The Efficacy and Safety of Hetrombopag as Secondary Prevention to Chemotherapy-induced Thrombocytopenia in Patients With Gynecologic Malignancies

Study Overview
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Brief Summary
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Chemotherapy is an important treatment strategy for gynecological malignancies, such as ovarian cancer, advanced endometrial cancer, cervical cancer. Chemotherapy-induced thrombocytopenia (CIT) is one of the most common chemotherapy-related hematologic toxicities and can increase the risk of bleeding, prolong hospital stays, increase healthcare costs, and, in severe cases, death. It can lead to a reduction in the intensity of chemotherapy doses, delay the next cycle of chemotherapy, or even termination of treatment, thereby affecting the antitumor effect and adversely affecting the long-term survival of these patients. Literature and our data show that when patients develop grade II or worse CIT, the incidence of grade II and above CIT after the next cycle of chemotherapy is 85-92%. Hetrombopag is one of the thrombopoietin receptor agonist (TPO-RA) that has been studied to explore its role in the treatment and prevention of CIT in multiple solid tumors. In order to find out the secondary prevention efficacy of CIT, it is planned to carry out this single-arm prospective study by recruiting 48 patients with gynecological malignancies with grade II CIT or above after chemotherapy, whose platelets has returned to normal after the routine clinical intervention, and then plan to have the next cycle of chemotherapy. The intervention strategy is taking hetrombopag 5mg/day within 24 hours after chemotherapy, then observe the incidence rate of grade II CIT. The endpoint of this study is to assess the effectiveness and safety of hetrombopag for preventing CIT in patients with gynaecological malignancies.

Official Title
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The Efficacy and Safety of Hetrombopag as Secondary Prevention to Chemotherapy-induced Thrombocytopenia in Patients With Gynecologic Malignancies（the SPRIT TRIAL）

Conditions
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Chemotherapy-induced Thrombocytopenia

Intervention / Treatment
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* Drug: Hetrombopag


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 18-75 years. Pathological diagnosis of gynecological malignancies such as ovarian cancer, cervical cancer, endometrial cancer, etc. Grade 2 or above thrombocytopenia occurred after the previous cycle of chemotherapy, and the platelet count recovered to ≥100×109/L through routine clinical intervention. Patients plan to receive at least one cycle of chemotherapy containing platinum and paclitaxel. Eastern Cooperative Oncology Group Physical Score(ECOG PS) : 0-2. Estimated survival≥ 12 weeks. Exclusion Criteria: Have received pelvic, spinal radiotherapy and bone field irradiation within 3 months before screening. Grade I and above thrombocytopenia caused by other diseases within 6 months before screening, including but not limited to chronic liver disease, hypersplenism, infection and bleeding,or hematopoietic system diseases . Clinical manifestations of severe bleeding within 2 weeks before screening, including but not limited to gastrointestinal or central nervous system bleeding. Abnormal liver function: patients without liver metastases, Alanine aminotransferase（ALT）/aspartate aminotransferase（AST）>3 upper limit of normal value (ULN); Patients with liver metastases, Alanine aminotransferase（ALT）/aspartate aminotransferase（AST) ≥5 upper limit of normal value (ULN). Abnormal renal function: serum creatinine ≥ 1.5upper limit of normal value (ULN).

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: Prevention
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Hetrombopag<br>All the 48 patients will be given hetrombopag 5mg/day within 24 hours after chemotherapy | Drug: Hetrombopag<br>* All the recruited 48 patients will take hetrombopag 5mg/day within 24 hours after chemotherapy<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| efficacy of hetrombopag | incidence of thrombocytopenia according to Common Terminology Criteria for Adverse Events 5.0(CTCAE5.0) | from the date of recruitment to the time of 14 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| reduction of dose | the percentage of dose reduction due to thrombocytopenia | from the date of recruitment to the time of 3 weeks | 
| adverse reactions | Incidence of adverse reactions | from the date of recruitment to the time of 3 weeks |