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

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

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.

Study Overview

• Status: Completed
• Conditions: Cancer
• Intervention / Treatment: Drug: IHL-305 (irinotecan liposome injection)

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Anticipated): 40
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Sarah Cannon Cancer Center
    • Nashville, Tennessee, United States, 37232-6307
      • Vanderbilt-Ingram Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Histologically confirmed malignant solid tumor and not a candidate for known regimens or protocol treatments of higher efficacy or priority
2. Failed conventional therapy for their cancer or have a malignancy for which a conventional therapy does not exist
3. Recovered from all acute adverse effects of prior therapies, excluding alopecia (hair loss)
4. ECOG performance status of 0, 1, or 2
5. 18 years of age or older

6. 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
7. Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria:

1. 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
2. Receiving any other investigational agent
3. Known brain metastases
4. History of allergic reactions attributed to compounds of similar chemical composition to IHL-305
5. Concurrent serious infections (i.e., requiring an intravenous antibiotic)
6. 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.
7. 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
8. 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.
9. 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).

Study Plan

How is the study designed?

Design Details

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
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
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

Collaborators and Investigators

• Sponsor: Yakult Honsha Co., LTD
• Investigators: Principal Investigator: Mace L Rothenberg, M.D., Vanderbilt University

Study record dates

Study Major Dates

• Study Start: September 1, 2006
• Study Completion: June 1, 2011

Study Registration Dates

• First Submitted: August 11, 2006
• First Submitted That Met QC Criteria: August 11, 2006
• First Posted (Estimate): August 15, 2006

Study Record Updates

• Last Update Posted (Actual): July 5, 2019
• Last Update Submitted That Met QC Criteria: July 2, 2019
• Last Verified: July 1, 2019

More Information

Terms related to this study

• Keywords: Cancer; Oncology; Advanced Solid Tumor
• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Topoisomerase Inhibitors; Topoisomerase I Inhibitors; Irinotecan
• Other Study ID Numbers: IHL-PRT001