Clinical trial NCT01199822: 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
Overall status: COMPLETED
Phase: PHASE1
Conditions: Malignancy
Metastasis
Lead sponsor: Eli Lilly and Company
Sponsor class: INDUSTRY
First posted: 2010-09-13
Enrollment: 16
Sex: ALL
Minimum age (years): 20
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


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

Primary outcomes:
measure: Number of Participants With Adverse Events (AEs)
timeFrame: First dose to study completion up to 5.6 months
measure: Number of Participants With SAEs
timeFrame: First dose to study completion up to 5.6 months
measure: Number of Participants With a Dose- Limiting Toxicity (DLT) in Cycle 1
timeFrame: First dose through Cycle 1 (6 weeks/cycle)
measure: Maximum Concentration (Cmax) of Olaratumab Following Multiple Doses
timeFrame: Cycle 2: Pre-dose and up to 336 hours post-dose
Secondary outcomes:
measure: Area Under the Concentration of Olaratumab Versus Time Curve During One Dosing Interval (AUCτ) Following Multiple Doses
timeFrame: Cycle 2: Pre-dose and up to 336 hours post-dose
measure: Terminal Elimination Half-Life (t1/2) of Olaratumab
timeFrame: Cycle 2: Pre-dose and up to 336 hours post-dose
measure: Clearance of Olaratumab at Steady State (CLss)
timeFrame: Cycle 2: Pre-dose and up to 336 hours post-dose
measure: Volume of Distribution at Steady State (Vss)
timeFrame: Cycle 2: Pre-dose and up to 336 hours post-dose
measure: Number of Participants With Serum Anti-Olaratumab Antibody Assessment (Immunogenicity)
timeFrame: First dose to study completion up to 5.6 months
measure: Number of Participants With Treatment Related AEs
timeFrame: First dose to study completion up to 5.6 months
Other outcomes:
Locations:
city: Kashiwa
country: Japan
facility: ImClone Investigational Site
state: Chiba
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: