Chemotherapy Induced Thrombocytopenia
Conditions
Brief summary
The study consists of five sequential periods: * Screening (≤ 4 weeks) * Correction phase * Maintenance phase (first treatment cycle, Cycle 1) * Observation phase (second treatment cycle, Cycle 2) * Follow-up Eligible subjects are gynaecological-cancer patients who developed ≥ grade-2 cancer-therapy-induced thrombocytopenia (CTIT) after anti-tumour therapy, i.e. platelet count \< 75 × 10⁹/L. * Stage 1\*\* - Prospective, multicentre, randomised clinical study (to inform the confirmatory stage 2) \*\*Cohort 1 (n = 30)\*\* Correction: hetrombopag 7.5 mg p.o. daily until PLT ≥ 100 × 10⁹/L. Within 24 h after completion of Cycle 1 anti-cancer therapy (end of chemotherapy if combined; otherwise end of investigational product on that day) restart hetrombopag 7.5 mg p.o. daily and continue until the last day of Cycle 1 (C1D21). \*\*Cohort 2 (n = 30)\*\* Correction: hetrombopag 7.5 mg p.o. daily until PLT ≥ 100 × 10⁹/L. During Cycle 1, monitor PLT closely; if PLT falls \< 75 × 10⁹/L, initiate hetrombopag 7.5 mg p.o. daily and continue until C1D21. \*\*Stage 2\*\* - Prospective, multicentre, randomised, controlled clinical study \*(preliminary design; sample size and details will be refined after stage-1 results)\* \*\*Experimental arm (n = 92)\*\* Correction: hetrombopag 7.5 mg p.o. daily until PLT ≥ 100 × 10⁹/L. Restart within 24 h after completion of Cycle 1 therapy and continue daily until C1D21. \*\*Control arm (n = 92)\*\* Correction: hetrombopag 7.5 mg p.o. daily until PLT ≥ 100 × 10⁹/L. During Cycle 1, monitor PLT; if PLT \< 75 × 10⁹/L, initiate hetrombopag 7.5 mg p.o. daily until C1D21. \*\*Correction-phase rules\*\* Discontinue hetrombopag once PLT ≥ 100 × 10⁹/L. If after ≥ 14 days of hetrombopag correction PLT remains \< 100 × 10⁹/L and the next treatment cycle has not started, the investigator may resume hetrombopag or institute alternative platelet-enhancing rescue therapy at their discretion.
Interventions
DRUGhetrombopag 7.5 mg orally once daily
Correction phase: start hetrombopag 7.5 mg orally once daily and continue until platelet count normalizes (PLT ≥ 100 × 10⁹/L). Within 24 h after completion of Cycle 1 anti-cancer therapy-defined as the end of chemotherapy infusion if on a combined regimen, or the end of study drug administration on that day for non-chemotherapy regimens-restart hetrombopag 7.5 mg orally once daily and maintain until the last day of Cycle 1 (C1D21).
Sponsors
Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
Key eligibility criteria: 1. Female, aged 18-75 years (inclusive). 2. Histopathologically or cytologically confirmed ovarian, cervical, endometrial, or other gynecologic malignancy. 3. Thrombocytopenia (platelet count \< 75 × 10⁹/L) attributable to anti-cancer therapy, with ≥ 2 further treatment cycles planned. 4. ECOG performance status 0-1. 5. Estimated life expectancy ≥ 12 weeks. 6. Women of child-bearing potential must have a negative serum pregnancy test within 7 days before first dose, not be breastfeeding, and agree to use effective contraception from study entry through 7 days after the last dose. 7. Able to provide written informed consent and comply with study procedures.
Exclusion criteria
1. Pregnant or lactating women. 2. Unable to understand the study nature or give informed consent. 3. History of any arterial or venous thrombosis (stroke, TIA, MI, DVT, PE) or clinical/laboratory evidence of thrombophilia. 4. Cardiac disease within 3 months before screening: NYHA class III/IV heart failure, symptomatic arrhythmia requiring therapy, MI, arrhythmias increasing thrombotic risk (e.g., atrial fibrillation), or QTc prolongation. 5. Thrombocytopenia not related to anti-cancer therapy, active severe bleeding, or refractory persistent thrombocytopenia. 6. Significant hepatic impairment: * No liver metastases: ALT/AST \> 3 × ULN or TBL \> 3 × ULN * Liver metastases: ALT/AST ≥ 5 × ULN or TBL ≥ 5 × ULN 7. Known or suspected hypersensitivity/intolerance to TPO-receptor agonists or hetrombopag excipients. 8. Concomitant use of agents that may affect platelet count (e.g., Chinese herbal medicines, other thrombopoietic agents, antiplatelet drugs). 9. Receipt within 1 month before screening of TPO-RAs (eltrombopag, romiplostim, etc.), rhTPO, or rhIL-11. 10. Platelet transfusion within 3 days before randomisation/first dose. 11. Any condition that, in the investigator's opinion, renders the patient unsuitable for the study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of subjects achieving a treatment response | At the end of the first cycle (each cycle is 28 days). | Treatment-response criteria (all must be met): 1. Completed the entire first treatment cycle (Cycle 1) with a platelet count ≥ 100 × 10⁹/L at C1D21 (window: +4 days). 2. Received no rescue therapy for thrombocytopenia (e.g., platelet transfusion, rhIL-11, rhTPO) from the start of Cycle 1 through C1D21 (window: +4 days). 3. Had no Cycle 2 modifications attributable to CTIT: no delay ≥ 4 days, no dose reduction ≥ 15 %, and no treatment suspension. |
Contacts
CONTACTHuaiwu Lu
PRINCIPAL_INVESTIGATORHuaiwu Lu
Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University
Outcome results
None listed