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

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

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.

Study Overview

• Status: Completed
• Conditions: Metastatic Pancreatic Adenocarcinoma
• Intervention / Treatment: Drug: Gemcitabine; Drug: Taxotere; Drug: Xeloda; Drug: Cisplatin; Drug: Irinotecan

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 47
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • Maryland
    • Baltimore, Maryland, United States, 21231
      • Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 76 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Histologically or cytologically confirmed untreated metastatic pancreatic adenocarcinoma.
2. Have measurable disease.
3. Male or non-pregnant and non-lactating female of age >18 years.
4. 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
5. Subjects must have adequate organ and marrow function.
6. Must use acceptable form of birth control prior to study and and for the duration of study.
7. Willing and able to comply with study procedures

Exclusion Criteria:

1. Patient who have had any prior chemotherapy within 5 years of enrollment.
2. Patient who have had radiotherapy for pancreatic cancer.
3. Age ≥ 76 years
4. Patient who is receiving or have received any other investigational agents within 28 days prior to Day 1 of treatment in this study.
5. Patient who has undergone major surgery, other than diagnostic surgery within 28 days prior to Day 1 of treatment in this study.
6. Patient who has known brain metastases.
7. Patient with history of hypersensitivity or allergic reactions attributed to compounds of similar chemical or biologic composition to gemcitabine, taxotere, xeloda, cisplatin, or irinotecan.
8. 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
9. Patient who has serious medical risk factors involving any of the major organ systems.
10. Patient who has known history of infection with HIV, hepatitis B, or hepatitis C.
11. Pregnant or breast feeding.
12. Patient is unwilling or unable to comply with study procedures
13. Patient with clinically significant wound

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Dose level 1 - Phase 1; 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; IV on days 4 and 11 of a 21 day cycle; Other Names: Gemzar; Drug: Taxotere; IV on days 4 and 11 of a 21 day cycle; Other Names: Docetaxel; Drug: Xeloda; Twice a day orally on days 1 through 14 of a 21 day cycle; Other Names: Capecitabine; Drug: Cisplatin; IV on days 4 and 11 of a 21 day cycle; Other Names: Platinol; Drug: Irinotecan; IV on days 4 and 11 of a 21 day cycle; Other Names: Camptosar
Experimental: Dose Level 2 - Phase 1; 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; IV on days 4 and 11 of a 21 day cycle; Other Names: Gemzar; Drug: Taxotere; IV on days 4 and 11 of a 21 day cycle; Other Names: Docetaxel; Drug: Xeloda; Twice a day orally on days 1 through 14 of a 21 day cycle; Other Names: Capecitabine; Drug: Cisplatin; IV on days 4 and 11 of a 21 day cycle; Other Names: Platinol; Drug: Irinotecan; IV on days 4 and 11 of a 21 day cycle; Other Names: Camptosar
Experimental: Dose Level 3 - Phase 1; 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; IV on days 4 and 11 of a 21 day cycle; Other Names: Gemzar; Drug: Taxotere; IV on days 4 and 11 of a 21 day cycle; Other Names: Docetaxel; Drug: Xeloda; Twice a day orally on days 1 through 14 of a 21 day cycle; Other Names: Capecitabine; Drug: Cisplatin; IV on days 4 and 11 of a 21 day cycle; Other Names: Platinol; Drug: Irinotecan; IV on days 4 and 11 of a 21 day cycle; Other Names: Camptosar
Experimental: Dose Level 1a - Phase 1; 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; IV on days 4 and 11 of a 21 day cycle; Other Names: Gemzar; Drug: Taxotere; IV on days 4 and 11 of a 21 day cycle; Other Names: Docetaxel; Drug: Xeloda; Twice a day orally on days 1 through 14 of a 21 day cycle; Other Names: Capecitabine; Drug: Cisplatin; IV on days 4 and 11 of a 21 day cycle; Other Names: Platinol; Drug: Irinotecan; IV on days 4 and 11 of a 21 day cycle; Other Names: Camptosar
Experimental: Dose level 1b - Phase 1; 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; IV on days 4 and 11 of a 21 day cycle; Other Names: Gemzar; Drug: Taxotere; IV on days 4 and 11 of a 21 day cycle; Other Names: Docetaxel; Drug: Xeloda; Twice a day orally on days 1 through 14 of a 21 day cycle; Other Names: Capecitabine; Drug: Cisplatin; IV on days 4 and 11 of a 21 day cycle; Other Names: Platinol; Drug: Irinotecan; IV on days 4 and 11 of a 21 day cycle; Other Names: Camptosar
Experimental: Phase 2; 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; IV on days 4 and 11 of a 21 day cycle; Other Names: Gemzar; Drug: Taxotere; IV on days 4 and 11 of a 21 day cycle; Other Names: Docetaxel; Drug: Xeloda; Twice a day orally on days 1 through 14 of a 21 day cycle; Other Names: Capecitabine; Drug: Cisplatin; IV on days 4 and 11 of a 21 day cycle; Other Names: Platinol; Drug: Irinotecan; IV on days 4 and 11 of a 21 day cycle; Other Names: Camptosar

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
• Collaborators: Swim Across America Laboratory
• Investigators: Principal Investigator: Dung Le, MD, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Study record dates

Study Major Dates

• Study Start (Actual): February 1, 2015
• Primary Completion (Actual): June 1, 2019
• Study Completion (Actual): February 1, 2020

Study Registration Dates

• First Submitted: December 19, 2014
• First Submitted That Met QC Criteria: December 19, 2014
• First Posted (Estimated): December 24, 2014

Study Record Updates

• Last Update Posted (Actual): July 21, 2023
• Last Update Submitted That Met QC Criteria: July 17, 2023
• Last Verified: July 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Topoisomerase Inhibitors; Topoisomerase I Inhibitors; Docetaxel; Capecitabine; Irinotecan; Gemcitabine
• Other Study ID Numbers: J14161 (Other Identifier: Swim Across America Laboratory); IRB00053208 (Other Identifier: JHMIRB)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO