Eltrombopag is an orally administered, small molecule thrombopoietin receptor (TPO-R) agonist that stimulates platelet production by a mechanism similar, but not identical to endogenous TPO. Eltrombopag interacts with the transmembrane domain of the TPO-R (also known as C-MPL) leading to increased platelet production (Erickson-Miller, 2010; Sun et al, 2012).~Eltrombopag is indicated for the treatment of thrombocytopenia in adult and pediatric patients one year and older with chronic immune (idiopathic) thrombocytopenia (ITP) who have had an insufficient response to corticosteroids, immunoglobulins, or splenectomy.~Eltrombopag has also been approved for the treatment of thrombocytopenia in adult patients with chronic hepatitis C to allow for the initiation and maintenance of interferon-based therapy and for the treatment of cytopenias in adult patients with severe aplastic anemia (SAA) who have had insufficient responses to immunosuppressive therapy.~This is an open label, single center pilot trial of eltrombopag in pediatric patients receiving cancer directed therapy for solid tumors. The purpose of this study is to explore the platelet supportive care effects and safety of eltrombopag in pediatric patients (ages one to 18 years of age) undergoing intensive chemotherapy for malignant solid tumors. The primary endpoint will be to determine the safety of eltrombopag in pediatric patients undergoing intensive chemotherapy for malignant solid tumors using CTCAE v5.0 criteria. The secondary endpoint will be to determine the efficacy of eltrombopag in pediatric patients undergoing intensive chemotherapy for malignant solid tumors. These objectives will be assessed by evaluating drug-related toxicities, the platelet response in patients and the proportion of subjects receiving eltrombopag who are platelet transfusion-free during the time period of chemotherapy.~The study will enroll 10 subjects with histologically confirmed solid tumors, including but not limited to rhabdomyosarcoma, Ewing 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, medulloblastoma, or other rare malignant solid tumors.~The cancer directed therapy will be part of standard treatment for each patient and will consist of two to four cycles of chemotherapy (or as many as clinically indicated per physician discretion) to reduce tumor burden, followed by surgery in the majority of cases, and/or radiation in a minority of cases, or both in rare cases at various times in the course of treatment. After recovery from the surgery and/or radiation, chemotherapy and eltrombopag will be resumed until completion. Each cycle of chemotherapy will be approximately two to four weeks (14 to 28 days) in length with chemotherapy administered for one to five days per cycle. The duration of chemotherapy varies by regimen and underlying malignancy.~Patients will initiate eltrombopag on the first day following the completion of chemotherapy for each cycle (e.g., chemo is administered on Days 1-5, eltrombopag to start on Day 6). Eltrombopag will be administered daily and the dose will be age dependent (see Table 5). Children less than 6 years of age will receive a starting dose of 25 mg by mouth once daily, taken on empty stomach one hour before or two hours after a meal. For children greater than or equal to 6 years of age, the starting dose will be 75 mg by mouth once daily. Doses shall be reduced in patients of Asian ancestry (e.g., Japanese, Chinese, Taiwanese, or Korean): for those patients greater than or equal to 6 years of age, the starting dose will be 50 mg by mouth once daily and for those patients less than 6 years old, the starting dose will be 12.5 mg by mouth once daily. Eltrombopag will be continued until the platelets are at least 100,000/µL after the nadir.~Subjects will be recruited from the UC Davis Comprehensive Cancer Center or when they are admitted to UC Davis Children's Hospital.
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.