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

NCT02677116 | Completed Phase 1 Results

• 2 other identifiers: 15841I5B-MC-JGDN
• Study Type: interventional
• Target: 68
• Locations: 2 countries
• Sites: 21

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.

Conditions

Neoplasm Metastasis

Outcome Measures

Primary Outcomes (1)

• Number of Participants With Olaratumab Dose Limiting Toxicities (DLTs)

  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.

  Parts A and B: Cycle 1 through Cycle 2 in each arm (21-day cycle); Part C: Cycle 1 only (21-day cycle)

Secondary Outcomes (9)

• Pharmacokinetics (PK): Maximum Concentration (Cmax) of Olaratumab Part A

  Cycle 1, Day 8 and Cycle 2, Days 1 and 8: 1.25 hour (h), 2.5 h, 3.5h Postdose

• PK: Maximum Concentration (Cmax) of Olaratumab Part B

  Cycle 1, Day 8 and Cycle 2, Days 1 and 8: 1.25 hour (h), 2.5 h, 3.5h Postdose

• PK: Maximum Concentration (Cmax) of Olaratumab Part C

  Cycle 1, Days 1 and 8; Cycle 2, Days 1 and 8: 1.25 hour (h), 2.5 h, 3.5h Postdose

• PK: Trough Serum Minimum Concentration (Cmin) of Olaratumab Part A

  Cycles 1, 2, 3-25; Day 8: 336 Hours Postdose

• PK: Trough Serum Minimum Concentration (Cmin) of Olaratumab Part B

  Cycles 1, 2, 3-25; Day 8: 336 Hours Postdose

Study Arms (9)

Olaratumab + Doxorubicin (Part A)

EXPERIMENTAL

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; Drug: Doxorubicin

Olaratumab + Vincristine + Irinotecan (Part A)

EXPERIMENTAL

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; Drug: Vincristine; Drug: Irinotecan

Olaratumab + Ifosfamide (Part A)

EXPERIMENTAL

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; Drug: Ifosfamide

Olaratumab + Doxorubicin (Part B)

EXPERIMENTAL

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; Drug: Doxorubicin

Olaratumab + Vincristine + Irinotecan (Part B)

EXPERIMENTAL

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; Drug: Vincristine; Drug: Irinotecan

Olaratumab + Ifosfamide (Part B)

EXPERIMENTAL

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; Drug: Doxorubicin; Drug: Ifosfamide

Olaratumab + Doxorubicin (Part C)

EXPERIMENTAL

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; Drug: Doxorubicin

Olaratumab + Vincristine + Irinotecan (Part C)

EXPERIMENTAL

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; Drug: Vincristine; Drug: Irinotecan

Olaratumab + Ifosfamide (Part C)

EXPERIMENTAL

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; Drug: Ifosfamide

Interventions

Olaratumab DRUG

Olaratumab administered IV.

Also known as: LY3012207

Olaratumab + Doxorubicin (Part A); Olaratumab + Doxorubicin (Part B); Olaratumab + Doxorubicin (Part C); Olaratumab + Ifosfamide (Part A); Olaratumab + Ifosfamide (Part B); Olaratumab + Ifosfamide (Part C); Olaratumab + Vincristine + Irinotecan (Part A); Olaratumab + Vincristine + Irinotecan (Part B); Olaratumab + Vincristine + Irinotecan (Part C)

Doxorubicin DRUG

Doxorubicin administered IV.

Olaratumab + Doxorubicin (Part A); Olaratumab + Doxorubicin (Part B); Olaratumab + Doxorubicin (Part C); Olaratumab + Ifosfamide (Part B)

Vincristine DRUG

Vincristine administered IV.

Olaratumab + Vincristine + Irinotecan (Part A); Olaratumab + Vincristine + Irinotecan (Part B); Olaratumab + Vincristine + Irinotecan (Part C)

Irinotecan DRUG

Irinotecan administered IV.

Olaratumab + Vincristine + Irinotecan (Part A); Olaratumab + Vincristine + Irinotecan (Part B); Olaratumab + Vincristine + Irinotecan (Part C)

Ifosfamide DRUG

Ifosfamide administered IV.

Olaratumab + Ifosfamide (Part A); Olaratumab + Ifosfamide (Part B); Olaratumab + Ifosfamide (Part C)

Eligibility Criteria

• Age: Up to 17 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Eli Lilly and Company: lead

Study Sites (21)

Phoenix Childrens Hospital

Phoenix, Arizona, 85016, United States

Location

Childrens Hospital of Los Angeles

Los Angeles, California, 90027, United States

Location

University of California, San Francisco

San Francisco, California, 94158, United States

Location

The Children's Hospital for Cancer and Blood Disorders

Aurora, Colorado, 80045, United States

Location

Children's National Medical Center

Washington D.C., District of Columbia, 20010-2970, United States

Location

Sylvester Comprehensive Cancer Center

Miami, Florida, 33136, United States

Location

Riley Hosptial for Children

Indianapolis, Indiana, 46202, United States

Location

Dana Farber Cancer Institute

Boston, Massachusetts, 02115, United States

Location

University of Minnesota Medical School

Minneapolis, Minnesota, 55455, United States

Location

Children's Mercy Hospital

Kansas City, Missouri, 64108, United States

Location

Cohen Children's Medical Center

New Hyde Park, New York, 11040, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

Levine Children's Hospital

Charlotte, North Carolina, 28203, United States

Location

St Jude Childrens Research Hospital

Memphis, Tennessee, 38105, United States

Location

Vanderbilt University Medical Center

Nashville, Tennessee, 37232-6307, United States

Location

Mary Crowley Cancer Research Center

Dallas, Texas, 75230, United States

Location

University of Texas Southwestern Medical Center at Dallas

Dallas, Texas, 75235, United States

Location

Texas Childrens Hospital

Houston, Texas, 77030, United States

Location

Primary Childrens Medical Center

Salt Lake City, Utah, 84132, United States

Location

Seattle Children's Hospital Research Foundation

Seattle, Washington, 98105, United States

Location

National Cancer Center Hospital

Chuo-Ku, Tokyo, 104-0045, Japan

Location

Related Links

• Click here for more information about this study: A Study of Olaratumab Alone and in Combination With Standard Chemotherapies in Children With Cancer

MeSH Terms

Conditions

Neoplasm Metastasis

Interventions

olaratumab; Doxorubicin; Vincristine; Irinotecan; Ifosfamide

Condition Hierarchy (Ancestors)

Neoplastic Processes; Neoplasms; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates; Vinca Alkaloids; Secologanin Tryptamine Alkaloids; Indole Alkaloids; Alkaloids; Heterocyclic Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Indolizidines; Indolizines; Camptothecin; Cyclophosphamide; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Phosphoramides; Organophosphorus Compounds; Oxazines; Heterocyclic Compounds, 1-Ring

Results Point of Contact

• Title: Chief Medical Officer
• Organization: Eli Lilly and Company

ClinicalTrials.gov@lilly.com

800-545-5979

Study Officials

• 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 DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: GT60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 29, 2016
• First Posted: February 9, 2016
• Study Start: August 29, 2016
• Primary Completion: October 10, 2018
• Study Completion: April 3, 2019
• Last Updated: May 20, 2020
• Results First Posted: May 20, 2020

Record last verified: 2019-06-01

Data Sharing

• IPD Sharing: Will not share

Locations

JP (1); US (20)