A Study of Olaratumab Alone and in Combination With Standard Chemotherapies in Children With Cancer

A Phase 1, Open-Label, Dose-Escalation Study of Olaratumab as a Single Agent and in Combination With Doxorubicin, Vincristine/Irinotecan, or High-Dose Ifosfamide in Pediatric Patients With Relapsed or Refractory Solid Tumors

The main purpose of this study is to evaluate the safety of different doses of olaratumab and to determine which dose should be used for future pediatric studies. The present study is open to children with advanced cancer or cancer that has spread to another part of the body. The study has three parts. In the first two parts, a specific dose of olaratumab will be given in 21 day cycles, followed by one of three standard chemotherapy regimens. In the third part, a specific dose of olaratumab will be given with one of three standard chemotherapy regimens in 21 day cycles. Participants will only enroll in one part.

Inclusion Criteria:

• The participant must have histological or cytological evidence of a diagnosis of solid tumor, excluding lymphomas and melanoma, but including central nervous system (CNS) tumors, that is relapsed or refractory, not be amenable to curative treatment.

• The participant has the presence of measurable and/or nonmeasurable but evaluable disease as defined by the Response Evaluation Criteria In Solid Tumors (RECIST Version 1.1). Response Assessment in Neuro-Oncology (RANO) Criteria or Macdonald Criteria should be used for CNS tumors.

• The participant has a Lansky (<16 years of age) or Karnofsky (≥16 years of age) performance score of at least 50.

• The participant has adequate hematologic, organ, and coagulation function ≤2 weeks (14 days) prior to first dose of study drug:

  • Absolute neutrophil count (ANC) ≥750 cubic millimeters (mm³)
  • Platelets ≥75,000/mm³
  • Hemoglobin ≥8 grams per deciliter (g/dL)
  • Total bilirubin (sum of conjugated + unconjugated) ≤1.5 x upper limit of normal (ULN) for age
  • Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤3.0 x ULN
  • Serum creatinine is based on age/gender
  • Adequate coagulation function as defined by International Normalized Ratio ≤1.5 or prothrombin time ≤1.5 x ULN, and partial thromboplastin time ≤1.5 x ULN

• Both female and male participants of child-bearing potential must agree to use highly effective contraceptive precautions during the trial and up to 3 months following the last dose of olaratumab, or longer for other study drugs according to their label.

• Participants must have fully recovered from the acute toxic effects of all prior anticancer therapies or must adhere to post-treatment conditions as follows:

  • Myelosuppressive chemotherapy
  • Hematopoietic growth factors
  • Biologic (anti-neoplastic agent)
  • Antibody therapy
  • Radiation
  • Stem cell infusion without traumatic brain injury
  • Corticosteroids

Exclusion Criteria:

• Have received treatment within 21 days of the initial dose of olaratumab with an investigational product or non-approved use of a drug or device or are concurrently enrolled in any other type of medical research judged not to be scientifically or medically compatible with this study.
• Participants that have had bone marrow or solid organ transplant are excluded.
• The participant has an active fungal, bacterial, and/or known severe viral infection including human immunodeficiency virus (HIV) or viral (A, B, or C) hepatitis (screening is not required).
• Female participants who are pregnant or breastfeeding are excluded.
• If the participant is to be enrolled in the doxorubicin combination arm, a left ventricular dysfunction (LVEF < 50%) or shortening fraction of <27% by echocardiogram (either multigated acquisition [MUGA] or echocardiogram [ECHO] are required, not both).
• Participants that have received prior anthracycline therapy if the participant is to be enrolled in the doxorubicin combination arm.