A Clinical Study of Hetrombopag Olamine Tablets for Thrombocytopenia Induced by Chemotherapy in Advanced Breast Cancer

Study Overview
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Brief Summary
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This study now plans to explore the efficacy and safety of hetrombopag in chemotherapy-induced thrombocytopenia in advanced breast cancer, so as to further guide the clinical application of hetrombopag in chemotherapy-induced platelets.

Detailed Description
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Chemotherapy-induced thrombocytopenia increases the risk of hemorrhagic complications, the need for platelet transfusions, and limits the dose of cytotoxic drugs in the treatment of certain malignancies. Thrombopoietin receptor agonist (TPO-RA) has a therapeutic effect on chemotherapy-induced thrombocytopenia (CIT). As an innovative TPO-RA drug, hetrombopag has a more optimized molecular structure and reduced liver and kidney toxicity. A registrational Phase III clinical study in CIT patients is ongoing. This study now plans to explore the efficacy and safety of hetrombopag in chemotherapy-induced thrombocytopenia in advanced breast cancer, so as to further guide the clinical application of hetrombopag in chemotherapy-induced platelets.

Official Title
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A Single-center, Randomized, Self-controlled Exploratory Clinical Study of Hetrombopag Olamine Tablets for Thrombocytopenia Induced by Chemotherapy in Advanced Breast Cancer

Conditions
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Breast Cancer

Intervention / Treatment
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* Drug: Hetrombopag
* Drug: rh-TPO


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: The patients signed the informed consent and voluntarily joined the study; Age 18-75 years old, male or female; Patients with advanced breast cancer diagnosed by histopathology or cytology, who are receiving and continue to receive the same chemotherapy regimen; Can accept the current chemotherapy regimen (must be platinum-containing chemotherapy regimen: lobaplatin, carboplatin, cisplatin, etc.) for at least 2 cycles; The first occurrence of platelets <50×109/L in the current chemotherapy cycle; The investigator determines that the patient can receive hetrombopag administration; Neutrophil count ≥ 1.0×109/L, hemoglobin ≥ 80g/L before administration of Haitrombopag; Life expectancy at screening ≥ 12 weeks; ECOG: 0-1; The main organ functions are normal, and there are no serious complications. Exclusion Criteria: Women who are pregnant or breastfeeding; Unable to understand the research nature of the research or have not obtained informed consent; The investigator judges other circumstances that are not suitable for inclusion in the study; Thrombocytopenia caused by other causes (chronic liver disease, sepsis, disseminated intravascular coagulation, immune thrombocytopenia, etc.); Patients with unstable angina pectoris, congestive heart failure, uncontrolled hypertension, uncontrolled arrhythmia or recent history (within 1 year of screening) of myocardial infarction; Those with a history of blood disease or tumor bone marrow infiltration; Those who received simultaneous radiotherapy and those who received pelvic radiotherapy in the past; Arterial or venous thrombotic events within the past 6 months; There are currently uncontrollable infections; Clinical manifestations of severe bleeding within 2 weeks before screening, such as gastrointestinal or central nervous system bleeding; Need emergency treatment, such as superior vena cava syndrome, spinal cord compression; The absolute value of neutrophils is less than 1.0×109/L, and the hemoglobin is less than 80g/L, and granulocyte colony-stimulating factor, red blood cells, and EPO infusion therapy in accordance with clinical routine are allowed; Obvious abnormal liver function: patients without liver metastases, ALT/AST>3ULN (upper limit of normal value), TBIL>3ULN; patients with liver metastases, ALT/AST≥5ULN, TBIL≥5ULN; Abnormal renal function: serum creatinine ≥ 1.5ULN or eGFR ≤ 60 ml/min (Cockcroft-Gault formula); 16. Received thrombopoietin receptor agonist drugs (such as Eltrombopag, Romigrastim), or recombinant human thrombopoietin (rhTPO), recombinant human interleukin-11 (rhIL) within 1 month before screening -11) Treatment; 17. Received platelet transfusion within 3 days before randomization; 18. Patients with known or expected hypersensitivity or intolerance to the active ingredients or excipients of Hetrombopag ethanolamine tablets.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: hetrombopag Olamine tablets<br>The first chemotherapy cycle (single center, open label, randomized controlled): When platelets were <50*109/L, oral hetrombopag 7.5 mg/day was started. When the platelet count is >100*109/L, the administration is suspended. 2nd chemotherapy cycle (exploratory study): Prophylactic use (60 cases in the test group and the control group): oral hetrombopag 7.5 mg/day (initial dose) was started on d2 after chemotherapy for 14 days. | Drug: Hetrombopag<br>* The first chemotherapy cycle (single center, open label, randomized controlled): When platelets were <50*109/L, oral hetrombopag 7.5 mg/day was started. When the platelet count is >100*109/L, the administration is suspended. 2nd chemotherapy cycle (exploratory study): Prophylactic use (60 cases in the test group and the control group): oral hetrombopag 7.5 mg/day (initial dose) was started on d2 after chemotherapy for 14 days.<br>|
| Other: rhTPO<br>The first chemotherapy cycle (single center, open label, randomized controlled): Start using rh-TPO 15000 units/day (subcutaneous injection) when platelets are less than 50*109/L. When the platelet count is more than 100*109/L, the administration is suspended. 2nd chemotherapy cycle (exploratory study): Prophylactic use (60 cases in the test group and the control group): oral hetrombopag 7.5 mg/day (initial dose) was started on d2 after chemotherapy for 14 days. | Drug: Hetrombopag<br>* The first chemotherapy cycle (single center, open label, randomized controlled): When platelets were <50*109/L, oral hetrombopag 7.5 mg/day was started. When the platelet count is >100*109/L, the administration is suspended. 2nd chemotherapy cycle (exploratory study): Prophylactic use (60 cases in the test group and the control group): oral hetrombopag 7.5 mg/day (initial dose) was started on d2 after chemotherapy for 14 days.<br>Drug: rh-TPO<br>* The first chemotherapy cycle (single center, open label, randomized controlled): Start using rh-TPO 15000 units/day (subcutaneous injection) when platelets are less than 50*109/L. When the platelet count is more than 100*109/L, the administration is suspended. 2nd chemotherapy cycle (exploratory study): Prophylactic use (60 cases in the test group and the control group): oral hetrombopag 7.5 mg/day (initial dose) was started on d2 after chemotherapy for 14 days.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Comparison of response rates to platelet-raising therapy in two chemotherapy cycles | Definition of response: 1. No chemotherapy regimen adjustment due to thrombocytopenia (such as chemotherapy delay ≥ 5 days, and/or chemotherapy dose reduction ≥ 20%, chemotherapy discontinuation, etc.; 2. No platelet-raising rescue therapy; 3. No Grade 4 myelosuppression; 4. Grade 3 myelosuppression for a duration of ≤ 1 week) | 30day±3day after the last administration of Hetrombopag Olamine Tablets | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The lowest platelet value after chemotherapy; | The lowest platelet value after chemotherapy; | 30day±3day after the last administration of Hetrombopag Olamine Tablets | 
| The incidence of platelets <50×109/L and <25×109/L; | The incidence of platelets <50×109/L and <25×109/L; | 30day±3day after the last administration of Hetrombopag Olamine Tablets | 
| The duration of platelets <50×109/L and <25×109/L; | The duration of platelets <50×109/L and <25×109/L; | 30day±3day after the last administration of Hetrombopag Olamine Tablets | 
| The time for platelets to recover to more than 100×109/L; | The time for platelets to recover to more than 100×109/L; | 30day±3day after the last administration of Hetrombopag Olamine Tablets | 
| latelet recovery to the highest value after chemotherapy; | latelet recovery to the highest value after chemotherapy; | 30day±3day after the last administration of Hetrombopag Olamine Tablets | 
| the incidence of adverse events; | the incidence of adverse events; | 30day±3day after the last administration of Hetrombopag Olamine Tablets |