Clinical Trials /

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

NCT02677116

Description:

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.

Related Conditions:
  • Central Nervous System Neoplasm
  • Malignant Solid Tumor
Recruiting Status:

Completed

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: A Study of Olaratumab Alone and in Combination With Standard Chemotherapies in Children With Cancer
  • Official Title: 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

Clinical Trial IDs

  • ORG STUDY ID: 15841
  • SECONDARY ID: I5B-MC-JGDN
  • NCT ID: NCT02677116

Conditions

  • Neoplasm Metastasis

Interventions

DrugSynonymsArms
OlaratumabLY3012207Olaratumab Alone (Part A)
DoxorubicinOlaratumab + Doxorubicin (Part A)
VincristineOlaratumab + Vincristine + Irinotecan (Part A)
IrinotecanOlaratumab + Vincristine + Irinotecan (Part A)
IfosfamideOlaratumab + Ifosfamide (Part A)

Purpose

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 two parts. In each part, a specific dose of olaratumab will be given for 21 days, followed by one of three standard chemotherapy regimens. Participants will only enroll in one part.

Trial Arms

NameTypeDescriptionInterventions
Olaratumab Alone (Part A)ExperimentalOlaratumab administered intravenously (IV) on Days 1 and 8 for one cycle (21 days).
  • Olaratumab
Olaratumab + Doxorubicin (Part A)ExperimentalOne cycle of olaratumab alone (administered IV on Days 1 and 8). For all subsequent cycles, olaratumab administered IV on Days 1 and 8 and doxorubicin administered IV on Days 1 and 2. All cycles are 21 days. Treatment will cease when discontinuation criterion is met.
  • Olaratumab
  • Doxorubicin
Olaratumab + Vincristine + Irinotecan (Part A)ExperimentalOne cycle of olaratumab alone (administered IV on Days 1 and 8). For all subsequent cycles, olaratumab and vincristine administered IV on Days 1 and 8. Irinotecan administered IV on Days 1 through 5. All cycles are 21 days. Treatment will cease when discontinuation criterion is met.
  • Olaratumab
  • Vincristine
  • Irinotecan
Olaratumab + Ifosfamide (Part A)ExperimentalOne cycle of olaratumab alone (administered IV on Days 1 and 8). For all subsequent cycles, olaratumab administered IV on Days 1 and 8 of each cycle. Ifosfamide administered IV on Days 1 though 5. All cycles are 21 days. Treatment will cease when discontinuation criterion is met.
  • Olaratumab
  • Ifosfamide
Olaratumab Alone (Part B)ExperimentalOlaratumab administered intravenously (IV) on Days 1 and 8 for one cycle (21 days).
  • Olaratumab
Olaratumab + Doxorubicin (Part B)ExperimentalOne cycle of olaratumab alone (administered IV on Days 1 and 8). For all subsequent cycles, olaratumab administered IV on Days 1 and 8 and doxorubicin administered IV on Days 1 and 2. All cycles are 21 days. Treatment will cease when discontinuation criterion is met.
  • Olaratumab
  • Doxorubicin
Olaratumab + Vincristine + Irinotecan (Part B)ExperimentalOne cycle of olaratumab alone (administered IV on Days 1 and 8). For all subsequent cycles, olaratumab and vincristine administered IV on Days 1 and 8. Irinotecan administered IV on Days 1 through 5. All cycles are 21 days. Treatment will cease when discontinuation criterion is met.
  • Olaratumab
  • Vincristine
  • Irinotecan
Olaratumab + Ifosfamide (Part B)ExperimentalOne cycle of olaratumab alone (administered IV on Days 1 and 8). For all subsequent cycles, olaratumab administered IV on Days 1 and 8 of each cycle. Ifosfamide administered IV on Days 1 though 5. All cycles are 21 days. Treatment will cease when discontinuation criterion is met.
  • Olaratumab
  • Ifosfamide

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 study drug, as appropriate.

          -  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 study drug 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.
      
Maximum Eligible Age:17 Years
Minimum Eligible Age:N/A
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Number of Participants with Olaratumab Dose Limiting Toxicities (DLTs)
Time Frame:Cycle 1 in each arm (21 day cycle)
Safety Issue:
Description:

Secondary Outcome Measures

Measure:Pharmacokinetics (PK): Maximum Concentration (Cmax) of Olaratumab
Time Frame:Cycle 1 through Cycle 2 in each arm (21 day cycles; up to 42 days total)
Safety Issue:
Description:
Measure:Pharmacokinetics (PK): Trough Serum Concentration (Cmin) of Olaratumab
Time Frame:Cycle 1 through Cycle 5 in each arm (21 day cycles; up to 105 days total)
Safety Issue:
Description:
Measure:Proportion of Participants With a Complete or Partial Response (Objective Response Rate [ORR])
Time Frame:Baseline to objective progression or start of new anti-cancer therapy (estimated up to 6 months)
Safety Issue:
Description:
Measure:Progression Free Survival
Time Frame:Baseline to objective progression or death from any cause (estimated up to 6 months)
Safety Issue:
Description:

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Eli Lilly and Company

Last Updated

September 2, 2017