Clinical trial NCT02677116: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Neoplasm Metastasis
Lead sponsor: Eli Lilly and Company
Sponsor class: INDUSTRY
First posted: 2016-02-09
Enrollment: 68
Sex: ALL
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


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.

Primary outcomes:
measure: Number of Participants With Olaratumab Dose Limiting Toxicities (DLTs)
timeFrame: 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:
measure: Pharmacokinetics (PK): Maximum Concentration (Cmax) of Olaratumab Part A
timeFrame: Cycle 1, Day 8 and Cycle 2, Days 1 and 8: 1.25 hour (h), 2.5 h, 3.5h Postdose
measure: PK: Maximum Concentration (Cmax) of Olaratumab Part B
timeFrame: Cycle 1, Day 8 and Cycle 2, Days 1 and 8: 1.25 hour (h), 2.5 h, 3.5h Postdose
measure: PK: Maximum Concentration (Cmax) of Olaratumab Part C
timeFrame: Cycle 1, Days 1 and 8; Cycle 2, Days 1 and 8: 1.25 hour (h), 2.5 h, 3.5h Postdose
measure: PK: Trough Serum Minimum Concentration (Cmin) of Olaratumab Part A
timeFrame: Cycles 1, 2, 3-25; Day 8: 336 Hours Postdose
measure: PK: Trough Serum Minimum Concentration (Cmin) of Olaratumab Part B
timeFrame: Cycles 1, 2, 3-25; Day 8: 336 Hours Postdose
measure: PK: Trough Serum Minimum Concentration (Cmin) of Olaratumab Part C
timeFrame: Cycles 1, 2, 3-25; Day 8: 336 Hours Postdose
measure: Percentage of Participants With a Complete Response (CR) or Partial Response (PR) (Objective Response Rate [ORR])
timeFrame: Baseline to objective progression or start of new anti-cancer therapy (Up to 7 months)
measure: Progression Free Survival (PFS)
timeFrame: Baseline to radiological disease progression or death from any cause (Up to 2 Years)
measure: Percentage of Participants With Treatment Emergent (TE) Positive Anti-Olaratumab Antibodies
timeFrame: From Baseline to Study Completion (Up to 33 Months)
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Phoenix Childrens Hospital
state: Arizona
city: Los Angeles
country: United States
facility: Childrens Hospital of Los Angeles
state: California
city: San Francisco
country: United States
facility: University of California, San Francisco
state: California
city: Aurora
country: United States
facility: The Children's Hospital for Cancer and Blood Disorders
state: Colorado
city: Washington
country: United States
facility: Children's National Medical Center
state: District of Columbia
city: Miami
country: United States
facility: Sylvester Comprehensive Cancer Center
state: Florida
city: Indianapolis
country: United States
facility: Riley Hosptial for Children
state: Indiana
city: Boston
country: United States
facility: Dana Farber Cancer Institute
state: Massachusetts
city: Minneapolis
country: United States
facility: University of Minnesota Medical School
state: Minnesota
city: Kansas City
country: United States
facility: Children's Mercy Hospital
state: Missouri
city: New Hyde Park
country: United States
facility: Cohen Children's Medical Center
state: New York
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: Charlotte
country: United States
facility: Levine Children's Hospital
state: North Carolina
city: Memphis
country: United States
facility: St Jude Childrens Research Hospital
state: Tennessee
city: Nashville
country: United States
facility: Vanderbilt University Medical Center
state: Tennessee
city: Dallas
country: United States
facility: Mary Crowley Cancer Research Center
state: Texas
city: Dallas
country: United States
facility: University of Texas Southwestern Medical Center at Dallas
state: Texas
city: Houston
country: United States
facility: Texas Childrens Hospital
state: Texas
city: Salt Lake City
country: United States
facility: Primary Childrens Medical Center
state: Utah
city: Seattle
country: United States
facility: Seattle Children's Hospital Research Foundation
state: Washington
city: Chuo-Ku
country: Japan
facility: National Cancer Center Hospital
state: Tokyo
Study officials:
affiliation: Eli Lilly and Company
name: 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)
role: STUDY_DIRECTOR
References: