Phase 1
Completed N=16
Study of the Safety and Pharmacokinetics of Olaratumab (IMC-3G3) in Japanese Participants With Solid Tumors
Source: ClinicalTrials.gov NCT01199822 ↗Enrolled (actual)
16
Serious AEs
6.3%
Results posted
Apr 2017
Primary outcomePrimary: Number of Participants With Adverse Events (AEs) — 3; 7; 6; 1 participants
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.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Number of Participants With Adverse Events (AEs) |
3; 7; 6; 1; 1; 0 | — |
| PRIMARY Number of Participants With SAEs |
0; 1; 0 | — |
| PRIMARY Number of Participants With a Dose- Limiting Toxicity (DLT) in Cycle 1 |
0; 0; 0 | — |
| PRIMARY Maximum Concentration (Cmax) of Olaratumab Following Multiple Doses |
603; 1160; 921 | — |
| SECONDARY Area Under the Concentration of Olaratumab Versus Time Curve During One Dosing Interval (AUCτ) Following Multiple Doses |
123000 | — |
| SECONDARY Terminal Elimination Half-Life (t1/2) of Olaratumab |
NA; 7.33; 8.25 | — |
| SECONDARY Clearance of Olaratumab at Steady State (CLss) |
0.163 | — |
| SECONDARY Volume of Distribution at Steady State (Vss) |
— | — |
| SECONDARY Number of Participants With Serum Anti-Olaratumab Antibody Assessment (Immunogenicity) |
— | — |
| SECONDARY Number of Participants With Treatment Related AEs |
1; 6; 1; 0; 1; 0 | — |
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
Data sourced from ClinicalTrials.gov (NCT01199822). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.