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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02677116
Recruitment Status : Completed
First Posted : February 9, 2016
Results First Posted : May 20, 2020
Last Update Posted : May 20, 2020
Sponsor:
Information provided by (Responsible Party):
Eli Lilly and Company

Brief 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.

Condition or disease Intervention/treatment Phase
Neoplasm Metastasis Drug: Olaratumab Drug: Doxorubicin Drug: Vincristine Drug: Irinotecan Drug: Ifosfamide Phase 1

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 68 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : August 29, 2016
Actual Primary Completion Date : October 10, 2018
Actual Study Completion Date : April 3, 2019

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Olaratumab + Doxorubicin (Part A)

Cycle 1: Olaratumab 15 mg/kg was administered IV Days 1 and 8.

Cycle 2 and beyond: Olaratumab 15 mg/kg administered IV on Days 1 and 8 and doxorubicin administered IV on Days 1 and 2. Treatment will cease when discontinuation criterion is met.

All cycles are 21 days.

Drug: Olaratumab
Olaratumab administered IV.
Other Name: LY3012207

Drug: Doxorubicin
Doxorubicin administered IV.

Experimental: Olaratumab + Vincristine + Irinotecan (Part A)

Cycle 1: Olaratumab 15 mg/kg was administered IV Days 1 and 8.

Cycle 2 and beyond: Olaratumab 15 mg/kg and vincristine administered IV on Days 1 and 8. Irinotecan administered IV on Days 1 through 5. Treatment will cease when discontinuation criterion is met.

All cycles are 21 days.

Drug: Olaratumab
Olaratumab administered IV.
Other Name: LY3012207

Drug: Vincristine
Vincristine administered IV.

Drug: Irinotecan
Irinotecan administered IV.

Experimental: Olaratumab + Ifosfamide (Part A)

Cycle 1: Olaratumab 15 mg/kg was administered IV Days 1 and 8.

Cycle 2 and beyond: Olaratumab 15 mg/kg administered IV on Days 1 and 8 of each cycle. Ifosfamide administered IV on Days 1 through 5. Treatment will cease when discontinuation criterion is met.

All cycles are 21 days.

Drug: Olaratumab
Olaratumab administered IV.
Other Name: LY3012207

Drug: Ifosfamide
Ifosfamide administered IV.

Experimental: Olaratumab + Doxorubicin (Part B)

Cycle 1: Olaratumab 20 mg/kg was administered IV Days 1 and 8.

Cycle 2 and beyond: Olaratumab 20 mg/kg administered IV on Days 1 and 8 and doxorubicin administered IV on Days 1 and 2. Treatment will cease when discontinuation criterion is met.

All cycles are 21 days.

Drug: Olaratumab
Olaratumab administered IV.
Other Name: LY3012207

Drug: Doxorubicin
Doxorubicin administered IV.

Experimental: Olaratumab + Vincristine + Irinotecan (Part B)

Cycle 1: Olaratumab 20 mg/kg was administered IV Days 1 and 8.

Cycle 2 and beyond: Olaratumab 20 mg/kg and vincristine administered IV on Days 1 and 8. Irinotecan administered IV on Days 1 through 5. Treatment will cease when discontinuation criterion is met.

All cycles are 21 days.

Drug: Olaratumab
Olaratumab administered IV.
Other Name: LY3012207

Drug: Vincristine
Vincristine administered IV.

Drug: Irinotecan
Irinotecan administered IV.

Experimental: Olaratumab + Ifosfamide (Part B)

Cycle 1: Olaratumab 20 mg/kg was administered IV Days 1 and 8.

Cycle 2 and beyond: Olaratumab 20 mg/kg administered IV on Days 1 and 8 of each cycle. Ifosfamide administered IV on Days 1 through 5. Treatment will cease when discontinuation criterion is met.

All cycles are 21 days.

Drug: Olaratumab
Olaratumab administered IV.
Other Name: LY3012207

Drug: Doxorubicin
Doxorubicin administered IV.

Drug: Ifosfamide
Ifosfamide administered IV.

Experimental: Olaratumab + Doxorubicin (Part C)

Cycle 1 and beyond: Olaratumab 20 mg/kg administered IV on Days 1 and 8 and doxorubicin administered IV on Days 1 and 2. Treatment will cease when discontinuation criterion is met.

All cycles are 21 days.

Drug: Olaratumab
Olaratumab administered IV.
Other Name: LY3012207

Drug: Doxorubicin
Doxorubicin administered IV.

Experimental: Olaratumab + Vincristine + Irinotecan (Part C)

Cycle 1 and beyond: Olaratumab 20 mg/kg and vincristine administered IV on Days 1 and 8. Irinotecan administered IV on Days 1 through 5. Treatment will cease when discontinuation criterion is met.

All cycles are 21 days.

Drug: Olaratumab
Olaratumab administered IV.
Other Name: LY3012207

Drug: Vincristine
Vincristine administered IV.

Drug: Irinotecan
Irinotecan administered IV.

Experimental: Olaratumab + Ifosfamide (Part C)

Cycle 1 and beyond: Olaratumab 20 mg/kg administered IV on Days 1 and 8 of each cycle. Ifosfamide administered IV on Days 1 through 5. Treatment will cease when discontinuation criterion is met.

All cycles are 21 days.

Drug: Olaratumab
Olaratumab administered IV.
Other Name: LY3012207

Drug: Ifosfamide
Ifosfamide administered IV.




Primary Outcome Measures :
  1. Number of Participants With Olaratumab Dose Limiting Toxicities (DLTs) [ Time Frame: Parts A and B: Cycle 1 through Cycle 2 in each arm (21-day cycle); Part C: Cycle 1 only (21-day cycle) ]
    A dose limiting toxicity (DLT) was defined as an adverse event (AE) during the first 21 days that was possibly related to the study drug and fulfilled any of the following criteria using the National Cancer Institute's (NCI) Common Terminology Criteria for Adverse Events (CTCAE), Version 4.0: CTCAE Grade 3 nonhematologic toxicity, grade 4 neutropenia that lasted longer than 2 weeks, grade ≥3 thrombocytopenia complicated by hemorrhage, and any hematologic toxicity that caused a cycle delay of >14 days.


Secondary Outcome Measures :
  1. Pharmacokinetics (PK): Maximum Concentration (Cmax) of Olaratumab Part A [ Time Frame: Cycle 1, Day 8 and Cycle 2, Days 1 and 8: 1.25 hour (h), 2.5 h, 3.5h Postdose ]
    Pharmacokinetics (PK): Maximum serum concentration (Cmax) data of Olaratumab was reported from available sample data.

  2. PK: Maximum Concentration (Cmax) of Olaratumab Part B [ Time Frame: Cycle 1, Day 8 and Cycle 2, Days 1 and 8: 1.25 hour (h), 2.5 h, 3.5h Postdose ]
    PK: Maximum serum concentration (Cmax) data of Olaratumab was reported from available sample data.

  3. PK: Maximum Concentration (Cmax) of Olaratumab Part C [ Time Frame: Cycle 1, Days 1 and 8; Cycle 2, Days 1 and 8: 1.25 hour (h), 2.5 h, 3.5h Postdose ]
    Pharmacokinetics (PK): Maximum serum concentration (Cmax) data of Olaratumab was reported from available sample data.

  4. PK: Trough Serum Minimum Concentration (Cmin) of Olaratumab Part A [ Time Frame: Cycles 1, 2, 3-25; Day 8: 336 Hours Postdose ]
    PK: Trough serum concentration (Cmin) of Olaratumab was reported. A sample was collected every other cycle from cycles 1, 2, 3-25.

  5. PK: Trough Serum Minimum Concentration (Cmin) of Olaratumab Part B [ Time Frame: Cycles 1, 2, 3-25; Day 8: 336 Hours Postdose ]
    PK: Trough serum concentration (Cmin) of Olaratumab was reported. A sample was collected every other cycle from cycles 1, 2, 3-25.

  6. PK: Trough Serum Minimum Concentration (Cmin) of Olaratumab Part C [ Time Frame: Cycles 1, 2, 3-25; Day 8: 336 Hours Postdose ]
    PK: Trough serum concentration (Cmin) of Olaratumab was reported. A sample was collected every other cycle from cycles 1, 2, 3-25.

  7. Percentage of Participants With a Complete Response (CR) or Partial Response (PR) (Objective Response Rate [ORR]) [ Time Frame: Baseline to objective progression or start of new anti-cancer therapy (Up to 7 months) ]
    Objective Response Rate (ORR) is the percentage of participants achieving a confirmed best overall tumor response of CR or PR. According to RECIST v1.1, PR defined as a >30% decrease in the sum of the longest diameters (LD) of the target lesions, taking as reference the baseline sum of the LD; CR was defined as the disappearance of all target and non-target lesions.

  8. Progression Free Survival (PFS) [ Time Frame: Baseline to radiological disease progression or death from any cause (Up to 2 Years) ]
    Progression-free survival (PFS) is defined as the time from baseline to the first date of radiological disease progression or death due to any cause. Progressive disease (PD) according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 is defined as at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (including the baseline sum if that is the smallest). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 millimeters (mm). The appearance of one or more new lesions is also considered progression. If participant started new treatment before PD, the participant was censored at the date of last tumor assessment prior to new therapy. If treatment was discontinued for reasons other than PD and no further assessment, censoring occurred at last tumor assessment.

  9. Percentage of Participants With Treatment Emergent (TE) Positive Anti-Olaratumab Antibodies [ Time Frame: From Baseline to Study Completion (Up to 33 Months) ]
    Percentage of participants with a TE positive anti-olaratumab antibodies defined as a participant with a 4-fold (2 dilutions) increase over a positive baseline antibody titer.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   up to 17 Years   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02677116


Locations
Show Show 21 study locations
Sponsors and Collaborators
Eli Lilly and Company
Investigators
Layout table for investigator information
Study Director: Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST) Eli Lilly and Company
  Study Documents (Full-Text)

Documents provided by Eli Lilly and Company:
Study Protocol  [PDF] February 14, 2018
Statistical Analysis Plan  [PDF] November 26, 2018

Additional Information:
Layout table for additonal information
Responsible Party: Eli Lilly and Company
ClinicalTrials.gov Identifier: NCT02677116    
Other Study ID Numbers: 15841
I5B-MC-JGDN ( Other Identifier: Eli Lilly and Company )
First Posted: February 9, 2016    Key Record Dates
Results First Posted: May 20, 2020
Last Update Posted: May 20, 2020
Last Verified: June 1, 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Additional relevant MeSH terms:
Layout table for MeSH terms
Neoplasm Metastasis
Neoplastic Processes
Neoplasms
Pathologic Processes
Doxorubicin
Irinotecan
Vincristine
Ifosfamide
Olaratumab
Antibiotics, Antineoplastic
Antineoplastic Agents
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Topoisomerase I Inhibitors
Antineoplastic Agents, Phytogenic
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Antineoplastic Agents, Alkylating
Alkylating Agents