Study of the Safety and Pharmacokinetics of Olaratumab (IMC-3G3) in Japanese Participants With Solid Tumors
Primary Purpose
Malignancy, Metastasis
Status
Completed
Phase
Phase 1
Locations
Japan
Study Type
Interventional
Intervention
Olaratumab
Sponsored by
About this trial
This is an interventional treatment trial for Malignancy
Eligibility Criteria
Inclusion Criteria:
- Solid tumor that has been histopathologically or cytologically documented
- Advanced primary or recurrent solid tumor participants who has not responded to standard therapy or for whom no standard therapy is available
- Measurable or nonmeasurable lesions
- An Eastern Cooperative Oncology Group Performance Status score of 0-1
- Able to provide informed consent
- Has a life expectancy of >3 months
- Adequate hematologic function
- Adequate hepatic function
- Has adequate renal function
- Agrees to use adequate contraception for the duration of study participation and for at least 12 weeks after the last dose of study therapy
- Adequate recovery from recent surgery, chemotherapy, and radiation therapy (including palliative radiation therapy). At least 28 days (6 weeks for nitrosoureas or mitomycin C) must have elapsed from major surgery, prior chemotherapy, prior treatment with an investigational agent or device, or prior radiation therapy. For treatment with non-approved monoclonal antibodies, a minimum of 8 weeks must have elapsed
- Is willing to comply with study procedures until the End-of-Therapy visit
Exclusion Criteria:
- Received chemotherapy or therapeutic radiotherapy within 28 days (6 weeks for nitrosoureas or mitomycin C) prior to entering the study, or has ongoing side effects ≥ Grade 2 due to agents administered more than 28 days earlier
- Has undergone major surgery [example (e.g.), laparotomy, thoracotomy, removal of organ(s)] within 28 days prior to study entry
- Elective or planned surgery to be conducted during the trial
- Documented and/or symptomatic brain or leptomeningeal metastases (participants who are clinically stable [no symptoms during the 4 weeks prior to study entry] with an assessment that no further treatment [radiation, surgical excision, or administration of steroids] is required are permitted to enter the study)
Uncontrolled intercurrent illness including, but not limited to:
- Active infection requiring systemic antibiotic treatment excluding oral administration [≥Grade 3 National Cancer Institute - Common Terminology Criteria for Adverse Events [NCI-CTCAE Version (v) 4.02)]
- Congestive heart failure (Class III or IV per the New York Heart Association classification for heart disease)
- Angina pectoris, angioplasty, stenting, or myocardial infarction within 6 months
- Uncontrolled hypertension [systolic blood pressure >150 millimeters of mercury (mm Hg), diastolic blood pressure >95 mm Hg]
- Cardiac arrhythmia requiring treatment (NCI-CTCAE v4.02, or asymptomatic sustained ventricular tachycardia
- Peripheral neuropathy of any etiology ≥Grade 2 (NCI-CTCAE v4.02); or
- Any other serious uncontrolled medical disorder(s) in the opinion of the investigator
- Participated in clinical studies of non-approved experimental agents or procedures within 4 weeks prior to study for small molecules, or 8 weeks prior to study entry for non-approved monoclonal antibodies
- Received any previous treatment with agents targeting the platelet-derived growth factor (PDGF) or platelet-derived growth factor receptor (PDGFR), approved or non-approved
- Known allergy to any of the treatment components (IMC-3G3, histidine, glycine, sodium chloride, mannitol, or polysorbate)
- If female, is pregnant (confirmed by urine or serum pregnancy test) or lactating
- Known alcohol or drug dependency
- Hepatitis B virus (HBV) antigen-, hepatitis C virus (HCV) antibody-, or human immunodeficiency (HIV) antibody-positive [asymptomatic healthy carriers with detectable HBV-Deoxyribonucleic acid (DNA), HCV-Ribonucleic acid (RNA) may be enrolled into the trial]
- Assessed as inadequate for the study by the investigator
Sites / Locations
- ImClone Investigational Site
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Olaratumab
Arm Description
Outcomes
Primary Outcome Measures
Number of Participants With Adverse Events (AEs)
Data presented are the number of participants who experienced AEs of any grade and AEs of Grade ≥3 as determined by National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) Version (v) 4.02. A summary of serious adverse events (SAEs) and other non-serious AEs, regardless of causality, is located in the Reported Adverse Events module.
Number of Participants With SAEs
A summary of SAEs and other non-serious AEs, regardless of causality, is located in the Reported Adverse Events module.
Number of Participants With a Dose- Limiting Toxicity (DLT) in Cycle 1
A DLT is defined as 1 of the following events, if considered by the investigator to be definitely, probably, or possibly related to olaratumab: NCI-CTCAE v4.02 Grade 4 neutropenia lasting >7 days; NCI-CTCAE v4.02 Grade ≥3 thrombocytopenia with signs of bleeding or requiring platelet transfusions; NCI-CTCAE v4.02 Grade ≥3 neutropenia associated with fever; NCI-CTCAE v4.02 Grade 3 or 4 nonhematologic toxicity, excluding electrolyte abnormality; NCI-CTCAE v4.02 Grade ≥3 skin toxicity despite best preemptive and supportive care; and/or NCI-CTCAE v4.02 Grade ≥3 diarrhea, nausea, or vomiting despite best preemptive and supportive care.
Maximum Concentration (Cmax) of Olaratumab Following Multiple Doses
Secondary Outcome Measures
Area Under the Concentration of Olaratumab Versus Time Curve During One Dosing Interval (AUCτ) Following Multiple Doses
Terminal Elimination Half-Life (t1/2) of Olaratumab
t1/2 is the time it takes for the drug concentration in serum to decrease to half the value observed at the beginning of the time period.
Clearance of Olaratumab at Steady State (CLss)
CLss is the volume of plasma (or blood) from which the drug is completely removed, or cleared, in a given time at steady-state.
Volume of Distribution at Steady State (Vss)
Number of Participants With Serum Anti-Olaratumab Antibody Assessment (Immunogenicity)
Participants with Treatment Emergent (TE) anti-olaratumab antibodies were participants with a 4-fold increase (2 dilutions) increase over a positive baseline antibody titer or for a negative baseline titer, a participant with an increase from the baseline to a level of 1:20.
Number of Participants With Treatment Related AEs
Data presented are the number of participants who experienced a treatment related AE of any grade.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT01199822
Brief Title
Study of the Safety and Pharmacokinetics of Olaratumab (IMC-3G3) in Japanese Participants With Solid Tumors
Official Title
A Phase 1 Study Evaluating the Safety and Pharmacokinetic Profiles of IMC-3G3 Administered in a 2-week, or 3-week Schedule to Japanese Patients With Advanced Solid Tumors
Study Type
Interventional
2. Study Status
Record Verification Date
March 2017
Overall Recruitment Status
Completed
Study Start Date
September 2010 (undefined)
Primary Completion Date
January 2012 (Actual)
Study Completion Date
January 2012 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Eli Lilly and Company
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
Participants in this single-center, open-label, dose-escalation, Phase 1 study will initially receive intravenous (IV) olaratumab once every 2 weeks or on Days 1 and 8 every 3 weeks for 6 weeks (one cycle). After the first cycle, participants experiencing an overall response of complete response (CR), partial response (PR), or stable disease (SD) will continue to receive olaratumab at their cohort dose and schedule until there is evidence of progressive disease (PD), or until other withdrawal criteria are met.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Malignancy, Metastasis
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
16 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Olaratumab
Arm Type
Experimental
Intervention Type
Biological
Intervention Name(s)
Olaratumab
Other Intervention Name(s)
IMC-3G3, LY3012207
Intervention Description
Cohort 1 10 milligrams/kilogram (mg/kg) intravenously (IV) administered on Days 1 and 8, every 3 weeks; Cohort 2 20 mg/kg IV administered every 2 weeks; Cohort 3 15 mg/kg IV administered on Days 1 and 8, every 3 weeks
Primary Outcome Measure Information:
Title
Number of Participants With Adverse Events (AEs)
Description
Data presented are the number of participants who experienced AEs of any grade and AEs of Grade ≥3 as determined by National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) Version (v) 4.02. A summary of serious adverse events (SAEs) and other non-serious AEs, regardless of causality, is located in the Reported Adverse Events module.
Time Frame
First dose to study completion up to 5.6 months
Title
Number of Participants With SAEs
Description
A summary of SAEs and other non-serious AEs, regardless of causality, is located in the Reported Adverse Events module.
Time Frame
First dose to study completion up to 5.6 months
Title
Number of Participants With a Dose- Limiting Toxicity (DLT) in Cycle 1
Description
A DLT is defined as 1 of the following events, if considered by the investigator to be definitely, probably, or possibly related to olaratumab: NCI-CTCAE v4.02 Grade 4 neutropenia lasting >7 days; NCI-CTCAE v4.02 Grade ≥3 thrombocytopenia with signs of bleeding or requiring platelet transfusions; NCI-CTCAE v4.02 Grade ≥3 neutropenia associated with fever; NCI-CTCAE v4.02 Grade 3 or 4 nonhematologic toxicity, excluding electrolyte abnormality; NCI-CTCAE v4.02 Grade ≥3 skin toxicity despite best preemptive and supportive care; and/or NCI-CTCAE v4.02 Grade ≥3 diarrhea, nausea, or vomiting despite best preemptive and supportive care.
Time Frame
First dose through Cycle 1 (6 weeks/cycle)
Title
Maximum Concentration (Cmax) of Olaratumab Following Multiple Doses
Time Frame
Cycle 2: Pre-dose and up to 336 hours post-dose
Secondary Outcome Measure Information:
Title
Area Under the Concentration of Olaratumab Versus Time Curve During One Dosing Interval (AUCτ) Following Multiple Doses
Time Frame
Cycle 2: Pre-dose and up to 336 hours post-dose
Title
Terminal Elimination Half-Life (t1/2) of Olaratumab
Description
t1/2 is the time it takes for the drug concentration in serum to decrease to half the value observed at the beginning of the time period.
Time Frame
Cycle 2: Pre-dose and up to 336 hours post-dose
Title
Clearance of Olaratumab at Steady State (CLss)
Description
CLss is the volume of plasma (or blood) from which the drug is completely removed, or cleared, in a given time at steady-state.
Time Frame
Cycle 2: Pre-dose and up to 336 hours post-dose
Title
Volume of Distribution at Steady State (Vss)
Time Frame
Cycle 2: Pre-dose and up to 336 hours post-dose
Title
Number of Participants With Serum Anti-Olaratumab Antibody Assessment (Immunogenicity)
Description
Participants with Treatment Emergent (TE) anti-olaratumab antibodies were participants with a 4-fold increase (2 dilutions) increase over a positive baseline antibody titer or for a negative baseline titer, a participant with an increase from the baseline to a level of 1:20.
Time Frame
First dose to study completion up to 5.6 months
Title
Number of Participants With Treatment Related AEs
Description
Data presented are the number of participants who experienced a treatment related AE of any grade.
Time Frame
First dose to study completion up to 5.6 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
20 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Solid tumor that has been histopathologically or cytologically documented
Advanced primary or recurrent solid tumor participants who has not responded to standard therapy or for whom no standard therapy is available
Measurable or nonmeasurable lesions
An Eastern Cooperative Oncology Group Performance Status score of 0-1
Able to provide informed consent
Has a life expectancy of >3 months
Adequate hematologic function
Adequate hepatic function
Has adequate renal function
Agrees to use adequate contraception for the duration of study participation and for at least 12 weeks after the last dose of study therapy
Adequate recovery from recent surgery, chemotherapy, and radiation therapy (including palliative radiation therapy). At least 28 days (6 weeks for nitrosoureas or mitomycin C) must have elapsed from major surgery, prior chemotherapy, prior treatment with an investigational agent or device, or prior radiation therapy. For treatment with non-approved monoclonal antibodies, a minimum of 8 weeks must have elapsed
Is willing to comply with study procedures until the End-of-Therapy visit
Exclusion Criteria:
Received chemotherapy or therapeutic radiotherapy within 28 days (6 weeks for nitrosoureas or mitomycin C) prior to entering the study, or has ongoing side effects ≥ Grade 2 due to agents administered more than 28 days earlier
Has undergone major surgery [example (e.g.), laparotomy, thoracotomy, removal of organ(s)] within 28 days prior to study entry
Elective or planned surgery to be conducted during the trial
Documented and/or symptomatic brain or leptomeningeal metastases (participants who are clinically stable [no symptoms during the 4 weeks prior to study entry] with an assessment that no further treatment [radiation, surgical excision, or administration of steroids] is required are permitted to enter the study)
Uncontrolled intercurrent illness including, but not limited to:
Active infection requiring systemic antibiotic treatment excluding oral administration [≥Grade 3 National Cancer Institute - Common Terminology Criteria for Adverse Events [NCI-CTCAE Version (v) 4.02)]
Congestive heart failure (Class III or IV per the New York Heart Association classification for heart disease)
Angina pectoris, angioplasty, stenting, or myocardial infarction within 6 months
Uncontrolled hypertension [systolic blood pressure >150 millimeters of mercury (mm Hg), diastolic blood pressure >95 mm Hg]
Cardiac arrhythmia requiring treatment (NCI-CTCAE v4.02, or asymptomatic sustained ventricular tachycardia
Peripheral neuropathy of any etiology ≥Grade 2 (NCI-CTCAE v4.02); or
Any other serious uncontrolled medical disorder(s) in the opinion of the investigator
Participated in clinical studies of non-approved experimental agents or procedures within 4 weeks prior to study for small molecules, or 8 weeks prior to study entry for non-approved monoclonal antibodies
Received any previous treatment with agents targeting the platelet-derived growth factor (PDGF) or platelet-derived growth factor receptor (PDGFR), approved or non-approved
Known allergy to any of the treatment components (IMC-3G3, histidine, glycine, sodium chloride, mannitol, or polysorbate)
If female, is pregnant (confirmed by urine or serum pregnancy test) or lactating
Known alcohol or drug dependency
Hepatitis B virus (HBV) antigen-, hepatitis C virus (HCV) antibody-, or human immunodeficiency (HIV) antibody-positive [asymptomatic healthy carriers with detectable HBV-Deoxyribonucleic acid (DNA), HCV-Ribonucleic acid (RNA) may be enrolled into the trial]
Assessed as inadequate for the study by the investigator
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
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)
Organizational Affiliation
Eli Lilly and Company
Official's Role
Study Director
Facility Information:
Facility Name
ImClone Investigational Site
City
Kashiwa
State/Province
Chiba
Country
Japan
12. IPD Sharing Statement
Learn more about this trial
Study of the Safety and Pharmacokinetics of Olaratumab (IMC-3G3) in Japanese Participants With Solid Tumors
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