Study of Gemcitabine/Taxotere/Xeloda (GTX) in Combination With Cisplatin and Irinotecan in Subjects With Metastatic Pancreatic Cancer

Study Overview
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Brief Summary
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This study will be looking at whether gemcitabine, taxotere, and xeloda (GTX) in combination with cisplatin and irinotecan is effective (anti-tumor activity) and safe in patients with metastatic pancreatic cancer.

Detailed Description
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The study is being done in 2 parts. The first part is the dose escalation (Phase I) part of the study where the dose of irinotecan is increased until the highest safe dose of irinotecan is defined that can be given with gemcitabine, taxotere, xeloda, and cisplatin. After the safe dose of irinotecan in combination with gemcitabine, taxotere, xeloda, and cisplatin is defined, the second part of the study (Phase 2) will use these defined doses to look at how effective these drugs are against advanced pancreatic cancer.

Official Title
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Phase 1/2 Study of Gemcitabine/Taxotere/Xeloda (GTX) in Combination With Cisplatin and Irinotecan in Subjects With Metastatic Pancreatic Cancer

Conditions
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Metastatic Pancreatic Adenocarcinoma

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


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically or cytologically confirmed untreated metastatic pancreatic adenocarcinoma. Have measurable disease. Male or non-pregnant and non-lactating female of age >18 years. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 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 Subjects must have adequate organ and marrow function. Must use acceptable form of birth control prior to study and and for the duration of study. Willing and able to comply with study procedures Exclusion Criteria: Patient who have had any prior chemotherapy within 5 years of enrollment. Patient who have had radiotherapy for pancreatic cancer. Age ≥ 76 years Patient who is receiving or have received any other investigational agents within 28 days prior to Day 1 of treatment in this study. Patient who has undergone major surgery, other than diagnostic surgery within 28 days prior to Day 1 of treatment in this study. Patient who has known brain metastases. Patient with history of hypersensitivity or allergic reactions attributed to compounds of similar chemical or biologic composition to gemcitabine, taxotere, xeloda, cisplatin, or irinotecan. Patient with uncontrolled intercurrent illness including, but not limited to, uncontrolled infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements Patient who has serious medical risk factors involving any of the major organ systems. Patient who has known history of infection with HIV, hepatitis B, or hepatitis C. Pregnant or breast feeding. Patient is unwilling or unable to comply with study procedures Patient with clinically significant wound

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 76 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: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Dose level 1 - Phase 1<br>Gemcitabine - 400 mg/m^2 Taxotere - 20 mg/m^2 Xeloda - 500 mg/twice daily (BID) Cisplatin - 15 mg/m^2 Irinotecan - 20 mg/m^2 | Drug: Gemcitabine<br>* IV on days 4 and 11 of a 21 day cycle<br>* Other names: Gemzar;Drug: Taxotere<br>* IV on days 4 and 11 of a 21 day cycle<br>* Other names: Docetaxel;Drug: Xeloda<br>* Twice a day orally on days 1 through 14 of a 21 day cycle<br>* Other names: Capecitabine;Drug: Cisplatin<br>* IV on days 4 and 11 of a 21 day cycle<br>* Other names: Platinol;Drug: Irinotecan<br>* IV on days 4 and 11 of a 21 day cycle<br>* Other names: Camptosar;|
| Experimental: Dose Level 2 - Phase 1<br>Gemcitabine - 400 mg/m^2 Taxotere - 20 mg/m^2 Xeloda - 500 mg/BID Cisplatin - 15 mg/m^2 Irinotecan - 40 mg/m^2 | Drug: Gemcitabine<br>* IV on days 4 and 11 of a 21 day cycle<br>* Other names: Gemzar;Drug: Taxotere<br>* IV on days 4 and 11 of a 21 day cycle<br>* Other names: Docetaxel;Drug: Xeloda<br>* Twice a day orally on days 1 through 14 of a 21 day cycle<br>* Other names: Capecitabine;Drug: Cisplatin<br>* IV on days 4 and 11 of a 21 day cycle<br>* Other names: Platinol;Drug: Irinotecan<br>* IV on days 4 and 11 of a 21 day cycle<br>* Other names: Camptosar;|
| Experimental: Dose Level 3 - Phase 1<br>Gemcitabine - 400 mg/m^2 Taxotere - 20 mg/m^2 Xeloda - 500 mg/BID Cisplatin - 15 mg/m^2 Irinotecan - 60 mg/m^2 | Drug: Gemcitabine<br>* IV on days 4 and 11 of a 21 day cycle<br>* Other names: Gemzar;Drug: Taxotere<br>* IV on days 4 and 11 of a 21 day cycle<br>* Other names: Docetaxel;Drug: Xeloda<br>* Twice a day orally on days 1 through 14 of a 21 day cycle<br>* Other names: Capecitabine;Drug: Cisplatin<br>* IV on days 4 and 11 of a 21 day cycle<br>* Other names: Platinol;Drug: Irinotecan<br>* IV on days 4 and 11 of a 21 day cycle<br>* Other names: Camptosar;|
| Experimental: Dose Level 1a - Phase 1<br>Gemcitabine - 500 mg/m^2 Taxotere - 20 mg/m^2 Xeloda - 500 mg/BID Cisplatin - 20 mg/m^2 Irinotecan - 20 mg/m^2 | Drug: Gemcitabine<br>* IV on days 4 and 11 of a 21 day cycle<br>* Other names: Gemzar;Drug: Taxotere<br>* IV on days 4 and 11 of a 21 day cycle<br>* Other names: Docetaxel;Drug: Xeloda<br>* Twice a day orally on days 1 through 14 of a 21 day cycle<br>* Other names: Capecitabine;Drug: Cisplatin<br>* IV on days 4 and 11 of a 21 day cycle<br>* Other names: Platinol;Drug: Irinotecan<br>* IV on days 4 and 11 of a 21 day cycle<br>* Other names: Camptosar;|
| Experimental: Dose level 1b - Phase 1<br>Gemcitabine - 500 mg/m^2 Taxotere - 20 mg/m^2 Xeloda - 500 mg/BID Cisplatin - 20 mg/m^2 Irinotecan - 40 mg/m^2 | Drug: Gemcitabine<br>* IV on days 4 and 11 of a 21 day cycle<br>* Other names: Gemzar;Drug: Taxotere<br>* IV on days 4 and 11 of a 21 day cycle<br>* Other names: Docetaxel;Drug: Xeloda<br>* Twice a day orally on days 1 through 14 of a 21 day cycle<br>* Other names: Capecitabine;Drug: Cisplatin<br>* IV on days 4 and 11 of a 21 day cycle<br>* Other names: Platinol;Drug: Irinotecan<br>* IV on days 4 and 11 of a 21 day cycle<br>* Other names: Camptosar;|
| Experimental: Phase 2<br>Gemcitabine - 500 mg/m^2 Taxotere - 20 mg/m^2 Xeloda - 500 mg/BID Cisplatin - 20 mg/m^2 Irinotecan - 20 mg/m^2 | Drug: Gemcitabine<br>* IV on days 4 and 11 of a 21 day cycle<br>* Other names: Gemzar;Drug: Taxotere<br>* IV on days 4 and 11 of a 21 day cycle<br>* Other names: Docetaxel;Drug: Xeloda<br>* Twice a day orally on days 1 through 14 of a 21 day cycle<br>* Other names: Capecitabine;Drug: Cisplatin<br>* IV on days 4 and 11 of a 21 day cycle<br>* Other names: Platinol;Drug: Irinotecan<br>* IV on days 4 and 11 of a 21 day cycle<br>* Other names: Camptosar;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum Tolerated Dose (MTD) of Gemcitabine | Dose escalation (phase I portion of the trial only) to determine the MTD in mg/m^2. | 28 days | 
| Maximum Tolerated Dose (MTD) of Docetaxel | Dose escalation (phase I portion of the trial only) to determine the MTD in mg/m^2. | 28 days | 
| Maximum Tolerated Dose (MTD) of Capecitabine | Dose escalation (phase I portion of the trial only) to determine the MTD in mg for twice daily (BID) use. | 28 days | 
| Maximum Tolerated Dose (MTD) of Cisplatin | Dose escalation (phase I portion of the trial only) to determine the MTD in mg/m^2. | 28 days | 
| Maximum Tolerated Dose (MTD) of Irinotecan | Dose escalation (phase I portion of the trial only) to determine the MTD in mg/m^2. | 28 days | 
| Overall Survival (OS) Rate at 9 Months | OS will be measured as the percentage of subjects alive at 9 months. (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. (Phase 2 data only) | 9 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Response Rate (RR) Using RECIST 1.1 Criteria | RR is defined as the percentage of participants achieving a complete response (CR) or partial response (PR) based on the Response Evaluation Criteria in Solid Tumors (RECIST 1.1) at any time during the study. 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. | 43 months | 
| Disease Control Rate (DCR) Using RECIST 1.1 Criteria | DCR is defined as the percentage of participants achieving a complete response (CR) or partial response (PR) and stable disease (SD) based on the Response Evaluation Criteria in Solid Tumors (RECIST 1.1) at any time during the study. 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. | 43 months | 
| Progression-free Survival (PFS) Using RECIST 1.1 Criteria | PFS is defined as 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. | 5 years | 
| Overall Survival (OS) | OS will be measured (in months) from date of first dose until death or end of follow-up (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. | 5 years |