Efficacy and Safety of Avatrombopag in Cancer Patients With Thrombocytopenia

Efficacy and Safety of Avatrombopag in Cancer Patients With Thrombocytopenia Induced by Targeted Therapy and Immunotherapy Combination Treatment

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

Study Overview

• Status: Recruiting
• Conditions: Thrombocytopenia; Avatrombopag
• Intervention / Treatment: Drug: Avatrombopag

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.

• Study Type: Interventional
• Enrollment (Anticipated): 30
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Yanyu Wang, MD; Phone Number: +86 15810784518; Email: pumcwyy950105@163.com

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100730
      • Recruiting
      • Peking Union Medical College Hospital
      • Contact: Yanyu Wang, MD; Phone Number: +86-15810784518; Email: pumcwyy950105@163.com
      • Contact: Xiao-Bo Xiao-Bo, MD; Phone Number: +86-138-1167-5126; Email: yangxiaobo67@pumch.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 85 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

EXPERIMENTAL: 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.

Drug: 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of participants' PLT	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.	one year

Secondary Outcome Measures

Outcome Measure	Time Frame
Number of days required for PLT to reach ≥50×109/L after treatment;	one year
Number of days required for PLT to reach ≥75×109/L after treatment;	one year
Percentage of subjects without platelet transfusion within 20 days of treatment;	one year
Percentage of subjects without clinically relevant bleeding within 20 days of treatment.	one year

Collaborators and Investigators

• Sponsor: Peking Union Medical College Hospital

Publications and helpful links

General Publications

• Arora S, Balasubramaniam S, Zhang W, Zhang L, Sridhara R, Spillman D, Mathai JP, Scott B, Golding SJ, Coory M, Pazdur R, Beaver JA. FDA Approval Summary: Pembrolizumab plus Lenvatinib for Endometrial Carcinoma, a Collaborative International Review under Project Orbis. Clin Cancer Res. 2020 Oct 1;26(19):5062-5067. doi: 10.1158/1078-0432.CCR-19-3979. Epub 2020 Apr 15.
• Lingen MW, Kalmar JR, Karrison T, Speight PM. Critical evaluation of diagnostic aids for the detection of oral cancer. Oral Oncol. 2008 Jan;44(1):10-22. doi: 10.1016/j.oraloncology.2007.06.011. Epub 2007 Sep 6.
• Adelstein DJ, Li Y, Adams GL, Wagner H Jr, Kish JA, Ensley JF, Schuller DE, Forastiere AA. An intergroup phase III comparison of standard radiation therapy and two schedules of concurrent chemoradiotherapy in patients with unresectable squamous cell head and neck cancer. J Clin Oncol. 2003 Jan 1;21(1):92-8. doi: 10.1200/JCO.2003.01.008.
• Pignon JP, le Maitre A, Maillard E, Bourhis J; MACH-NC Collaborative Group. Meta-analysis of chemotherapy in head and neck cancer (MACH-NC): an update on 93 randomised trials and 17,346 patients. Radiother Oncol. 2009 Jul;92(1):4-14. doi: 10.1016/j.radonc.2009.04.014. Epub 2009 May 14.
• Suntharalingam M, Haas ML, Conley BA, Egorin MJ, Levy S, Sivasailam S, Herman JM, Jacobs MC, Gray WC, Ord RA, Aisner JA, Van Echo DA. The use of carboplatin and paclitaxel with daily radiotherapy in patients with locally advanced squamous cell carcinomas of the head and neck. Int J Radiat Oncol Biol Phys. 2000 Apr 1;47(1):49-56. doi: 10.1016/s0360-3016(00)00408-9.
• Garden AS, Harris J, Vokes EE, Forastiere AA, Ridge JA, Jones C, Horwitz EM, Glisson BS, Nabell L, Cooper JS, Demas W, Gore E. Preliminary results of Radiation Therapy Oncology Group 97-03: a randomized phase ii trial of concurrent radiation and chemotherapy for advanced squamous cell carcinomas of the head and neck. J Clin Oncol. 2004 Jul 15;22(14):2856-64. doi: 10.1200/JCO.2004.12.012.
• Adkins D, Ley J, Michel L, Wildes TM, Thorstad W, Gay HA, Daly M, Rich J, Paniello R, Uppaluri R, Jackson R, Trinkaus K, Nussenbaum B. nab-Paclitaxel, cisplatin, and 5-fluorouracil followed by concurrent cisplatin and radiation for head and neck squamous cell carcinoma. Oral Oncol. 2016 Oct;61:1-7. doi: 10.1016/j.oraloncology.2016.07.015. Epub 2016 Jul 29.
• Reddy BK, Lokesh V, Vidyasagar MS, Shenoy K, Babu KG, Shenoy A, Naveen T, Joseph B, Bonanthaya R, Nanjundappa, Bapsy PP, Loknatha, Shetty J, Prasad K, Tanvir Pasha CR. Nimotuzumab provides survival benefit to patients with inoperable advanced squamous cell carcinoma of the head and neck: a randomized, open-label, phase IIb, 5-year study in Indian patients. Oral Oncol. 2014 May;50(5):498-505. doi: 10.1016/j.oraloncology.2013.11.008. Epub 2014 Mar 6.

Study record dates

Study Major Dates

• Study Start (ANTICIPATED): June 6, 2021
• Primary Completion (ANTICIPATED): December 31, 2021
• Study Completion (ANTICIPATED): December 31, 2021

Study Registration Dates

• First Submitted: April 28, 2021
• First Submitted That Met QC Criteria: May 19, 2021
• First Posted (ACTUAL): May 21, 2021

Study Record Updates

• Last Update Posted (ACTUAL): May 21, 2021
• Last Update Submitted That Met QC Criteria: May 19, 2021
• Last Verified: April 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Hematologic Diseases; Blood Platelet Disorders; Thrombocytopenia
• Other Study ID Numbers: SKX-CIT-002

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No