A Study of PEP02 in Combination With 5-fluorouracil (5-FU) and Leucovorin (LV) in Advanced Solid Tumors

Study Overview
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Brief Summary
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This trial is a multi-center, open-label, phase I, dose escalation study of PEP02 (liposomal encapsulated irinotecan) in combination with 5-FU and LV in patients with advanced solid tumors.

Detailed Description
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In this study, the initial starting dose of PEP02 is 60 mg/m2, and was escalated by increments of 20 mg/m2 between dose levels. 5-FU and LV was given as 24-hour infusion via an implanted central venous catheter, with dose fixed at 2000 mg/m2 and 200 mg/m2, respectively. PEP02 was administered on Day 1; 5-FU/LV was started after the end of PEP02 infusion on Day 1 and also on Day 8. Treatment repeated every 3 weeks and it was regarded as one cycle of treatment.

Official Title
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A Multi-Center, Open-Label Phase I Dose-Escalation Study of PEP02 in Combination With 5-fluorouracil (5-FU) and Leucovorin (LV) in Advanced Solid Tumors

Conditions
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Solid Tumor

Intervention / Treatment
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* Drug: PEP02
* Drug: 5-FU
* Drug: LV


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically or cytologically confirmed solid tumor which was locally advanced or metastatic and had failed to standard chemotherapy or no standard treatment was available ECOG performance status 0 or 1 With normal organ and marrow function Exclusion Criteria: Have had major surgery, chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or have not recovered from toxicities due to previous treatment With known or suspicious primary or secondary brain tumors History of allergic reactions attributed to compounds of similar chemical or biologic composition to PEP02, 5-FU or leucovorin HBsAg+ or anti-HCV+ patients with splenomegaly (defined as spleen size > 11 cm in CT scan) Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, and history of symptomatic congestive heart failure of Functional Class II or more (New York Heart Association) and ischemic heart diseases (i.e. myocardial infarction or angina pectoris), cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements Pregnant or breast feeding females (a pregnancy test must be performed on all females who are of child-bearing potential before entering the study and the result must be negative) Had received irinotecan treatment

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 70 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: PEP02 + 5-FU/LV<br>The initial starting dose of PEP02 is 60 mg/m2, and was escalated by increments of 20 mg/m2 between dose levels. 5-FU and LV were given as 24-hour infusion via an implanted central venous catheter, with dose fixed at 2000 mg/m2 and 200 mg/m2, respectively. PEP02 was administered on Day 1; 5-FU/LV was started after the end of PEP02 infusion on Day 1 and also on Day 8. | Drug: PEP02<br>* PEP02 was administered on Day 1. Treatment repeated every 3 weeks and it was regarded as one cycle of treatment.<br>* Other names: liposomal irinotecan;Drug: 5-FU<br>* 5-FU/LV were started after the end of PEP02 infusion on Day 1 and also on Day 8. Treatment repeated every 3 weeks and it was regarded as one cycle of treatment.<br>* Other names: Fluorouracil;Drug: LV<br>* 5-FU/LV were started after the end of PEP02 infusion on Day 1 and also on Day 8. Treatment repeated every 3 weeks and it was regarded as one cycle of treatment.<br>* Other names: Leucovorin;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Dose limiting toxicity (DLT) according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 4.0 |  | 3 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| objective tumor response according to Response Evaluation Criteria In Solid Tumours (RECIST) 1.0 |  | 6 weeks |