Efficacy and Safety of Avatrombopag in Cancer Patients With Thrombocytopenia

NCT ID: NCT04896528

Last Updated: 2021-05-21

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE2
• Total Enrollment: 30 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-06-06
• Study Completion Date: 2021-12-31

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.

Conditions

Thrombocytopenia; Avatrombopag

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Avatrombopag

Avartripopa is a new generation of oral TPO receptor agonist that simulates the biological effects of TPO in vitro and in vivo.

TPO stimulates megakaryocytes through binding and activation of TPO receptor, which is expressed in hematopoietic stem cells, megakaryotic cell lines and platelets.

By binding to the transmembrane region of the thrombopoietin receptor, Ava Tripopa activates the thrombopoietin receptor in humans, stimulates signal transduction and mimics the biological effects of thrombopoietin, leading to an increase in platelet count.

Group Type: EXPERIMENTAL

Avatrombopag

Intervention Type: DRUG

• Participants meeting the eligibility criteria receive Avatrombopag treatment (orally, 60 mg/day), for a maximum course of 20 days.
• Investigation product withdrawal: PLT ≥75×109/L or increases by at least 50×109/L from the lowest value after targeted therapy and immunotherapy combination treatment.

Interventions

Avatrombopag

• Participants meeting the eligibility criteria receive Avatrombopag treatment (orally, 60 mg/day), for a maximum course of 20 days.
• Investigation product withdrawal: PLT ≥75×109/L or increases by at least 50×109/L from the lowest value after targeted therapy and immunotherapy combination treatment.

Intervention Type: DRUG

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)

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 85 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Peking Union Medical College Hospital

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Haitao Haitao, Prof

Role: STUDY_CHAIR

Peking Union Medical College Hospital (PUMCH)

Locations

Peking Union Medical College Hospital

Beijing, Beijing Municipality, China

Site Status: RECRUITING

Countries

China

Central Contacts

Yanyu Wang, MD

Role: CONTACT

pumcwyy950105@163.com

+86 15810784518

Haitao Haitao, Prof

Role: CONTACT

Facility Contacts

Yanyu Wang, MD

Role: primary

pumcwyy950105@163.com

+86-15810784518

Xiao-Bo Xiao-Bo, MD

Role: backup

yangxiaobo67@pumch.cn

+86-138-1167-5126

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Other Identifiers

SKX-CIT-002

Identifier Type: -

Identifier Source: org_study_id