Oral Paclitaxel Efficacy Safety and PK in Recurrent and Metastatic Breast Cancer

Study Overview
=================
Brief Summary
-----------------
The objective of this study is to evaluate the efficacy, safety and pharmacokinetics of DHP107 (Oral Paclitaxel, Korea brand name: Liporaxel®) compared to IV Paclitaxel in patients with Recurrent or Metastatic Breast Cancer.

Official Title
-----------------
A Multi-center, Open-label, Phase 2 Clinical Trial to Evaluate the Efficacy, Safety and Pharmacokinetics of DHP107 (Liporaxel®, Oral Paclitaxel) Compared to IV Paclitaxel in Patients With Recurrent or Metastatic Breast Cancer(OPERA)

Conditions
-----------------
Recurrent or Metastatic Breast Cancer

Intervention / Treatment
-----------------
* Drug: DHP107
* Drug: IV Paclitaxel


Participation Criteria
=================
Eligibility Criteria
-----------------
Key Inclusion Criteria: Subjects with confirmed diagnosis of recurrent or metastatic breast cancer based on histopathology examination Subjects with diagnosis of HER2-negative breast cancer that was confirmed by IHC or in situ hybridization (ISH) assessment of tumor samples Subjects who have received up to 3 lines of therapy for advanced disease, without prior exposure to taxane in the advanced stage setting Subjects who have a performance status of ≤2 on the Eastern Cooperative Oncology Group (ECOG) scale. Subjects who have measurable disease according to the Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST version 1.1). Key Exclusion Criteria: Subjects who have received prior taxane therapy in the metastatic setting Subjects whose adjuvant or neoadjuvant treatment for early stage breast cancer was completed within 6 months prior to entry into the study. Subjects with neuropathy grade ≥2 based on CTCAE v4.03 at the time of study entry Subjects with symptomatic, untreated metastases to the central nervous system (CNS) at the time of screening. Subjects who have received any investigational drugs or devices within 4 weeks before the first day of study treatment (C1D1).

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
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Subjects will be assigned to DHP107 or IV paclitaxel in a ratio of 2:1 (n=48 to DHP107 and n=24 to IV paclitaxel)
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: DHP107<br>The 12 eligible subjects will receive DHP107 and be taken blood samples for PK analysis on Day 1, 8 of cycle 1. Total 48 subjects (including PK subjects) will receive DHP107 200 mg/m2 orally twice daily on Days 1, 8 and 15 every 28 days. | Drug: DHP107<br>* DHP107 200mg/m2 orally twice daily on Days 1, 8 and 15 every 28 days<br>* Other names: Liporaxel®, Oral Paclitaxel;|
| Experimental: IV paclitaxel<br>Total 24 subject will receive IV paclitaxel 80 mg/m2 weekly.(3 weeks on/1 week off) | Drug: IV Paclitaxel<br>* IV Paclitaxel 80 mg/m2 QW (3 weeks on/1 week off)<br>* Other names: Taxol Injection;|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective Response Rate(ORR) | ORR is defined by Response Evaluation Criteria in Solid Tumors (RECIST) (v.1.1) criteria | Every 8 weeks upto 18 months from randomization date | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression free survival(PFS) | PFS is defined as the time from date of randomization until the date of first documented progression or death. | Up to 18 months from randomization date | 
| Overall survival(OS) | OS is defined as the time from the date of inclusion to the date of death. | Up to 36 months from FPI | 
| Time to treatment failure(TTF) | TTF is defined as the time from the randomization date to the date of discontinuation of treatment, regardless of the cause. | Up to 18 months from randomization date | 
| Duration of response(DOR) | DOR is the time between the initial response to therapy and subsequent disease progression or relapse. | Up to 18 months from randomization date | 
| Disease control rate(DCR) | DCR is defined as the percentage of subjects who were evaluated for complete response(CR), partial response(PR), and stable disease(SD) as the best response among from randomization. | Up to 18 months from randomization date | 
| Quality of life(QoL) | Evaluate changes compared to baseline using European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) | after randomization(C1D1), D1 of every 3rd cycle(each cycle consists of 28 days) up to 18 months | 
| AUC | Area under the plasma concentration-time curve | on Day 1 of Cycle 1(each cycle consists of 28days) at predose, 1, 2, 3, 4, 6 and 10 hrs post dose (before the 2nd dose on Day 1) and on Day 8 of Cycle 1 at predose (before the 1st dose on Day 8) | 
| Cmax | Maximum concentration | on Day 1 of Cycle 1(each cycle consists of 28days) at predose, 1, 2, 3, 4, 6 and 10 hrs post dose (before the 2nd dose on Day 1) and on Day 8 of Cycle 1 at predose (before the 1st dose on Day 8) | 
| Tmax | Time to reach observed maximum concentration | on Day 1 of Cycle 1(each cycle consists of 28days) at predose, 1, 2, 3, 4, 6 and 10 hrs post dose (before the 2nd dose on Day 1) and on Day 8 of Cycle 1 at predose (before the 1st dose on Day 8) | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Breast Cancer, DHP107, Paclitaxel, Liporaxel