Safety Study of IHL-305 (Irinotecan Liposome Injection) to Treat Advanced Solid Tumors

Study Overview
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Brief Summary
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The purpose of this study is to determine whether IHL-305 (irinotecan liposome injection) is safe and effective in the treatment of advanced solid tumors.

Detailed Description
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This is a Phase I dose-escalation study of intravenous administration of IHL-305 in patients with advanced solid tumors. Patients will receive IHL-305 as an intravenous infusion over 60 minutes on Day 1 followed by a 27-day observation period for a total of 28 days (4 weeks) per cycle. Two patient populations will be evaluated separately; patients with UGT1A1*28 genotype homozygous wild-type (wt/wt) and heterozygous (wt/*28) variants as one group, and patients with UGT1A1*28 homozygous variant (*28/*28) as another group.

Official Title
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A Phase I Study of IHL-305 (Irinotecan Liposome Injection) in Patients With Advanced Solid Tumors

Conditions
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Cancer

Intervention / Treatment
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* Drug: IHL-305 (irinotecan liposome injection)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically confirmed malignant solid tumor and not a candidate for known regimens or protocol treatments of higher efficacy or priority Failed conventional therapy for their cancer or have a malignancy for which a conventional therapy does not exist Recovered from all acute adverse effects of prior therapies, excluding alopecia (hair loss) ECOG performance status of 0, 1, or 2 18 years of age or older Normal organ and bone marrow function as defined by: absolute neutrophil count greater than or equal to 1,500 cells/microliter platelets greater than or equal to 100,000 cells/microliter total bilirubin within normal institutional limits AST (SGOT)/ALT (SGPT) less than or equal to 2.5 x institutional upper limit of normal (ULN) or less than or equal to 5.0 x ULN in patients with liver metastases plasma creatinine less than or equal to 1.5 x institutional ULN OR creatinine clearance greater than or equal to 60 mL/min/1.73 m2 for patients with creatinine levels above institutional normal Ability to understand and the willingness to sign a written informed consent document Exclusion Criteria: Previously treated with irinotecan, or had chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study, or not recovered from adverse effects due to agents administered more than 4 weeks earlier Receiving any other investigational agent Known brain metastases History of allergic reactions attributed to compounds of similar chemical composition to IHL-305 Concurrent serious infections (i.e., requiring an intravenous antibiotic) Pregnant women or women of childbearing potential and not using methods to avoid pregnancy; a negative pregnancy test (urine or serum) must be documented at baseline for women of childbearing potential; no breast-feeding while on study. Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, unstable angina pectoris, or psychiatric illness/social situations that would limit compliance with study requirements Significant cardiac disease including heart failure that meets New York Heart Association (NYHA) class III and IV definitions; history of myocardial infarction within one year of study entry; uncontrolled dysrhythmias; or poorly controlled angina. History of serious ventricular arrhythmia (ventricular tachycardia [VT] or ventricular fibrillation [VF], greater than or equal to 3 beats in a row); QTc greater than or equal to 450 msec for men and 470 msec for women; or left ventricular ejection fraction (LVEF) less than or equal to 40% by multi-gated acquisition scan (MUGA).

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: IHL-305 (irinotecan liposome injection)|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of dose-limiting toxicity within 28 days of treatment administration for patients with UGT1A1*28 genotype (wt/wt and wt/*28) |  |  | 
| determination of maximum tolerated dose (MTD) and recommended Phase 2 dose for patients with UGT1A1*28 genotype (wt/wt and wt/*28) |  |  | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Tumor shrinkage per Response Evaluation Criteria in Solid Tumors (RECIST) every 8 weeks/2 cycles while receiving study drug for patients with UGT1A1*28 genotype (wt/wt and wt/*28) |  |  | 
| limited pharmacokinetics (PK) for patients with UGT1A1*28 genotype (wt/wt and wt/*28) |  |  | 
| limited incidence and severity of adverse events (AEs) and PK for UGT1A1 homozygous (*28/*28) patients |  |  | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Cancer, Advanced Solid Tumor, Oncology