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

Phase 2

Recruiting

• Conditions: Breast Cancer
• Interventions: Drug: Hetrombopag; Drug: rh-TPO

• Registration Number: NCT05394285
• Lead Sponsor: Henan Cancer Hospital

Brief Summary

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

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.

Study Timeline

• Study First Submitted: 2022-04-30
• Study First Submitted QC: 2022-05-26
• Study First Posted: 2022-05-27
• Study Start: 2022-08-19
• Status Verified: 2023-09
• Last Update Submitted: 2024-02-29
• Last Update Posted: 2024-03-04
• Primary Completion: 2024-12-28
• Study Completion: 2024-12-28

Recruitment & Eligibility

• Status: RECRUITING
• Sex: Female
• Target Recruitment: 60

Inclusion Criteria

1. The patients signed the informed consent and voluntarily joined the study;
2. Age 18-75 years old, male or female;
3. Patients with advanced breast cancer diagnosed by histopathology or cytology, who are receiving and continue to receive the same chemotherapy regimen;
4. Can accept the current chemotherapy regimen (must be platinum-containing chemotherapy regimen: lobaplatin, carboplatin, cisplatin, etc.) for at least 2 cycles;
5. The first occurrence of platelets <50×109/L in the current chemotherapy cycle;
6. The investigator determines that the patient can receive hetrombopag administration;
7. Neutrophil count ≥ 1.0×109/L, hemoglobin ≥ 80g/L before administration of Haitrombopag;
8. Life expectancy at screening ≥ 12 weeks;
9. ECOG: 0-1;
10. The main organ functions are normal, and there are no serious complications.

Exclusion Criteria

1. Women who are pregnant or breastfeeding;

2. Unable to understand the research nature of the research or have not obtained informed consent;

3. The investigator judges other circumstances that are not suitable for inclusion in the study;

4. Thrombocytopenia caused by other causes (chronic liver disease, sepsis, disseminated intravascular coagulation, immune thrombocytopenia, etc.);

5. Patients with unstable angina pectoris, congestive heart failure, uncontrolled hypertension, uncontrolled arrhythmia or recent history (within 1 year of screening) of myocardial infarction;

6. Those with a history of blood disease or tumor bone marrow infiltration;

7. Those who received simultaneous radiotherapy and those who received pelvic radiotherapy in the past;

8. Arterial or venous thrombotic events within the past 6 months;

9. There are currently uncontrollable infections;

10. Clinical manifestations of severe bleeding within 2 weeks before screening, such as gastrointestinal or central nervous system bleeding;

11. Need emergency treatment, such as superior vena cava syndrome, spinal cord compression;

12. 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;

13. 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;

14. Abnormal renal function: serum creatinine ≥ 1.5ULN or eGFR ≤ 60 ml/min (Cockcroft-Gault formula);

15. 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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
rhTPO	rh-TPO	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.
rhTPO	Hetrombopag	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.
hetrombopag Olamine tablets	Hetrombopag	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.

Primary Outcome Measures

Name	Time	Method
Comparison of response rates to platelet-raising therapy in two chemotherapy cycles	30day±3day after the last administration of Hetrombopag Olamine Tablets	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)

Secondary Outcome Measures

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

Trial Locations

Locations (1)

Henan Cancer Hospital; 🇨🇳 Zhengzhou, China