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

Eli Lilly and Company68 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Neoplasm Metastasis

Interventions

Eligibility

Sex: ALLMax age: 17 Years

Medical Language ↔ Plain English

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.

Locations (21)

Phoenix Childrens Hospital

Phoenix, Arizona, United States

Childrens Hospital of Los Angeles

Los Angeles, California, United States

University of California, San Francisco

San Francisco, California, United States

The Children's Hospital for Cancer and Blood Disorders

Aurora, Colorado, United States

Children's National Medical Center

Washington D.C., District of Columbia, United States

Sylvester Comprehensive Cancer Center

Miami, Florida, United States

Riley Hosptial for Children

Indianapolis, Indiana, United States

Dana Farber Cancer Institute

Boston, Massachusetts, United States

University of Minnesota Medical School

Minneapolis, Minnesota, United States

Children's Mercy Hospital

Kansas City, Missouri, United States

...and 11 more locations

Outcomes

Primary Outcomes

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.

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)

Secondary Outcomes

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

Pharmacokinetics (PK): Maximum serum concentration (Cmax) data of Olaratumab was reported from available sample data.

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 Concentration (Cmax) of Olaratumab Part B

PK: Maximum serum concentration (Cmax) data of Olaratumab was reported from available sample data.

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 Concentration (Cmax) of Olaratumab Part C

Pharmacokinetics (PK): Maximum serum concentration (Cmax) data of Olaratumab was reported from available sample data.

Time frame: 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

PK: Trough serum concentration (Cmin) of Olaratumab was reported. A sample was collected every other cycle from cycles 1, 2, 3-25.

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

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

PK: Trough serum concentration (Cmin) of Olaratumab was reported. A sample was collected every other cycle from cycles 1, 2, 3-25.

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

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

PK: Trough serum concentration (Cmin) of Olaratumab was reported. A sample was collected every other cycle from cycles 1, 2, 3-25.

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

Percentage of Participants With a Complete Response (CR) or Partial Response (PR) (Objective Response Rate [ORR])

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.

Time frame: Baseline to objective progression or start of new anti-cancer therapy (Up to 7 months)

Progression Free Survival (PFS)

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.

Time frame: Baseline to radiological disease progression or death from any cause (Up to 2 Years)

Percentage of Participants With Treatment Emergent (TE) Positive Anti-Olaratumab Antibodies

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.

Time frame: From Baseline to Study Completion (Up to 33 Months)