Clinical trial NCT04896528: Efficacy and Safety of Avatrombopag in Cancer Patients With Thrombocytopenia
Official title: Efficacy and Safety of Avatrombopag in Cancer Patients With Thrombocytopenia Induced by Targeted Therapy and Immunotherapy Combination Treatment
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Thrombocytopenia
Avatrombopag
Lead sponsor: Peking Union Medical College Hospital
Sponsor class: OTHER
First posted: 2021-05-21
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Patients receiving combined targeted therapy (including but not limited to tyrosine kinase inhibitors, cyclin-dependent kinase inhibitors) with immunotherapy (including but not limited to PD-1 inhibitors and/or PD-L1 inhibitors and/or CTLA-4 inhibitors); Patients experienced grade III or above thrombocytopenia (PC ≤50×109/L) at least once within 48 h of the screening period;
Primary purpose: TREATMENT

Brief summary: To evaluate the efficacy and safety of Avatrombopag in patients with thrombocytopenia induced by targeted therapy and immunotherapy combination treatment, and provide evidence-based medication for the clinical use of Avatrombopag in patients with PC ≤50×109/L

Detailed description: This phase II trial is a single-arm, non-randomized and single-center clinical study.

It is estimated that 30 patients who met the study criteria will be enrolled in PUMCH and treated with Avatrombopag. The investigators will follow up and collect subjects' data each month to evaluate the efficacy and safety of treatment. Primary outcome measure is percentage of participants whose PLT reaches ≥75×109/L, or increases by ≥50×109/L or ≥100% from baseline at least once within 20 days of initial treatment.

Secondary outcome measure:1)Number of days required for PLT to reach ≥50×109/L after treatment; 2)Number of days required for PLT to reach ≥75×109/L after treatment; 3)Percentage of subjects without platelet transfusion within 20 days of treatment; 4)Percentage of subjects without clinically relevant bleeding within 20 days of treatment.

Study Type: Interventional. Masking: Open Label.

Eligibility criteria: Inclusion Criteria:

Each participant must meet all of the following criteria:

1. Male or female, 18\~85 years of age;
2. Diagnosis of malignant solid tumor;
3. Participants receiving combined targeted therapy (including but not limited to tyrosine kinase inhibitors, cyclin-dependent kinase inhibitors) with immunotherapy (including but not limited to PD-1 inhibitors and/or PD-L1 inhibitors and/or CTLA-4 inhibitors);
4. Participants experienced grade III or above thrombocytopenia (PC ≤50×109/L) at least once within 48 h of the screening period; No oral platelet-enhancing drugs were given before enrollmen.
5. ECGO performance status ≤2;
6. Blood test:

   * Hemoglobin (Hb) ≥ 9.0 g/dL;
   * Absolute neutrophils count (ANC) ≥ 1,500/μL;
7. Liver and renal functions:

   * Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 3\*ULN (Upper Limits of Normal);
   * Serum bilirubin ≤ 1.5\*ULN;
   * Albumin ≥ 2.5 g/dL;
   * Serum creatinine ≤ 1.5\*ULN (CTCAE Grade Ⅰ)
8. Participants able to oral medication;
9. Expected survival time ≥12 weeks during screening period;
10. Participants with negative urine or serum pregnancy test during screening period; fertile potential participants must agree to use contraception for the whole study period and 30 days after discontinuity of investigational product treatment (infertile potential was defined as the condition including hysterectomy and bilateral oophorectomy, bilateral salpingectomy, tubal ligation and postmenopausal);
11. Participants in the trial is voluntary and must strictly abide by the protocol;
12. Participants must sign the written informed consent form.

Exclusion Criteria:

Participants meeting any of the following criteria will be excluded from the study:

1. Participants has any history of active congestive heart failure \[New York Heart Association (NYHA) Grade III-IV\], symptomatic ischemia, uncontrolled arrhythmia, pericardial disease, or myocardial infarction during the first 4 months of enrollment;
2. Participants finished major operation within less than 28 days and for minor operation within less than 3 days;
3. Participants had clinically significant acute or active bleeding (e.g., gastrointestinal or central nervous system) within 7 days prior to screening;
4. Participants has medical-known hereditary prethrombotic syndrome (such as factor V Leiden mutation, prothrombin G20210A mutation or hereditary antithrombin III deficiency);
5. Participants has a history of arterial or venous thrombosis within 3 months prior to screening;
6. Participants had treatment with heparin and warfarin within 7 days prior to screening;
7. Participants has history of chronic thrombocytopenia or hemorrhagic disease, or thrombocytopenia induced by other reasons besides targeted therapy and immunotherapy combination treatment(e.g., chronic liver disease or immune thrombocytopenic purpura);
8. Participants had the treatment of platelet transfusion within 3 days before enrollment;
9. Participants had administration of platelet growth factor (e.g., rhTPO, rhIL-11, Eltrombopag, or Romiplostim) for the treatment of thrombocytopenia induced by targeted therapy and immunotherapy combination treatment within 2 weeks prior to screening;
10. Participants' thrombocytopenia responded effectively to hormone therapy;
11. Participants are allergic to Avatrombopag or any of its excipients;
12. Participants were in any other clinical trial of investigational product or device within 30 days prior to screening, except for observational study;
13. Participants have any known concomitant history that may impair the safe completion of the study as assessed by the investigator, such as unstable angina, renal failure due to hemodialysis, or active infection requiring intravenous antibiotics;
14. Participants are pregnant or lactating at the time of screening (as demonstrated by a positive serum β-HCG test) or baseline visit (positive urine β-HCG test)

Primary outcomes:
measure: Percentage of participants' PLT
timeFrame: one year
Secondary outcomes:
measure: Number of days required for PLT to reach ≥50×109/L after treatment;
timeFrame: one year
measure: Number of days required for PLT to reach ≥75×109/L after treatment;
timeFrame: one year
measure: Percentage of subjects without platelet transfusion within 20 days of treatment;
timeFrame: one year
measure: Percentage of subjects without clinically relevant bleeding within 20 days of treatment.
timeFrame: one year
Other outcomes:
Locations:
city: Beijing
country: China
facility: Peking Union Medical College Hospital
state: Beijing
Study officials:
affiliation: Peking Union Medical College Hospital (PUMCH)
name: Haitao Haitao, Prof
role: STUDY_CHAIR
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