Gemcitabine/Taxotere/Xeloda (GTX) With Cisplatin in Subjects With Metastatic Pancreatic Cancer

Study Overview
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Brief Summary
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Primary Objectives To assess the efficacy of the combination of gemcitabine, taxotere, and xeloda (GTX) with cisplatin in subjects with metastatic pancreatic cancer based on the progression-free survival (PFS) rate at 6 month. Secondary Objectives To assess safety and characterize toxicities of the combination of GTX with cisplatin in subjects with metastatic pancreatic cancer. To estimate disease control rate (DCR), PFS, and overall survival (OS). To estimate a PFS rate of an expansion cohort testing an alternative schedule. Study Design This study is a single arm phase II study to assess the efficacy of GTX with cisplatin in subjects with metastatic pancreatic cancer. Approximately 38 evaluable subjects will be enrolled, 28 in the initial cohort and 10 in the expansion cohort The study will have a safety run-in phase consisting of 6 subjects. To ensure that the combination is safe, the first six subjects will be treated at DL1 and observed for limiting toxicity for the first 2 cycles before continuation with further accrual. After the safety run-in, the study will be continuously monitored for adverse events. The primary endpoint will be the PFS rate at 6 month, which is defined as the proportion of subjects alive, free of disease progression at 6 months. The treatment regimen would be considered of insufficient activity for further study in this population if PFS rate at 6 months is 50% or less, and the minimum required level of efficacy that would warrant further study with the proposed regimen is a 75% PFS rate at 6 months. The study design includes interim monitoring for futility using a predictive probability approach. We will stop the study early if given the information at the interim analysis, it is unlikely that the PFS rate at 6 months will be greater than 50% if the study continues to the end.

Official Title
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Phase II Study of Gemcitabine/Taxotere/Xeloda (GTX) in Combination With Cisplatin in Subjects With Metastatic Pancreatic Cancer

Conditions
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Pancreatic Cancer

Intervention / Treatment
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* Drug: Gemcitabine
* Drug: Taxotere
* Drug: Xeloda
* Drug: Cisplatin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects must have histologically or cytologically confirmed metastatic pancreatic adenocarcinoma. Subjects with islet cell neoplasms are excluded. Subjects with mixed histology will be excluded. Subject has one or more tumors measurable by CT scan using RECIST 1.1 criteria. MRI is acceptable if a CT scan is contraindicated. Patient must be chemotherapy naïve or must have completed chemotherapy greater than 5 years prior to enrollment. Male or non-pregnant and non-lactating female of age >18 years ECOG performance status <1. ECOG 0 indicates that the patient is fully active and able to carry on all pre-disease activities without restriction; and, ECOG 1 indicates that the patient is restricted in physically strenuous activity but is ambulatory and able to carry out work of a light or sedentary nature Life expectancy of greater than 12 weeks. Subjects must have adequate organ and marrow function as defined below: WBC ≥ 3,500/mcL Absolute Neutrophil Count ≥1,500/mcL Platelets ≥100 x 10^9/L Hemoglobin ≥ 9 g/d Total Bilirubin within normal institutional limits Alkaline phosphatase ≤ 2.5 x ULN (≤ 5 X ULN for subjects with documented liver metastases) AST(SGOT)/ALT(SGPT) ≤ 2.5 x ULN (≤ 5 X ULN for subjects with documented liver metastases) Creatinine within normal institutional limits OR Creatinine clearance ≥ 60 mL/min/1.73 m2 for subjects with creatinine levels above institutional normal. Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. Willingness to undergo a tumor biopsy (implemented after the first 6 patients). Ability to understand and the willingness to sign a written informed consent document. Exclusion Criteria: Subjects who have had any prior chemotherapy within 5 years of enrollment Subjects who have had radiotherapy for pancreatic cancer. Age ≥ 76 years Subjects who are receiving or have received any other investigational agents within 28 days prior to Day 1 of treatment in this study. Subject has undergone major surgery, other than diagnostic surgery (i.e.--surgery done to obtain a biopsy for diagnosis or an aborted Whipple), within 28 days prior to Day 1 of treatment in this study. Subject has known brain metastases unless previously treated and well controlled for at least 3 months (defined as stable clinically, no edema, no steroids). History of hypersensitivity or allergic reactions attributed to compounds of similar chemical or biologic composition to gemcitabine, taxotere, xeloda, or cisplatin. Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements. Subject has serious medical risk factors involving any of the major organ systems such that the Investigator considers it unsafe for the subject to receive an experimental research drug. Subject has active, uncontrolled bacterial, viral, or fungal infection(s) requiring systemic therapy. Subject has a known history of infection with HIV, hepatitis B, or hepatitis C. Subject is pregnant or breast feeding. Subject is unwilling or unable to comply with study procedures. Subject with an unhealed surgical wound or other clinically significant wound.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 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: GTX-C<br>Each cycle is 21 days (2 weeks Tx + 1 week off). Xeloda given days 1-14, Gemcitabine, Taxotere, and Cisplatin given days 4 and 11. For expansion cohort, each cycle is 28 days (2 weeks of Tx + 2 weeks off) | Drug: Gemcitabine<br>* IV on Days 4 and 11<br>Drug: Taxotere<br>* IV on Days 4 and 11<br>* Other names: Docetaxel;Drug: Xeloda<br>* orally, twice a day Days 1-14<br>* Other names: Capecitabine;Drug: Cisplatin<br>* IV Days 4 and 11<br>* Other names: CDDP;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Without Disease Progression (Progression-Free Survival) at 6 Months | PFS is defined as the percentage of patients with disease progression (progressive disease [PD] or relapse from complete response [CR] as assessed using RECIST 1.1 criteria) or death due to any cause at 6 months. Per RECIST 1.1 criteria, CR = disappearance of all target lesions, Partial Response (PR) is =>30% decrease in sum of diameters of target lesions, Progressive Disease (PD) is >20% increase in sum of diameters of target lesions, Stable Disease (SD) is <30% decrease or <20% increase in sum of diameters of target lesions. Estimation based on the Kaplan-Meier curve. | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Patients Experiencing a Grade 3 or Above Treatment-related Toxicity | When calculating the incidence of AEs, each AE (as defined by NCI CTCAE v4.03) will be counted only once for a given subject. AEs collected from time of first dose of study drug through 28 days after the last dose of study drug. The median duration of treatment was up to 23 months. | Up to 23 months | 
| Disease Control Rate (DCR) | DCR is defined as the percentage of patients achieving a complete response (CR), partial response (PR), or stable disease (SD) based on the Response Evaluation Criteria in Solid Tumors (RECIST 1.1). CR = disappearance of all target lesions, PR is =>30% decrease in sum of diameters of target lesions, progressive disease (PD) is >20% increase in sum of diameters of target lesions, stable disease (SD) is <30% decrease or <20% increase in sum of diameters of target lesions. | Up to 22 months | 
| Progression-free Survival (PFS) | PFS is defined as the the number of months from the date of first dose to disease progression (progressive disease [PD] or relapse from complete response [CR] as assessed using RECIST 1.1 criteria) or death due to any cause . Per RECIST 1.1 criteria, CR = disappearance of all target lesions, Partial Response (PR) is =>30% decrease in sum of diameters of target lesions, Progressive Disease (PD) is >20% increase in sum of diameters of target lesions, Stable Disease (SD) is <30% decrease or <20% increase in sum of diameters of target lesions. Estimation based on the Kaplan-Meier curve. | Up to 21 months | 
| Overall Survival (OS) | OS (in months) will be measured from date of first dose until death (OS will be censored on the date the subject was last known to be alive for subjects without documentation of death at the time of analysis). Estimation based on the Kaplan-Meier curve. | Up to 28 months |