Description:
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.
Title
- Brief Title: 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
Clinical Trial IDs
- ORG STUDY ID:
15841
- SECONDARY ID:
I5B-MC-JGDN
- NCT ID:
NCT02677116
Conditions
Interventions
| Drug | Synonyms | Arms |
|---|
| Olaratumab | LY3012207 | Olaratumab Alone (Part A) |
| Doxorubicin | | Olaratumab + Doxorubicin (Part A) |
| Vincristine | | Olaratumab + Vincristine + Irinotecan (Part A) |
| Irinotecan | | Olaratumab + Vincristine + Irinotecan (Part A) |
| Ifosfamide | | Olaratumab + Ifosfamide (Part A) |
Purpose
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 two parts. In each part, a specific dose of olaratumab will be given for 21
days, followed by one of three standard chemotherapy regimens. Participants will only enroll
in one part.
Trial Arms
| Name | Type | Description | Interventions |
|---|
| Olaratumab Alone (Part A) | Experimental | Olaratumab administered intravenously (IV) on Days 1 and 8 for one cycle (21 days). | |
| Olaratumab + Doxorubicin (Part A) | Experimental | One cycle of olaratumab alone (administered IV on Days 1 and 8). For all subsequent cycles, olaratumab administered IV on Days 1 and 8 and doxorubicin administered IV on Days 1 and 2. All cycles are 21 days. Treatment will cease when discontinuation criterion is met. | |
| Olaratumab + Vincristine + Irinotecan (Part A) | Experimental | One cycle of olaratumab alone (administered IV on Days 1 and 8). For all subsequent cycles, olaratumab and vincristine administered IV on Days 1 and 8. Irinotecan administered IV on Days 1 through 5. All cycles are 21 days. Treatment will cease when discontinuation criterion is met. | - Olaratumab
- Vincristine
- Irinotecan
|
| Olaratumab + Ifosfamide (Part A) | Experimental | One cycle of olaratumab alone (administered IV on Days 1 and 8). For all subsequent cycles, olaratumab administered IV on Days 1 and 8 of each cycle. Ifosfamide administered IV on Days 1 though 5. All cycles are 21 days. Treatment will cease when discontinuation criterion is met. | |
| Olaratumab Alone (Part B) | Experimental | Olaratumab administered intravenously (IV) on Days 1 and 8 for one cycle (21 days). | |
| Olaratumab + Doxorubicin (Part B) | Experimental | One cycle of olaratumab alone (administered IV on Days 1 and 8). For all subsequent cycles, olaratumab administered IV on Days 1 and 8 and doxorubicin administered IV on Days 1 and 2. All cycles are 21 days. Treatment will cease when discontinuation criterion is met. | |
| Olaratumab + Vincristine + Irinotecan (Part B) | Experimental | One cycle of olaratumab alone (administered IV on Days 1 and 8). For all subsequent cycles, olaratumab and vincristine administered IV on Days 1 and 8. Irinotecan administered IV on Days 1 through 5. All cycles are 21 days. Treatment will cease when discontinuation criterion is met. | - Olaratumab
- Vincristine
- Irinotecan
|
| Olaratumab + Ifosfamide (Part B) | Experimental | One cycle of olaratumab alone (administered IV on Days 1 and 8). For all subsequent cycles, olaratumab administered IV on Days 1 and 8 of each cycle. Ifosfamide administered IV on Days 1 though 5. All cycles are 21 days. Treatment will cease when discontinuation criterion is met. | |
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 study drug, as appropriate.
- 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 study drug 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.
| Maximum Eligible Age: | 17 Years |
| Minimum Eligible Age: | N/A |
| Eligible Gender: | All |
| Healthy Volunteers: | No |
Primary Outcome Measures
| Measure: | Number of Participants with Olaratumab Dose Limiting Toxicities (DLTs) |
| Time Frame: | Cycle 1 in each arm (21 day cycle) |
| Safety Issue: | |
| Description: | |
Secondary Outcome Measures
| Measure: | Pharmacokinetics (PK): Maximum Concentration (Cmax) of Olaratumab |
| Time Frame: | Cycle 1 through Cycle 2 in each arm (21 day cycles; up to 42 days total) |
| Safety Issue: | |
| Description: | |
| Measure: | Pharmacokinetics (PK): Trough Serum Concentration (Cmin) of Olaratumab |
| Time Frame: | Cycle 1 through Cycle 5 in each arm (21 day cycles; up to 105 days total) |
| Safety Issue: | |
| Description: | |
| Measure: | Proportion of Participants With a Complete or Partial Response (Objective Response Rate [ORR]) |
| Time Frame: | Baseline to objective progression or start of new anti-cancer therapy (estimated up to 6 months) |
| Safety Issue: | |
| Description: | |
| Measure: | Progression Free Survival |
| Time Frame: | Baseline to objective progression or death from any cause (estimated up to 6 months) |
| Safety Issue: | |
| Description: | |
Details
| Phase: | Phase 1 |
| Primary Purpose: | Interventional |
| Overall Status: | Recruiting |
| Lead Sponsor: | Eli Lilly and Company |
Last Updated
September 2, 2017
