Phase I and Pharmacokinetic Study of Biweekly PEP02 in mCRC Refractory to 1st-line Oxaliplatin Base Therapy

Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to evaluate the dose-limiting toxicity (DLT), toxicity profile, maximum tolerated dose (MTD) and characterize the pharmacokinetics of biweekly PEP02 treatment.

Official Title
-----------------
Phase I and Pharmacokinetic Study of Biweekly PEP02 (Liposome Irinotecan) in Patients With Metastatic Colorectal Cancer Refractory to First-line Oxaliplatin-based Chemotherapy

Conditions
-----------------
Metastatic Colorectal Cancer

Intervention / Treatment
-----------------
* Drug: PEP02


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Histopathologically confirmed metastatic colorectal cancer Documented disease progression after first-line chemotherapy containing oxaliplatin Both genders, age 18 years ECOG performance status 0 or 1 Adequate organ and marrow function Written informed consent to participate in the study Exclusion Criteria: Have received irinotecan treatment With active CNS metastases (indicated by clinical symptoms, cerebral edema, steroid requirement, or progressive growth) With clinically significant gastrointestinal disorder (e.g. bleeding, inflammation, obstruction, including partial or complete obstruction secondary to peritoneal carcinomatosis, or diarrhea > grade 1) With uncontrolled intercurrent illness that could limit study compliance considered to be ineligible for the study by the investigators including, but NOT limited to, any of the following:ongoing or active infection requiring antibiotic treatment, symptomatic congestive heart failure, unstable angina pectoris, or cardiac arrhythmia psychiatric illness or social situation that would preclude study compliance With other primary malignancies, except those remain disease-free for 3 or more years after curative treatment. Prior chemotherapy within 3 weeks Major surgery or radiotherapy within 4 weeks Prior participation in any investigational drug study within 3 weeks History of allergic reaction to liposome product Pregnant or breastfeeding (a urine pregnancy test must be performed on all patients who are of childbearing potential before entering the study, and the result must be negative)

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: PEP02<br> | Drug: PEP02<br>* Dose escalation: 50-100 mg/m2 biweekly<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To evaluate the DLT and the toxicity profile |  | 3 years | 
| To establish the MTD |  | 3 years | 
| To characterize the pharmacokinetics of biweekly PEP02 in patients with metastatic colorectal cancer who failed to first-line oxaliplatin-based chemotherapy |  | 3 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To collect data for preliminary evaluation of tumor response |  | 3 years | 
| To explore the association of the pharmacogenetics of PEP02 including UGT1A family - UGT1A1 and UGT1A9 with pharmacokinetic parameters and toxicity |  | 3 years |