Pilot Trial of Eltrombopag in Patients Undergoing Chemotherapy for Malignant Solid Tumors

NCT04485416 | Suspended Phase 1 DMC FDA Drug

• 3 other identifiers: 1602666150124CCPO011
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

Brief Summary

Primary Objective: To assess safety of eltrombopag in pediatric patients undergoing intensive chemotherapy for malignant solid tumors. Secondary Objectives: To assess the efficacy of eltrombopag in increasing platelet count up to 2 weeks after completion of chemotherapy in pediatric patients undergoing intensive chemotherapy for malignant solid tumors. Hypothesis: The hypothesis is that eltrombopag an oral thrombopoietin receptor agonist will increase the platelet count safely and efficaciously in children having chemotherapy induced thrombocytopenia while on therapy for solid tumors.

Conditions

Solid Tumor, Childhood; Solid Tumor

Keywords

chemotherapy; pediatric

Outcome Measures

Primary Outcomes (1)

• Safety objectives

  For safety our end point is liver enzymes ALT, AST up to 5 x upper limit of normal (ULN) in \<80% of patients.

  Through follow up after end of treatment

Secondary Outcomes (1)

• Efficacy objectives

  2 weeks after completion of chemotherapy

Study Arms (1)

Treatment group

EXPERIMENTAL

Subjects will receive eltrombopag

Drug: Eltrombopag

Interventions

Eltrombopag DRUG

Eltrombopag is an orally administered small-molecule nonpeptide TPO-R agonist.

Also known as: Promacta

Treatment group

Eligibility Criteria

• Age: 1 Year - 18 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Patients must meet all of the following criteria to be eligible for study entry.
• Persons aged ≥ 1 to ≤18 years of age.
• Histologically confirmed solid tumors (including rhabdomyosarcoma, Ewings sarcoma, osteosarcoma, non- rhabdomyosarcoma soft tissue sarcoma, peripheral nerve sheath tumor, desmoplastic small round cell tumor, hepatoblastoma, hepatocellular carcinoma, renal cell carcinoma, higher grade neuroblastoma, brain tumors (e.g. medulloblastoma), and other rare solid tumors.
• Currently receiving cancer directed therapy for solid tumor or scheduled to start receiving cancer directed therapy for solid tumor within 60 days.
• Karnofsky Performance Status (KPS) performance status of 80% or greater.
• Life expectancy ≥ 6 months.
• Ability to swallow liquid solution/suspensions or tablets/capsules
• Platelet count \< 150,000µL
• Blood chemistry levels defined by:
• Serum creatinine less than or equal to 2.5 × the upper limit of normal (ULN) range
• Total bilirubin level less than or equal to 1.5 × the upper limit of normal (ULN) range
• AST and ALT \< 3 x upper limit of normal (ULN)
• INR and aPTT less than or equal to 1.5 × ULN (for patients on anticoagulation they must be receiving a stable dose for at least 1 week prior to first treatment)
• Ability to understand and willingness to sign an informed consent form; or Parent/Guardian with ability to understand and willingness to sign an informed consent form.
• Ability to adhere to the study visit schedule and other protocol requirements.

You may not qualify if:

• Patients who meet any of the following criteria will be excluded from study entry.
• Patients with known with hematologic malignancy diagnosis.
• Contraindications to receiving chemotherapy.
• Patients with history of thromboembolic disease or history of thrombophilic risk factors.
• History or current diagnosis of cardiac disease indicating significant risk of safety for patients participating in the study such as uncontrolled or significant cardiac disease, including any of the following:
• Recent myocardial infarction (within last 6 months),
• Uncontrolled congestive heart failure,
• Unstable angina (within last 6 months),
• Clinically significant (symptomatic) cardiac arrhythmias (e.g., sustained ventricular tachycardia, and clinically significant second or third degree AV block without a pacemaker.)
• Long QT syndrome, family history of idiopathic sudden death, congenital long QT syndrome or additional risk factors for cardiac repolarization abnormality, as determined by the investigator.
• Impaired cardiac function, defined as:
• Corrected QTc \>450 msec using Fridericia correction (QTcF) on the screening ECG (using triplicate ECGs),
• Other clinically significant cardio-vascular disease (e.g., uncontrolled hypertension, history of labile hypertension),
• History of known structural abnormalities (e.g. cardiomyopathy).
• Pregnant or lactating women.

Sponsors & Collaborators

• University of California, Davis: lead

Study Sites (1)

University of California Davis Health System, Comprehensive Cancer Center

Sacramento, California, 95817, United States

Location

Related Publications (14)

• Geng W, Kearney S, Nelson S. Upfront eltrombopag monotherapy induces stable hematologic remission in pediatric patients with nonsevere idiopathic aplastic anemia. Pediatr Blood Cancer. 2018 Oct;65(10):e27290. doi: 10.1002/pbc.27290. Epub 2018 Jun 22.

  PMID: 29932285 BACKGROUND

• Townsley DM, Scheinberg P, Winkler T, Desmond R, Dumitriu B, Rios O, Weinstein B, Valdez J, Lotter J, Feng X, Desierto M, Leuva H, Bevans M, Wu C, Larochelle A, Calvo KR, Dunbar CE, Young NS. Eltrombopag Added to Standard Immunosuppression for Aplastic Anemia. N Engl J Med. 2017 Apr 20;376(16):1540-1550. doi: 10.1056/NEJMoa1613878.

  PMID: 28423296 BACKGROUND

• Soff GA, Miao Y, Bendheim G, Batista J, Mones JV, Parameswaran R, Wilkins CR, Devlin SM, Abou-Alfa GK, Cercek A, Kemeny NE, Sarasohn DM, Mantha S. Romiplostim Treatment of Chemotherapy-Induced Thrombocytopenia. J Clin Oncol. 2019 Nov 1;37(31):2892-2898. doi: 10.1200/JCO.18.01931. Epub 2019 Sep 23.

  PMID: 31545663 BACKGROUND

• Li S, Wu R, Wang B, Fu L, Zhu G, Zhou X, Ma J, Zhang L, Qin M. Eltrombopag for Delayed Platelet Recovery and Secondary Thrombocytopenia Following Allogeneic Stem Cell Transplantation in Children. J Pediatr Hematol Oncol. 2019 Jan;41(1):38-41. doi: 10.1097/MPH.0000000000001263.

  PMID: 30080752 BACKGROUND

• Erickson-Miller CL, Kirchner J, Aivado M, May R, Payne P, Chadderton A. Reduced proliferation of non-megakaryocytic acute myelogenous leukemia and other leukemia and lymphoma cell lines in response to eltrombopag. Leuk Res. 2010 Sep;34(9):1224-31. doi: 10.1016/j.leukres.2010.02.005. Epub 2010 Mar 3.

  PMID: 20202683 BACKGROUND

• Sun H, Tsai Y, Nowak I, Liesveld J, Chen Y. Eltrombopag, a thrombopoietin receptor agonist, enhances human umbilical cord blood hematopoietic stem/primitive progenitor cell expansion and promotes multi-lineage hematopoiesis. Stem Cell Res. 2012 Sep;9(2):77-86. doi: 10.1016/j.scr.2012.05.001. Epub 2012 May 14.

  PMID: 22683680 BACKGROUND

• Ballmaier M, Germeshausen M, Krukemeier S, Welte K. Thrombopoietin is essential for the maintenance of normal hematopoiesis in humans: development of aplastic anemia in patients with congenital amegakaryocytic thrombocytopenia. Ann N Y Acad Sci. 2003 May;996:17-25. doi: 10.1111/j.1749-6632.2003.tb03228.x.

  PMID: 12799278 BACKGROUND

• Zeigler FC, de Sauvage F, Widmer HR, Keller GA, Donahue C, Schreiber RD, Malloy B, Hass P, Eaton D, Matthews W. In vitro megakaryocytopoietic and thrombopoietic activity of c-mpl ligand (TPO) on purified murine hematopoietic stem cells. Blood. 1994 Dec 15;84(12):4045-52.

  PMID: 7527664 BACKGROUND

• Qian H, Buza-Vidas N, Hyland CD, Jensen CT, Antonchuk J, Mansson R, Thoren LA, Ekblom M, Alexander WS, Jacobsen SE. Critical role of thrombopoietin in maintaining adult quiescent hematopoietic stem cells. Cell Stem Cell. 2007 Dec 13;1(6):671-84. doi: 10.1016/j.stem.2007.10.008. Epub 2007 Nov 20.

  PMID: 18371408 BACKGROUND

• Erickson-Miller CL, Delorme E, Tian SS, Hopson CB, Landis AJ, Valoret EI, Sellers TS, Rosen J, Miller SG, Luengo JI, Duffy KJ, Jenkins JM. Preclinical activity of eltrombopag (SB-497115), an oral, nonpeptide thrombopoietin receptor agonist. Stem Cells. 2009 Feb;27(2):424-30. doi: 10.1634/stemcells.2008-0366.

  PMID: 19038790 BACKGROUND

• Alexander WS, Roberts AW, Nicola NA, Li R, Metcalf D. Deficiencies in progenitor cells of multiple hematopoietic lineages and defective megakaryocytopoiesis in mice lacking the thrombopoietic receptor c-Mpl. Blood. 1996 Mar 15;87(6):2162-70.

  PMID: 8630375 BACKGROUND

• Kimura S, Roberts AW, Metcalf D, Alexander WS. Hematopoietic stem cell deficiencies in mice lacking c-Mpl, the receptor for thrombopoietin. Proc Natl Acad Sci U S A. 1998 Feb 3;95(3):1195-200. doi: 10.1073/pnas.95.3.1195.

  PMID: 9448308 BACKGROUND

• Kellum A, Jagiello-Gruszfeld A, Bondarenko IN, Patwardhan R, Messam C, Mostafa Kamel Y. A randomized, double-blind, placebo-controlled, dose ranging study to assess the efficacy and safety of eltrombopag in patients receiving carboplatin/paclitaxel for advanced solid tumors. Curr Med Res Opin. 2010 Oct;26(10):2339-46. doi: 10.1185/03007995.2010.510051.

  PMID: 20735290 BACKGROUND

• Olnes MJ, Scheinberg P, Calvo KR, Desmond R, Tang Y, Dumitriu B, Parikh AR, Soto S, Biancotto A, Feng X, Lozier J, Wu CO, Young NS, Dunbar CE. Eltrombopag and improved hematopoiesis in refractory aplastic anemia. N Engl J Med. 2012 Jul 5;367(1):11-9. doi: 10.1056/NEJMoa1200931.

  PMID: 22762314 BACKGROUND

MeSH Terms

Interventions

eltrombopag

Study Officials

• Anjali Pawar, MD

  University of California, Davis

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: SUPPORTIVE CARE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 21, 2020
• First Posted: July 24, 2020
• Study Start: July 16, 2021
• Primary Completion: May 17, 2025
• Study Completion: May 17, 2025
• Last Updated: April 10, 2025

Record last verified: 2025-04

Locations

US (1)