A Study of Olaratumab Alone and in Combination With Standard Chemotherapies in Children With Cancer
Condition: Neoplasm Metastasis
MeSH terms: Neoplasm Metastasis
Intervention: Olaratumab; Doxorubicin; Vincristine; Irinotecan; Ifosfamide
Intervention description: Olaratumab administered IV.; Doxorubicin administered IV.; Vincristine administered IV.; Irinotecan administered IV.; Ifosfamide administered IV.
Intervention MeSH terms: Doxorubicin; Irinotecan; Vincristine; Ifosfamide; Olaratumab
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 68.0
Sex: All
Maximum age: 17 Years
Healthy volunteers: No

Summary:

      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.
    

Eligibility criteria:

        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.