A Clinical Study of the Efficacy and Safety of Chidamide in Combination With Camrelizumab and Carboplatin or Capecitabine in the Second and Third Line Treatment of Relapsed/Metastatic Triple-negative Breast Cancer

NCT ID: NCT05438706

Last Updated: 2022-06-30

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE2
• Total Enrollment: 70 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-07-10
• Study Completion Date: 2024-07-10

Brief Summary

To evaluate the efficacy and safety of chidamide in combination with camrelizumab and carboplatin or capecitabine in the second and third line treatment of relapsed/metastatic triple-negative breast cancer

Detailed Description

This study is a prospective, single-center, single-arm, open-label clinical study. Successfully screened patients with relapsed/metastatic triple-negative breast cancer will receive chidamide and camrelizumab at the prescribed doses Combined with carboplatin or capecitabine therapy, Chidamide single drug should be taken for lead-in therapy before combined therapy.

Conditions

Triple-negative Breast Cancer

Keywords

chidamide; camrelizumab; carboplatin; capecitabine; relapsed/metastatic; triple-negative breast cancer

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Arm 1

chidamide in combination with camrelizumab and capecitabine

Group Type: EXPERIMENTAL

chidamide

Intervention Type: DRUG

Chidamide, an HDAC inhibitor

camrelizumab

Intervention Type: DRUG

Camrelizumab (AiRuiKa™), a programmed cell death 1 (PD-1) inhibitor being developed by Jiangsu Hengrui Medicine Co. Ltd, recently received conditional approval in China for the treatment of relapsed or refractory classical Hodgkin lymphoma. The drug is also being investigated as a treatment for various other malignancies, including B cell lymphoma, oesophageal squamous cell carcinoma, gastric/gastroesophageal junction cancer, hepatocellular carcinoma, nasopharyngeal cancer and non-squamous, non-small cell lung cancer.

capecitabine

Intervention Type: DRUG

Capecitabine is an oral prodrug of 5-fluorouracil (5-FU) and approved for treatment of various malignancies. Hereditary genetic variants may affect a drug's pharmacokinetics or pharmacodynamics and account for differences in treatment response and adverse events among patients.

Arm 2

chidamide in combination with camrelizumab and carboplatin

Group Type: EXPERIMENTAL

chidamide

Intervention Type: DRUG

Chidamide, an HDAC inhibitor

camrelizumab

Intervention Type: DRUG

Camrelizumab (AiRuiKa™), a programmed cell death 1 (PD-1) inhibitor being developed by Jiangsu Hengrui Medicine Co. Ltd, recently received conditional approval in China for the treatment of relapsed or refractory classical Hodgkin lymphoma. The drug is also being investigated as a treatment for various other malignancies, including B cell lymphoma, oesophageal squamous cell carcinoma, gastric/gastroesophageal junction cancer, hepatocellular carcinoma, nasopharyngeal cancer and non-squamous, non-small cell lung cancer.

carboplatin

Intervention Type: DRUG

Carboplatin \[diammine(1,1-cyclobutanedicarboxylato)platinum(II)\] is one of the most promising second generation platinum compounds. Its greater chemical stability in comparison with cisplatin accounts for its lower reactivity with nucleophilic sites of DNA.

Interventions

chidamide

Chidamide, an HDAC inhibitor

Intervention Type: DRUG

camrelizumab

Camrelizumab (AiRuiKa™), a programmed cell death 1 (PD-1) inhibitor being developed by Jiangsu Hengrui Medicine Co. Ltd, recently received conditional approval in China for the treatment of relapsed or refractory classical Hodgkin lymphoma. The drug is also being investigated as a treatment for various other malignancies, including B cell lymphoma, oesophageal squamous cell carcinoma, gastric/gastroesophageal junction cancer, hepatocellular carcinoma, nasopharyngeal cancer and non-squamous, non-small cell lung cancer.

Intervention Type: DRUG

carboplatin

Carboplatin \[diammine(1,1-cyclobutanedicarboxylato)platinum(II)\] is one of the most promising second generation platinum compounds. Its greater chemical stability in comparison with cisplatin accounts for its lower reactivity with nucleophilic sites of DNA.

Intervention Type: DRUG

capecitabine

Capecitabine is an oral prodrug of 5-fluorouracil (5-FU) and approved for treatment of various malignancies. Hereditary genetic variants may affect a drug's pharmacokinetics or pharmacodynamics and account for differences in treatment response and adverse events among patients.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

1. The patients voluntarily participated in the study and signed the informed consent form

2. 18-75 years old, female

3. EC0G score 0-1

4. Expected survival time ≥ 3 months

5. Patients with recurrent / metastatic breast cancer confirmed by histopathology, with negative expression of ER or PR and negative expression of HER2; Patients with local recurrence need to be confirmed by the investigator that radical resection is impossible

6. Previous anti-tumor regulations (Patients has previously received first-line chemotherapy and disease progression, and at most has received second-line treatment (recurrence and metastasis during adjuvant treatment will be regarded as first-line treatment), Patients who have previously received taxoids drugs)

7. Patients were preferentially enrolled into the chidamide in combination with camrelizumab and capecitabine group( except fo who had failed to receive capecitabine treatment in the past)

8. If the investigator thinks who is suitable to be enrolled in the chidamide in combination with camrelizumab and carboplatin group (such as genetic recombination deficiency, high HRD evaluation score or BRCA1/2 gene mutation, etc.), is preferred to enter this group

9. At least one extracranial measurable lesion according to Response Evaluation Criteria in Solid Tumors (RECIST) criteria version 1.1.

10. The functions of important organs meet the following requirements (no blood components and cell growth factors have been used within 2 weeks before enrollment) ANC ≥ 1.5 × 109 /L; PLT ≥ 75 × 109 /L. Hb ≥ 90 g/L TBIL ≤ 1.5×ULN (upper limit of normal) ALT and AST ≤ 2.5×ULN. Urea / urea nitrogen (BUN) and creatinine (CR) ≤ 1.5 × ULN, or creatinine clearance ≥ 60ml/min/1.73m2 Left ventricular ejection fraction (LVEF) ≥ 50% QTcF(Fridericia correction) < 470 ms INR≤1.5×ULN，APTT≤1.5×ULN

Exclusion Criteria

1. Previously treated with histone deacetylase inhibitors (HDACi)

2. Previously treated with pd-1/pd-l1 inhibitors

3. Untreated imaging confirmed central nervous system metastasis (except asymptomatic brain metastasis)

4. Patients who have received systematic, radical brain or meningeal metastasis treatment (radiotherapy or surgery) in the past, but have been stable for at least 4 weeks as confirmed by imaging, have stopped systemic hormone treatment for more than 2 weeks, and have no clinical symptoms can be included

5. There were ascites, pleural effusion and pericardial effusion with clinical symptoms in the baseline period, requiring drainage, or serous effusion drainage within 4 weeks before the first dose

6. Inability to swallow, intestinal obstruction or other factors affecting drug administration and absorption

7. Systematic treatment such as chemotherapy, molecular targeted therapy or other clinical trial drugs were received within 4 weeks before enrollment, except for observational studies

8. Prior malignancy active within the previous 5 years (except for curable cancers, such as or Non-Melanocytic Tumors of the Skin or carcinoma in situ of the cervix)

9. Had major surgical operation or obvious trauma within 4 weeks before enrollment, or it is expected that the patient will receive major surgical treatment

10. Allergy to the drug components of this study

11. Active HBV and HCV infection; Except for the patients with stable hepatitis B (DNA titer shall not be higher than 500 IU/ml or copy number <1000 copies/ml) and cured hepatitis C (HCV RNA detection is negative)

12. History of immunodeficiency, including HIV test positive, or suffer from other acquired or congenital immunodeficiency diseases, or have a history of organ transplantation

13. Any heart disease, including (1) angina pectoris; (2) Arrhythmia requiring medication or clinically significant; (3) Myocardial infarction; (4) Heart failure; (5) Any other heart disease judged by the researcher as unsuitable for the test; The severity of abnormal cardiac or renal function in screening period is ≥ II

14. Pregnant women, lactating women or fertile women , Or subjects of childbearing age who are unwilling to take effective contraceptive measures during the study period and at least 3 months after the last dose

15. According to the judgment of the investigator, there are concomitant diseases that seriously endanger the safety of the patient or affect the completion of the study (such as severe hypertension, diabetes, thyroid disease, active infection, etc.)

16. History of neurological or mental disorders, including epilepsy or dementia

17. The investigator determined who was not suitable for the study.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Fudan University

OTHER

Sponsor Role: lead

Responsible Party

Xichun Hu

MD

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

Fudan University Shanghai Cancer Center

Shanghai, Shanghai Municipality, China

Countries

China

Central Contacts

Jian Zhang, MD

Role: CONTACT

Phone: +8664175590

Email: syner2000@163.com

Other Identifiers

CSIIT-C21

Identifier Type: -

Identifier Source: org_study_id