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

Neoplasm Metastasis Clinical Trial

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 Details — Status: Completed

Administrative data

• NCT number: NCT02677116
• Other study ID #: 15841
• Secondary ID: I5B-MC-JGDN
• Status: Completed
• Phase: Phase 1
• Start date: August 29, 2016
• Est. completion date: April 3, 2019

Study information

• Verified date: June 1, 2019
• Source: Eli Lilly and Company
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 68
• Est. completion date: April 3, 2019
• Est. primary completion date: October 10, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A to 17 Years

Eligibility

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.

Related Conditions & MeSH terms

• Neoplasm Metastasis

Intervention

Drug:
• Olaratumab
Olaratumab administered IV.
• Doxorubicin
Doxorubicin administered IV.
• Vincristine
Vincristine administered IV.
• Irinotecan
Irinotecan administered IV.
• Ifosfamide
Ifosfamide administered IV.

Locations

Country	Name	City	State
Japan	National Cancer Center Hospital	Chuo-Ku	Tokyo
United States	The Children's Hospital for Cancer and Blood Disorders	Aurora	Colorado
United States	Dana Farber Cancer Institute	Boston	Massachusetts
United States	Levine Children's Hospital	Charlotte	North Carolina
United States	Mary Crowley Cancer Research Center	Dallas	Texas
United States	University of Texas Southwestern Medical Center at Dallas	Dallas	Texas
United States	Texas Childrens Hospital	Houston	Texas
United States	Riley Hosptial for Children	Indianapolis	Indiana
United States	Children's Mercy Hospital	Kansas City	Missouri
United States	Childrens Hospital of Los Angeles	Los Angeles	California
United States	St Jude Childrens Research Hospital	Memphis	Tennessee
United States	Sylvester Comprehensive Cancer Center	Miami	Florida
United States	University of Minnesota Medical School	Minneapolis	Minnesota
United States	Vanderbilt University Medical Center	Nashville	Tennessee
United States	Cohen Children's Medical Center	New Hyde Park	New York
United States	Memorial Sloan Kettering Cancer Center	New York	New York
United States	Phoenix Childrens Hospital	Phoenix	Arizona
United States	Primary Childrens Medical Center	Salt Lake City	Utah
United States	University of California, San Francisco	San Francisco	California
United States	Seattle Children's Hospital Research Foundation	Seattle	Washington
United States	Children's National Medical Center	Washington	District of Columbia

Sponsors (1)

Lead Sponsor	Collaborator
Eli Lilly and Company

Countries where clinical trial is conducted

United States,  Japan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Pharmacokinetics (PK): Maximum Concentration (Cmax) of Olaratumab Part A	Pharmacokinetics (PK): Maximum serum concentration (Cmax) data of Olaratumab was reported from available sample data.	Cycle 1, Day 8 and Cycle 2, Days 1 and 8: 1.25 hour (h), 2.5 h, 3.5h Postdose
Secondary	PK: Maximum Concentration (Cmax) of Olaratumab Part B	PK: Maximum serum concentration (Cmax) data of Olaratumab was reported from available sample data.	Cycle 1, Day 8 and Cycle 2, Days 1 and 8: 1.25 hour (h), 2.5 h, 3.5h Postdose
Secondary	PK: Maximum Concentration (Cmax) of Olaratumab Part C	Pharmacokinetics (PK): Maximum serum concentration (Cmax) data of Olaratumab was reported from available sample data.	Cycle 1, Days 1 and 8; Cycle 2, Days 1 and 8: 1.25 hour (h), 2.5 h, 3.5h Postdose
Secondary	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.	Cycles 1, 2, 3-25; Day 8: 336 Hours Postdose
Secondary	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.	Cycles 1, 2, 3-25; Day 8: 336 Hours Postdose
Secondary	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.	Cycles 1, 2, 3-25; Day 8: 336 Hours Postdose
Secondary	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.	Baseline to objective progression or start of new anti-cancer therapy (Up to 7 months)
Secondary	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.	Baseline to radiological disease progression or death from any cause (Up to 2 Years)
Secondary	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.	From Baseline to Study Completion (Up to 33 Months)

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