2 twice a day for 14 days of capecitabine Combination 4: 5 mg/week entinostat, 1000 mg/m2 twice a day for 14 days of capecitabine

If a participant experiences unacceptable side effects, he or she will receive the next lowest dose combination. If he or she is on Combination 1, he or she will stop study treatment.

In metastatic breast cancer patients, entinostat will be taken orally starting at 3 mg per week and will increase to 5 mg per week in the absence of unacceptable side effects. The safe dose (when combined with capecitabine) will be confirmed in additional metastatic breast cancer patients and breast cancer patients with residual invasive disease following neoadjuvant chemotherapy and surgery.

In metastatic breast cancer patients, capecitabine will be taken by mouth starting at 800 mg/m2 twice a day for 14 days per cycle and increase to 1000 mg/m2 (for 14 days per cycle) in the absence of unacceptable side effects. The safe dose (when combined with capecitabine) will be confirmed in additional metastatic breast cancer patients and breast cancer patients with residual invasive disease following neoadjuvant chemotherapy and surgery.

Patrick Dillon, MD

The purpose of this study is to learn about the safety and side effects of combining entinostat, an investigational drug, with capecitabine, a drug commonly used in breast cancer (BC), in both participants with metastatic breast cancer (MBC) and then participants with high-risk breast cancer after neo-adjuvant therapy.

In order to identify the maximum dose that should be used in future participants, the first participants will start at a low dose of both drugs. If the participants on this dose level tolerate the treatment well without too many side effects, the next participants will receive a higher dose of one of the medications, and if those participants also tolerate the treatment well, then the drugs will continue to be increased with the next participants until a maximum dose that participants tolerate well is reached.

Participants in both groups will receive entinostat on days 1, 8, and 15 of each 21-day cycle and capecitabine on days 1-14 of each cycle. MBC participants may receive this treatment as long as they do not have disease progression or side effects that require them to stop study treatment while participants with high-risk BC after neo-adjuvant therapy will receive up to 8 cycles of study treatment as long as they do not have disease progression or side effects that require them to stop study treatment.

While participants are on study treatment, they will have regular physical exams and labs. After participants finish study treatment, they should be followed by their primary oncologist at least once a year. Study staff will also be in contact by phone at least once a year for 10 years.

A Pilot Study of the Combination of Entinostat With Capecitabine in High Risk Breast Cancer After Neo-adjuvant Therapy

Participants will be followed annually following completion of study treatment

For participants with high risk BC after neo-adjuvant therapy, blood will be collected prior to treatment and at end of treatment and tested for levels of circulating tumor DNA. This will be used to describe the relationship between circulating tumor DNA and residual disease at the time of surgery.

For participants with high risk BC after neo-adjuvant therapy, blood will be collected prior to treatment and at end of treatment and tested for levels of circulating tumor cells. This will be used to describe the relationship between circulating tumor cells and residual disease at the time of surgery.

For participants with high risk BC after neo-adjuvant therapy, blood will be collected prior to treatment and at end of treatment and tested for levels of circulating tumor DNA. This will be used to describe any changes in the levels prior to and following treatment.

For participants with high risk BC after neo-adjuvant therapy, blood will be collected prior to treatment and at end of treatment and tested for levels of circulating tumor DNA. This will be used to describe the relationship between circulating tumor DNA and disease-free survival.

For participants with high risk BC after neo-adjuvant therapy, blood will be collected prior to treatment and at end of treatment and tested for levels of circulating tumor cells. This will be used to describe the relationship between circulating tumor cells and disease-free survival.

This will be defined based on the number of "dose limiting toxicities" in participants at each dose level.

Frequency of adverse events (AEs) in participants with high-risk BC after neo-adjuvant therapy at the determined MTDC.

Severity of adverse events (AEs) in participants with high-risk BC after neo-adjuvant therapy at the determined MTDC.

Adverse events (AEs) will be assessed via the Common Terminology Criteria for Adverse Events (CTCAE) version 4.03 in MBC participants at the determined MTDC.

Disease-free survival (DFS) following combination therapy with entinostat and capecitabine

Adverse events (AEs) will be graded via the CTCAE version 4.03 in MBC participants at the determined MTDC.

Adverse events (AEs) will be assessed via the CTCAE version 4.03 in participants on both arms of the study at the determined MTDC.

Adverse events (AEs) will be graded via the CTCAE version 4.03 in participants on both arms of the study at the determined MTDC.

Syndax Pharmaceuticals

University of Virginia

Principal Investigator

Triple Negative Breast Neoplasms

Antirheumatic Agents

Anti-Infective Agents

Cyclophosphamide

Epirubicin

Taxane

Pirarubicin

Immunosuppressive Agents

Antineoplastic Agents, Alkylating

Alkylating Agents

Anti-Bacterial Agents

Antibiotics, Antitubercular

Adjuvant chemotherapy for triple negative breast cancer with residual invasive disease (invasive breast tumor size≥1cm and/or positive axillary lymph nodes) after taxanes and platinum based neoadjuvant chemotherapy.

Adjuvant chemotherapy regiments: Epirubicin 80-90mg/m2 IV or Pirarubicin 50mg/m2 IV + Cyclophosphamide 600mg/m2 IV, q21d\*4cycles.

No adjuvant chemotherapy for triple negative breast cancer with residual invasive disease (invasive breast tumor size≥1cm and/or positive axillary lymph nodes) after taxanes and platinum based neoadjuvant chemotherapy.

Epirubicin 80-90mg/m2 IV or Pirarubicin 50mg/m2 IV, q21d\*4cycls

Epirubicin or Pirarubicin

Cyclophosphamide 600mg/m2 IV, q21d\*4cycls

Pin ZHANG, MD

This study will evaluate the efficacy and safety of antharcycline-based adjuvant chemotherapy compared with observation in triple negative breast cancer (TNBC) patients with residual invasive disease after platinum and taxanes based neoadjuvant chemotherapy.

This study is a multi-center, randomized, phase II study. TNBC patients with residual invasive disease (invasive breast tumor size≥1cm and/or positive axillary lymph nodes) after platinum and taxanes based neoadjuvant chemotherapy are enrolled (n = 286). Patients are assigned to the chemotherapy group or the observation group at a 1:1 ratio randomly 4-6 weeks after surgery. Patients in the chemotherapy group are given anthracycline combined with cyclophosphamide regimen for 4 cycles. At the same time, the blood and tissue samples are collected for relevant tests. Follow up every 3-6 months and record recurrences and deaths.

Adjuvant Chemotherapy for Triple Negative Breast Cancer Patients With Residual Disease After Neoadjuvant Chemotherapy

A Multicenter, Randomised, Open-label Phase II Study to Evaluate the Efficacy and Safety of Adjuvant Chemotherapy for Triple Negative Breast Cancer Patients With Residual Disease After Platinum-based Neoadjuvant Chemotherapy

RFS defined as the time from randomization to the first recurrence event or death through the end of study

OS defined as the time from randomization to all-cause death through the end of study

To assess the toxicity of adjuvant chemotherapy by CTCAE v5.0

To assess the mean changes from baseline score in patient-reported quality of life using EORTC QLQ-C30

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
A Study of Trastuzumab Deruxtecan (T-DXd) Versus Trastuzumab Emtansine (T-DM1) in High-risk HER2-positive Participants With Residual Invasive Breast Cancer Following Neoadjuvant Therapy (DESTINY-Breast05)	NCT04622319	HER2-Positive P... Residual Invasi...	DS-8201a T-DM1	18 Years -	Daiichi Sankyo
A Pilot Study of the Combination of Entinostat With Capecitabine in High Risk Breast Cancer After Neo-adjuvant Therapy	NCT03473639	Metastatic Brea... Breast Cancer	Entinostat Capecitabine	18 Years -	University of Virginia
A Pilot Study of the Combination of Entinostat With Capecitabine in High Risk Breast Cancer After Neo-adjuvant Therapy	NCT03473639	Metastatic Brea... Breast Cancer	Entinostat Capecitabine	18 Years -	University of Virginia
Adjuvant Chemotherapy for Triple Negative Breast Cancer Patients With Residual Disease After Neoadjuvant Chemotherapy	NCT04437160	Triple Negative...	Epirubicin or P... Cyclophosphamid...	18 Years - 75 Years	ChineseAMS

Spots Global Cancer Trial Database for residual invasive breast cancer