Clinical Trial: NCT02677116 - My Cancer Genome

NCT02677116

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.

Related Conditions:

Central Nervous System Neoplasm
Malignant Solid Tumor

Recruiting Status:

Completed

Phase:

Phase 1

URL:

https://clinicaltrials.gov/show/NCT02677116

Trial Eligibility

Document

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

Neoplasm Metastasis

Interventions

Drug	Synonyms	Arms
Olaratumab	LY3012207	Olaratumab + Doxorubicin (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

Trial Arms

Name	Type	Description	Interventions
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.	Olaratumab 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.	Olaratumab Vincristine 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.	Olaratumab 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.	Olaratumab 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.	Olaratumab Vincristine 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.	Olaratumab Doxorubicin 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.	Olaratumab 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.	Olaratumab Vincristine 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.	Olaratumab Ifosfamide

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.

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

Secondary Outcome Measures

Measure:	Pharmacokinetics (PK): Maximum Concentration (Cmax) of Olaratumab Part A
Time Frame:	Cycle 1, Day 8 and Cycle 2, Days 1 and 8: 1.25 hour (h), 2.5 h, 3.5h Postdose
Safety Issue:
Description:	Pharmacokinetics (PK): Maximum serum concentration (Cmax) data of Olaratumab was reported from available sample data.

Measure:	PK: Maximum Concentration (Cmax) of Olaratumab Part B
Time Frame:	Cycle 1, Day 8 and Cycle 2, Days 1 and 8: 1.25 hour (h), 2.5 h, 3.5h Postdose
Safety Issue:
Description:	PK: Maximum serum concentration (Cmax) data of Olaratumab was reported from available sample data.

Measure:	PK: Maximum Concentration (Cmax) of Olaratumab Part C
Time Frame:	Cycle 1, Days 1 and 8; Cycle 2, Days 1 and 8: 1.25 hour (h), 2.5 h, 3.5h Postdose
Safety Issue:
Description:	Pharmacokinetics (PK): Maximum serum concentration (Cmax) data of Olaratumab was reported from available sample data.

Measure:	PK: Trough Serum Minimum Concentration (Cmin) of Olaratumab Part A
Time Frame:	Cycles 1, 2, 3-25; Day 8: 336 Hours Postdose
Safety Issue:
Description:	PK: Trough serum concentration (Cmin) of Olaratumab was reported. A sample was collected every other cycle from cycles 1, 2, 3-25.

Measure:	PK: Trough Serum Minimum Concentration (Cmin) of Olaratumab Part B
Time Frame:	Cycles 1, 2, 3-25; Day 8: 336 Hours Postdose
Safety Issue:
Description:	PK: Trough serum concentration (Cmin) of Olaratumab was reported. A sample was collected every other cycle from cycles 1, 2, 3-25.

Measure:	PK: Trough Serum Minimum Concentration (Cmin) of Olaratumab Part C
Time Frame:	Cycles 1, 2, 3-25; Day 8: 336 Hours Postdose
Safety Issue:
Description:	PK: Trough serum concentration (Cmin) of Olaratumab was reported. A sample was collected every other cycle from cycles 1, 2, 3-25.

Measure:	Percentage of Participants With a Complete Response (CR) or Partial Response (PR) (Objective Response Rate [ORR])
Time Frame:	Baseline to objective progression or start of new anti-cancer therapy (Up to 7 months)
Safety Issue:
Description:	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.

Measure:	Progression Free Survival (PFS)
Time Frame:	Baseline to radiological disease progression or death from any cause (Up to 2 Years)
Safety Issue:
Description:	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.

Measure:	Percentage of Participants With Treatment Emergent (TE) Positive Anti-Olaratumab Antibodies
Time Frame:	From Baseline to Study Completion (Up to 33 Months)
Safety Issue:
Description:	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.

Details

Phase:	Phase 1
Primary Purpose:	Interventional
Overall Status:	Completed
Lead Sponsor:	Eli Lilly and Company

Last Updated

May 20, 2020

Clinical Trials /

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