Z-360 Plus GEM in Subjects With Metastatic Pancreatic Adenocarcinoma

Study Overview
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Brief Summary
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The primary objective of this study is to compare the efficacy of GEM plus Z-360 versus GEM plus placebo on the overall survival (OS) in subjects with metastatic Pancreatic Adenocarcinoma.

Official Title
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Randomized Phase II Study of Gemcitabine Plus Z-360 in Metastatic Pancreatic Adenocarcinoma Compared With Gemcitabine Plus Placebo ( ZIPANG Study )

Conditions
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Metastatic Pancreatic Adenocarcinoma

Intervention / Treatment
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* Drug: Z-360
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 1. Subjects with histological or cytological evidence of metastatic Pancreatic Adenocarcinoma, Measurable disease or non-measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST) version criteria 2. Subjects with a life expectancy of at least 12 weeks, 3. Subjects with an Eastern cooperative oncology group performance status (ECOG PS) of 0, 1 or 2, 4. Subjects with the following adequate organ functions: White blood cell count ≥3,000/μL (or absolute neutrophil count ≥1,500/μL) and ≤ 12,000/μL , Platelet count ≥100.0 × 10^9/L, Hemoglobin ≥9.0 g/dL, Serum creatinine ≤1.5 × the upper limit normal (ULN), Total bilirubin ≤2.0 × ULN, Serum aspartate transaminase levels ≤3.0 × ULN (≤5.0 × ULN in presence of liver metastases), and Serum alanine aminotransferase levels ≤3.0 × ULN (≤5.0 × ULN in presence of liver metastases). Exclusion Criteria: Subjects received the following previous therapies for Pancreatic Adenocarcinoma: Surgery within the 4 weeks prior to randomization, Radiation and chemoradiation within the 12 weeks prior to randomization, Radiation for pain relief within the 4 weeks prior to randomization, Gemcitabine used as a neoadjuvant or an adjuvant on surgery within the 24 weeks prior to randomization, Chemotherapy except GEM used as an adjuvant on surgery within the 4 weeks prior to randomization, Gemcitabine ≥600 mg/m^2 as sensitizer for chemoradiation, Gemcitabine <600 mg/m^2 as sensitizer for chemoradiation within the 12 weeks prior to randomization, Gemcitabine used for systemic chemotherapy, or Systemic chemotherapies except GEM within the 4 weeks prior to randomization.

Ages Eligible for Study
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Minimum Age: 20 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: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Z-360 60mg+Gemcitabine<br>Z-360 60 mg will be taken orally, twice daily (BID) after a meal. | Drug: Z-360<br>* Gemcitabine (1,000 mg/m^2) will be given by 30-minute intravenous infusion on Day 1, 8, and 15 followed by a one week rest in all 28-day Cycles, while Z-360 (60, 120 or 240 mg) will be taken orally, twice daily (BID) after a meal. Dosing will continue until the patient fulfills the withdrawal criteria.<br>|
| Experimental: Z-360 120mg+Gemcitabine<br>Z-360 120 mg will be taken orally, twice daily (BID) after a meal. | Drug: Z-360<br>* Gemcitabine (1,000 mg/m^2) will be given by 30-minute intravenous infusion on Day 1, 8, and 15 followed by a one week rest in all 28-day Cycles, while Z-360 (60, 120 or 240 mg) will be taken orally, twice daily (BID) after a meal. Dosing will continue until the patient fulfills the withdrawal criteria.<br>|
| Experimental: Z-360 240mg+Gemcitabine<br>Z-360 240 mg will be taken orally, twice daily (BID) after a meal. | Drug: Z-360<br>* Gemcitabine (1,000 mg/m^2) will be given by 30-minute intravenous infusion on Day 1, 8, and 15 followed by a one week rest in all 28-day Cycles, while Z-360 (60, 120 or 240 mg) will be taken orally, twice daily (BID) after a meal. Dosing will continue until the patient fulfills the withdrawal criteria.<br>|
| Placebo Comparator: Placebo+Gemcitabine<br>Placebo will be taken orally, twice daily (BID) after a meal. | Drug: Placebo<br>* Gemcitabine (1,000 mg/m^2) will be given by 30-minute intravenous infusion on Day 1, 8, and 15 followed by a one week rest in all 28-day Cycles, while placebo will be taken orally, twice daily (BID) after a meal. Dosing will continue until the patient fulfills the withdrawal criteria.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival |  | Approximately 24 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression Free Survival (PFS) |  | Approximately 24 months | 
| Time to Treatment Failure |  | Approximately 24 months | 
| Quality of Life |  | Approximately 24 months | 
| Safety parameters | Incidence of SAEs and AEs, laboratory test results, vital signs, ECG results and physical examination findings | Approximately 24 months | 
| Pharmacokinetics | To characterize the plasma pK of Z-360 when given in combination with GEM | Day1 | 
| Response Rate |  | Approximately 24 months | 
| Benefit Rate |  | Approximately 24 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Z-360, Pancreatic cancer, Pancreatic Adenocarcinoma