Exploration of Dalpiciclib + Chidamide in HR+/HER2- Advanced Breast Cancer After Failure of CDK4/6 Inhibitor: a Phase Ⅰb Study

NCT05586841 | Unknown Phase 1

• 1 other identifier: MA-BC-II-047
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

A phase 1B study to explore the maximum tolerated dose (MTD) of dalpiciclib + chidamide in HR+/HER2- advanced breast cancer after the failure of CDK4/6 inhibitor therapy

Conditions

HR+/HER2- Advanced Breast Cancer

Keywords

Dalpiciclib; Chidamide; Maximum Tolerated Dose; the failure of CDK4/6 inhibitor therapy

Outcome Measures

Primary Outcomes (1)

• Maximum Tolerated Dose (MTD) of Dalpiciclib + Chidamide

  Bayesian optimal interval (BOIN) design method will be used in this clinical trial to determine the maximum tolerated dose (MTD).

  2 Years

Secondary Outcomes (3)

• Objective response rate (ORR) of different dose groups

  2 Years

• Safety of different dose groups (incidence of treatment-related adverse events)

  AE recorded from infromed consent to 28 days after treatment completion

• PFS

  2 Years

Study Arms (1)

Dalpiciclib + Chidamide

EXPERIMENTAL

Dalpiciclib will be administered in a dose of 100 mg/d or 125 mg/d. Chidamide shall be designed in a dose of 25 mg/BIW or 20 mg/BIW

Drug: Dalpiciclib; Drug: Chidamide

Interventions

Dalpiciclib DRUG

Dalpiciclib: 100 mg/d or 125 mg/d, po., qd, administered on an empty stomach (fasting should be ensured at least 1 hour before and 1 hour after administration). The drug will be administered in a 28-day cycle, with continuously administration in the first 3 weeks (D1-21), and discontinuation in the fourth week (D22-28).

Also known as: SHR6390

Dalpiciclib + Chidamide

Chidamide DRUG

Chidamide: 25 mg/BIW or 20 mg/BIW, po., q2w. The interval between doses should not be less than 3 days (e.g. Monday and Thursday, Tuesday and Friday, Wednesday and Saturday, etc.), administered 30 minutes after meals

Dalpiciclib + Chidamide

Eligibility Criteria

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

You may qualify if:

• Subjects voluntarily participate in this study and sign the informed consent form
• Female, aged ≥ 18 years.
• ECOG PS score: 0-2 points.
• Expected survival ≥ 3 months.
• Regionally recurrent or metastatic disease with histologically or cytologically confirmed ER+ and/or PR+ (≥ 10%), HER2- breast cancer that is not suitable for definitive excision or radiation therapy.
• Previously received antitumor therapy: 1) previously received ≤1 line of chemotherapy for recurrent or metastatic breast cancer; 2) Disease recurrence and/or metastasis during or after treatment with Palbociclib or Abemaciclib or Ribociclib in the setting of (neo-)adjuvant therapy, or during treatment with palbociclib or Abemaciclib or Ribociclib in a metastatic setting or after disease progression; 3) No more than 3 lines of endocrine therapy have been previously received for recurrent or metastatic breast cancer. 4) Line number of previous chemotherapy ≤1 line
• At least one extracranial measurable lesion as defined by RECIST v1.1;
• The function of vital organs meets the requirements;
• Absolute neutrophil count ≥ 1.5 × 10\^9/L;
• Platelets ≥ 90 × 10\^9/L;
• Hemoglobin ≥ 90g/L;
• Total bilirubin (TBIL) ≤ 1.5 × ULN;
• ALT and AST ≤ 2.5 × ULN;
• Urea/blood urea nitrogen (BUN) and creatinine (Cr) ≤1.5×ULN;
• Left ventricular ejection fraction (LVEF) ≥ 50%;

You may not qualify if:

• Previously received treatment with histone deacetylase inhibitor (HDACi);
• Previously received Dalpiciclib;
• MRI or lumbar puncture confirmed leptomeningeal metastasis;
• Central nervous system metastasis is confirmed by imaging; The following conditions will be excluded: 1) asymptomatic brain metastases without immediate radiotherapy or surgery; 2) Previously received local treatment (radiotherapy or surgery) for brain metastases, stable for at least 4 weeks, and no symptomatic treatment (including glucocorticoids, mannitol, bevacizumab, etc.) for more than 2 weeks with clinical symptoms;
• The participants presented with visceral crisis (such as lymphangitis carcinomatosis, bone marrow replacement, leptomeningeal metastasis, diffuse liver metastasis with abnormal liver function), rapid disease progression, and that is not suitable for endocrine therapy;
• Participants had ascites, pleural effusion and pericardial effusion with clinical symptoms at baseline, which required drainage within 4 weeks before the first medication;
• Inability to swallow, intestinal obstruction, or other factors that affect medication administration and absorption;
• Subjects that are diagnosed with any other malignancy within 5 years prior to the study, excluding non-melanoma skin cancer treated with radical therapy, basal or squamous cell skin cancer or carcinoma in situ of the cervix and papillary thyroid.
• The subject has undergone major surgery or major trauma or is expected to undergo major surgery within 4 weeks before the start of treatment;
• A known history of allergy to the drug ingredient of this protocol;

Sponsors & Collaborators

• Beijing 302 Hospital: lead

Study Sites (1)

The Fifth Medical Center of PLA General Hospital

Beijing, Beijing Municipality, 100071, China

Location

MeSH Terms

Interventions

dalpiciclib; N-(2-amino-5-fluorobenzyl)-4-(N-(pyridine-3-acrylyl)aminomethyl)benzamide

Central Study Contacts

Jinmei Zhou, Doctor

CONTACT

+86-010-66947250; jinzhu2714@sina.com

Huiqiang Zhang, Doctor

CONTACT

+86-010-66947250; zhanghq1206@163.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 17, 2022
• First Posted: October 19, 2022
• Study Start: November 1, 2022
• Primary Completion: November 30, 2024
• Study Completion: November 30, 2025
• Last Updated: October 19, 2022

Record last verified: 2022-10

Locations

CN (1)