Tucidinostat Combined With Metronomic Capecitabine and Endocrine Therapy for Advanced HR-positive, HER2-negative Breast Cancer After CDK4/6 Inhibitor.

NCT05411380 | Unknown Phase 2

• 1 other identifier: SYSUCC-020
• Study Type: interventional
• Target: 73
• Locations: 1 country
• Sites: 1

Brief Summary

The study is designed to explore the clinical benefit following treatment with tucidinosta in combination with metronomic capecitabine and endocrine therapy in patients with hormone receptor-positive, Her2-negative advanced breast cancer who have received CDK4/6 Inhibitor treatment.

Conditions

Breast Cancer

Keywords

metronomic capecitabine; endocrine therapy; histone deacetylase inhibitor; metastatic breast cancer

Outcome Measures

Primary Outcomes (1)

• Objective Response Rate

  Objective response is defined as a complete response (CR) or partial response (PR) according to RECIST v.1.1 recorded from randomization until disease progression or death due to any cause

  Up to 3 years

Secondary Outcomes (3)

• Progress-free survival

  Up to 3 years

• Disease Control Rate

  Up to 3 years

• Overall Survival

  Up to 3 years

Study Arms (1)

Tucidinostat+Metronomic Capecitabine+Endocrine Therapy

EXPERIMENTAL

This arm is divided into two groups. The main difference of this two groups lies in the selection of endocrine therapy. One is supposed to choose aromatase inhibitor, and the other is fulvestrant. The principle of making choice is based on the history of endocrine drug use.

Drug: Tucidinostat; Drug: Capecitabine; Drug: Endocrine Therapy

Interventions

Tucidinostat DRUG

20mg each time, orally 30 minutes after dinner, 3 weeks for a cycle, administered on day 1, day 4, day 8, day 11, day 15,and day 18 of each cycle (twice a week, at least 3 days between each administration)

Also known as: Chidamide

Tucidinostat+Metronomic Capecitabine+Endocrine Therapy

Capecitabine DRUG

500mg orally three times a day (continuously)

Also known as: Xeloda

Tucidinostat+Metronomic Capecitabine+Endocrine Therapy

Endocrine Therapy DRUG

Anastrozole, 1mg, orally once daily or Letrozole, 2.5mg, orally once daily or Exemestane , 25mg, orally once daily or fulvestrant 500 mg each time, intramuscularly, injected on the 1st day and 15th day of the 1st cycle, and on the 1st day for subsequent cycle( 4 weeks for one cycle)

Also known as: Anastrozole, Letrozole, Exemestane, Fulvestrant

Tucidinostat+Metronomic Capecitabine+Endocrine Therapy

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• \. ≥18 years old, and ≤75 years old, female; 2. Histologically confirmed HR positive and HER2 negative postmenopausal metastatic breast cancer patients \[HER2 negative is defined as immunohistochemistry(IHC) 0 or IHC 1+, and if the score of IHC is 2+, fluorescence in situ hybridization technology (FISH) test must be negative, HR positve is defined as ER or PR ≥1%;\]; 3. After the failure of previous CDK4/6 inhibitor therapy; 4.Receive one line of chemotherapy at most; 5.Premenopausal women need to take effective measures to suppress ovarian function, such as drug suppression, oophorectomy; 6.ECOG score 0-1; 7. According to RECIST1.1 criteria, at least there is one measurable lesion or simple bone metastasis; 8. The main organ and bone marrow function levels meet the following requirements:
• Blood routine: neutrophil (ANC) ≥ 1.5×109/L; platelet count (PLT) ≥ 90× 109/L; hemoglobin (Hb) ≥ 90g/L; It is required that no blood products (including red blood cells and platelet products, etc.) have been transfused and no growth factors (including colony-stimulating factor, interleukin, and erythropoietin, etc.) have been used for supportive treatment within 2 weeks before the examination.
• Liver function: serum total bilirubin (TBIL) ≤ 1.5 × upper limit of normal (ULN); alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5 × ULN (with liver Requirements for metastatic patients: ALT and AST≤5×ULN);
• Renal function: serum creatinine (Cr)≤1.5×ULN or creatinine clearance rate\>60mL/min;
• \. Expected survival time ≥ 3 months; 10. Voluntary participation study, signed written informed consent.

You may not qualify if:

• Known hypersensitivity to any formulation component of the study drug;
• patients with previous severe, unexpected reactions to fluoropyrimidines or known hypersensitivity to fluoropyrimidines;
• Patients with complete deficiency of dihydropyrimidine dehydrogenase (DPD) activity;
• Visceral crisis;
• Previously received treatment with histone deacetylase inhibitors or fluoropyrimidine drugs such as capecitabine;
• Received chemotherapy, targeted therapy, Chinese herbal medicine with anti-tumor indications, or immunomodulatory drugs (including thymosin, interferon, interleukin, etc.) within 4 weeks before enrollment, or still within 5 half-lives of such drugs;
• Received palliative radiotherapy for local lesions within 4 weeks before enrollment;
• Patients with gastrointestinal perforation, fistula, abdominal abscess, gastrointestinal ulcer or active diverticulosis before enrollment;
• Significant malnutrition (weight loss \> 5% in the past 1 month or \> 15% in the past 3 months, or food intake decreased by 1/2 or more in the past week), or still need to rely on intravenous nutritional support during the screening period;
• Toxicities that did not recover to National Cancer Institute Common Adverse Event Terminology Version 5.0 (NCICTCAEv5.0) grade 0 or 1 toxicity from prior antineoplastic therapy prior to the first dose of study treatment(alopecia, grade 2 fatigue, grade 2 anemia, non-clinically critical and asymptomatic laboratory abnormalities can be enrolled);
• Patients with currently symptomatic brain or meningeal metastasis;
• Received immunosuppressive drugs within 4 weeks before enrollment, excluding nasal spray, inhalation or other local glucocorticoids or physiological doses systemic glucocorticoids (no more than 10 mg/day of prednisone or other glucocorticoids at an equivalent dose), or use of glucocorticoids for the prevention of contrast medium allergy;
• The patient has any active autoimmune disease or has history of immune disorders (including but not limited to: interstitial pneumonia, uveitis, enteritis, hepatitis, hypophysitis, nephritis, hyperthyroidism, hypothyroidism; patients with vitiligo or complete remission of asthma in childhood without any intervention in adulthood can be included; those with asthma that require medical intervention with bronchodilators are not included);
• Patients with active pulmonary tuberculosis who are receiving anti-tuberculosis treatment or have received anti-tuberculosis treatment within 1 year before screening;
• Complications requiring long-term use of immunosuppressive drugs, or systemic or topical use of corticosteroids with immunosuppressive doses;

Sponsors & Collaborators

• wang shusen: lead

Study Sites (1)

Shusen Wang

Guangzhou, Gangdong, China

RECRUITING

MeSH Terms

Conditions

Breast Neoplasms

Interventions

N-(2-amino-5-fluorobenzyl)-4-(N-(pyridine-3-acrylyl)aminomethyl)benzamide; Capecitabine; Anastrozole; Letrozole; exemestane; Fulvestrant

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Fluorouracil; Uracil; Pyrimidinones; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Nitriles; Organic Chemicals; Triazoles; Azoles; Estradiol; Estrenes; Estranes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Estradiol Congeners; Gonadal Steroid Hormones; Gonadal Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists

Study Officials

• Susen Wang, MD

  Sun Yat-sen University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Susen Wang, MD

CONTACT

+86-13926168469; wangshs@sysucc.org.cn

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Chief Physician

Study Record Dates

• First Submitted: June 5, 2022
• First Posted: June 9, 2022
• Study Start: October 3, 2022
• Primary Completion: April 1, 2024
• Study Completion: April 1, 2025
• Last Updated: November 4, 2022

Record last verified: 2022-11

Locations

CN (1)