A Study of Gemcitabine, Nab-paclitaxel, Capecitabine, Cisplatin, and Irinotecan in Metastatic Pancreatic Cancer
A Phase I/II Study of Gemcitabine, Nab-paclitaxel, Capecitabine, Cisplatin, and Irinotecan (GAX-CI) in Combination in Metastatic Pancreatic Cancer
Study Overview
Status
Conditions
Detailed Description
This was a two-part, single-institution, open-label, dose-escalation, phase 1/2 study to evaluate the clinical activity of gemcitabine, nab-paclitaxel, capecitabine, cisplatin, and irinotecan in patients with metastatic pancreatic cancer.
Part 1 of the study was a Phase 1 3 + 3 dose escalation study designed to evaluate the maximally tolerated dose (MTD) and safety of increasing doses of nab-paclitaxel in combination with gemcitabine, capecitabine, cisplatin, and irinotecan. There were two cohorts of dose escalations. The two cohorts differed based on the treatment cycle length (28 days for Cohort 1 and 21 days for Cohort 2). Dose escalation started with Cohort 1. Enrollment for Cohort 2 dose level 1 began once dose level 2 of Cohort 1 was shown to be safe and did not exceed MTD.
Part 2 was a Phase 2 expansion cohort study for the evaluation of efficacy once the MTD had been determined.
Study Type
Enrollment (Actual)
Phase
- Phase 2
- Phase 1
Contacts and Locations
Study Locations
-
-
Maryland
-
Baltimore, Maryland, United States, 21231
- Sidney Kimmel Comprehensive Cancer Center
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
Inclusion Criteria:
- Have histologically or cytologically confirmed untreated metastatic pancreatic adenocarcinoma.
- Patients with the presence of at least one measurable lesion.
- Male or non-pregnant and non-lactating female of age >18 years.
- Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1.
- Patients must have adequate organ and marrow function defined by study-specified laboratory tests.
- Must use acceptable form of birth control while on study.
- Ability to understand and willingness to sign a written informed consent document.
Exclusion Criteria:
- Patients who will be considered for surgery are ineligible.
- 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, nab-paclitaxel, capecitabine, 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.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Non-Randomized
- Interventional Model: Sequential Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
|---|---|
|
Experimental: Phase 1, Cohort 1, Dose level 1
Gemcitabine: 500 mg/m^2, IV over 30 minutes; Days 1 and 15 of a 28 day cycle Nab-paclitaxel: 40 mg/m^2, IV over 30 minutes; Days 1 and 15 of a 28 day cycle Capecitabine: 500 mg BID, PO twice daily (BID); Days 1-7, 15-21 of a 28 day cycle Cisplatin: 20 mg/m^2, IV over 60 minutes; Days 1 and 15 of a 28 day cycle Irinotecan: 20 mg/m^2, IV over 30 minutes; Days 1 and 15 of a 28 day cycle |
IV over 30 minutes; Days 1 and 15
Other Names:
IV over 30 minutes; Days 1 and 15
Other Names:
PO twice daily (BID); Days 1-7, 15-21
Other Names:
IV over 60 minutes; Days 1 and 15
Other Names:
IV over 30 minutes; Days 1 and 15
Other Names:
IV over 30 minutes; Days 4 and 11
Other Names:
IV over 30 minutes; Days 4 and 11
Other Names:
PO BID; Days 1- 14
Other Names:
IV over 60 minutes; Days 4 and 11
Other Names:
IV over 30 minutes; Days 4 and 11
Other Names:
|
|
Experimental: Phase 1, Cohort 1, Dose level 2
Gemcitabine 500 mg/m^2, IV over 30 minutes; Days 1 and 15 of a 28 day cycle Nab-paclitaxel 60 mg/m^2, IV over 30 minutes; Days 1 and 15 of a 28 day cycle Capecitabine: 500 mg BID: PO twice daily (BID); Days 1-7, 15-21 of a 28 day cycle Cisplatin: 20 mg/m^2, IV over 60 minutes; Days 1 and 15 of a 28 day cycle Irinotecan: 20 mg/m^2, IV over 30 minutes; Days 1 and 15 of a 28 day cycle |
IV over 30 minutes; Days 1 and 15
Other Names:
IV over 30 minutes; Days 1 and 15
Other Names:
PO twice daily (BID); Days 1-7, 15-21
Other Names:
IV over 60 minutes; Days 1 and 15
Other Names:
IV over 30 minutes; Days 1 and 15
Other Names:
IV over 30 minutes; Days 4 and 11
Other Names:
IV over 30 minutes; Days 4 and 11
Other Names:
PO BID; Days 1- 14
Other Names:
IV over 60 minutes; Days 4 and 11
Other Names:
IV over 30 minutes; Days 4 and 11
Other Names:
|
|
Experimental: Phase 1, Cohort 1, Dose level 3
Gemcitabine: 500 mg/m^2, IV over 30 minutes; Days 1 and 15 of a 28 day cycle Nab-paclitaxel: 80 mg/m^2, IV over 30 minutes; Days 1 and 15 of a 28 day cycle Capecitabine: 500 mg BID, PO twice daily (BID); Days 1-7, 15-21 of a 28 day cycle Cisplatin 20 mg/m^2, IV over 60 minutes; Days 1 and 15 of a 28 day cycle Irinotecan:20 mg/m^2, IV over 30 minutes; Days 1 and 15 of a 28 day cycle |
IV over 30 minutes; Days 1 and 15
Other Names:
IV over 30 minutes; Days 1 and 15
Other Names:
PO twice daily (BID); Days 1-7, 15-21
Other Names:
IV over 60 minutes; Days 1 and 15
Other Names:
IV over 30 minutes; Days 1 and 15
Other Names:
IV over 30 minutes; Days 4 and 11
Other Names:
IV over 30 minutes; Days 4 and 11
Other Names:
PO BID; Days 1- 14
Other Names:
IV over 60 minutes; Days 4 and 11
Other Names:
IV over 30 minutes; Days 4 and 11
Other Names:
|
|
Experimental: Phase 1, Cohort 1, Dose level 4
Gemcitabine:500 mg/m^2, IV over 30 minutes; Days 1 and 15 of a 28 day cycle Nab-paclitaxel:100 mg/m^2, IV over 30 minutes; Days 1 and 15 of a 28 day cycle Capecitabine:500 PO twice daily (BID); Days 1-7, 15-21 of a 28 day cycle Cisplatin:20 mg/m^2, IV over 60 minutes; Days 1 and 15 of a 28 day cycle Irinotecan:20 mg/m^2, IV over 30 minutes; Days 1 and 15 of a 28 day cycle |
IV over 30 minutes; Days 1 and 15
Other Names:
IV over 30 minutes; Days 1 and 15
Other Names:
PO twice daily (BID); Days 1-7, 15-21
Other Names:
IV over 60 minutes; Days 1 and 15
Other Names:
IV over 30 minutes; Days 1 and 15
Other Names:
IV over 30 minutes; Days 4 and 11
Other Names:
IV over 30 minutes; Days 4 and 11
Other Names:
PO BID; Days 1- 14
Other Names:
IV over 60 minutes; Days 4 and 11
Other Names:
IV over 30 minutes; Days 4 and 11
Other Names:
|
|
Experimental: Phase 1, Cohort 1, Dose level 5
Gemcitabine:500 mg/m^2, IV over 30 minutes; Days 1 and 15 of a 28 day cycle Nab-paclitaxel:125 mg/m^2, IV over 30 minutes; Days 1 and 15 of a 28 day cycle Capecitabine: 500 mg BID, PO twice daily (BID); Days 1-7, 15-21 of a 28 day cycle Cisplatin:20 mg/m^2, IV over 60 minutes; Days 1 and 15 of a 28 day cycle Irinotecan: 20 mg/m^2, IV over 30 minutes; Days 1 and 15 of a 28 day cycle |
IV over 30 minutes; Days 1 and 15
Other Names:
IV over 30 minutes; Days 1 and 15
Other Names:
PO twice daily (BID); Days 1-7, 15-21
Other Names:
IV over 60 minutes; Days 1 and 15
Other Names:
IV over 30 minutes; Days 1 and 15
Other Names:
IV over 30 minutes; Days 4 and 11
Other Names:
IV over 30 minutes; Days 4 and 11
Other Names:
PO BID; Days 1- 14
Other Names:
IV over 60 minutes; Days 4 and 11
Other Names:
IV over 30 minutes; Days 4 and 11
Other Names:
|
|
Experimental: Phase 1, Cohort 2, Dose level 1
Gemcitabine: 500 mg/m^2, IV over 30 minutes; Days 4 and 11 of a 21 day cycle Nab-paclitaxel:40 mg/m^2, IV over 30 minutes; Days 4 and 11 of a 21 day cycle Capecitabine:500 mg BID, PO twice daily (BID); Days 1-14 of a 21 day cycle Cisplatin:20 mg/m^2, IV over 60 minutes; Days 4 and 11 of a 21 day cycle Irinotecan: 20 mg/m^2, IV over 30 minutes; Days 4 and 11 of a 21 day cycle |
IV over 30 minutes; Days 1 and 15
Other Names:
IV over 30 minutes; Days 1 and 15
Other Names:
PO twice daily (BID); Days 1-7, 15-21
Other Names:
IV over 60 minutes; Days 1 and 15
Other Names:
IV over 30 minutes; Days 1 and 15
Other Names:
IV over 30 minutes; Days 4 and 11
Other Names:
IV over 30 minutes; Days 4 and 11
Other Names:
PO BID; Days 1- 14
Other Names:
IV over 60 minutes; Days 4 and 11
Other Names:
IV over 30 minutes; Days 4 and 11
Other Names:
|
|
Experimental: Phase 1, Cohort 2, Dose level 2
Gemcitabine: 500 mg/m^2, IV over 30 minutes; Days 4 and 11 of a 21 day cycle Nab-paclitaxel:60 mg/m^2, IV over 30 minutes; Days 4 and 11 of a 21 day cycle Capecitabine:500mg BID, PO twice daily (BID); Days 1-14 of a 21 day cycle Cisplatin:20 mg/m^2, IV over 60 minutes; Days 4 and 11 of a 21 day cycle Irinotecan: 20 mg/m^2, IV over 30 minutes; Days 4 and 11 of a 21 day cycle |
IV over 30 minutes; Days 1 and 15
Other Names:
IV over 30 minutes; Days 1 and 15
Other Names:
PO twice daily (BID); Days 1-7, 15-21
Other Names:
IV over 60 minutes; Days 1 and 15
Other Names:
IV over 30 minutes; Days 1 and 15
Other Names:
IV over 30 minutes; Days 4 and 11
Other Names:
IV over 30 minutes; Days 4 and 11
Other Names:
PO BID; Days 1- 14
Other Names:
IV over 60 minutes; Days 4 and 11
Other Names:
IV over 30 minutes; Days 4 and 11
Other Names:
|
|
Experimental: Phase 1, Cohort 2, Dose level 3
Gemcitabine: 500 mg/m^2, IV over 30 minutes; Days 4 and 11 of a 21 day cycle Nab-paclitaxel:80 mg/m^2, IV over 30 minutes; Days 4 and 11 of a 21 day cycle Capecitabine:500mg BID, PO twice daily (BID); Days 1-14 of a 21 day cycle Cisplatin:20 mg/m^2, IV over 60 minutes; Days 4 and 11 of a 21 day cycle Irinotecan: 20 mg/m^2, IV over 30 minutes; Days 4 and 11 of a 21 day cycle |
IV over 30 minutes; Days 1 and 15
Other Names:
IV over 30 minutes; Days 1 and 15
Other Names:
PO twice daily (BID); Days 1-7, 15-21
Other Names:
IV over 60 minutes; Days 1 and 15
Other Names:
IV over 30 minutes; Days 1 and 15
Other Names:
IV over 30 minutes; Days 4 and 11
Other Names:
IV over 30 minutes; Days 4 and 11
Other Names:
PO BID; Days 1- 14
Other Names:
IV over 60 minutes; Days 4 and 11
Other Names:
IV over 30 minutes; Days 4 and 11
Other Names:
|
|
Experimental: Phase 2 Dose Expansion (Cohort 1, DL5)
Gemcitabine:500 mg/m^2, IV over 30 minutes; Days 1 and 15 of a 28 day cycle Nab-paclitaxel:125 mg/m^2, IV over 30 minutes; Days 1 and 15 of a 28 day cycle Capecitabine: 500 mg BID, PO twice daily (BID); Days 1-7, 15-21 of a 28 day cycle Cisplatin:20 mg/m^2, IV over 60 minutes; Days 1 and 15 of a 28 day cycle Irinotecan: 20 mg/m^2, IV over 30 minutes; Days 1 and 15 of a 28 day cycle |
IV over 30 minutes; Days 1 and 15
Other Names:
IV over 30 minutes; Days 1 and 15
Other Names:
PO twice daily (BID); Days 1-7, 15-21
Other Names:
IV over 60 minutes; Days 1 and 15
Other Names:
IV over 30 minutes; Days 1 and 15
Other Names:
IV over 30 minutes; Days 4 and 11
Other Names:
IV over 30 minutes; Days 4 and 11
Other Names:
PO BID; Days 1- 14
Other Names:
IV over 60 minutes; Days 4 and 11
Other Names:
IV over 30 minutes; Days 4 and 11
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
|
Maximum Tolerated Dose (MTD) of Gemcitabine.
Time Frame: 28 days
|
Dose escalation (phase I portion of the trial only) to determine the MTD in mg/m^2.
Participants received Gemcitabine: 500 mg/m^2, IV over 30 minutes; Days 1 and 15 of a 28 day cycle (Cohort 1) or Days 4 and 11 of a 21 day cycle (Cohort 2)
|
28 days
|
|
Maximum Tolerated Dose (MTD) of Nab-paclitaxel.
Time Frame: 28 days
|
Dose escalation (phase I portion of the trial only) to determine the MTD in mg/m^2.
Participants received Nab-paclitaxel: 20, 40, 60, 80, 100,125 mg/m^2, IV over 30 minutes; Days 1 and 15 of a 28 day cycle (Cohort 1) or Days 4 and 11 of a 21 day cycle (Cohort 2)
|
28 days
|
|
Maximum Tolerated Dose (MTD) of Capecitabine.
Time Frame: 28 days
|
Dose escalation (phase I portion of the trial only) to determine the MTD in mg for twice daily (BID) use.
Participants received Capecitabine: 500 mg BID, PO twice daily (BID); Days 1-7, 15-21 of a 28 day cycle (Cohort 1) or Days 1-14 of a 21 day cycle (Cohort 2)
|
28 days
|
|
Maximum Tolerated Dose (MTD) of Cisplatin.
Time Frame: 28 days
|
Dose escalation (phase I portion of the trial only) to determine the MTD in mg/m^2.
Participants received Cisplatin:20 mg/m^2, IV over 60 minutes; Days 1 and 15 of a 28 day cycle (Cohort 1) or Days 4 and 11 of a 21 day cycle (Cohort 2)
|
28 days
|
|
Maximum Tolerated Dose (MTD) of Irinotecan.
Time Frame: 28 days
|
Dose escalation (phase I portion of the trial only) to determine the MTD in mg/m^2.
Participants received Irinotecan: 20 mg/m^2, IV over 30 minutes; Days 1 and 15 of a 28 day cycle (Cohort 1) or Days 4 and 11 of a 21 day cycle (Cohort 2)
|
28 days
|
|
Progression-free Survival (PFS) Using RECIST 1.1 Criteria
Time Frame: 27 months
|
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.
|
27 months
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
|
Safety of the Combination of Gemcitabine, Nab-paclitaxel, Capecitabine, Cisplatin, and Irinotecan (GAX-CI) in Patients With Untreated Metastatic PDA.
Time Frame: 27 months
|
Number of patients who received the MTD (Cohort 1, Dose Level 5) that experienced a limiting toxicity.
Limiting toxicity was defined as a grade 3 or above treatment-related toxicity, with the following exceptions: 1. Grade 3 anemia that resolves to < grade 2 within 7 days; 2. Grade 3 thrombocytopenia without clinically significant bleeding that resolves to < grade 2 within 7 days; 3. Grade 3 or 4 neutropenia that resolves to <grade 2 within 7 days; 4. Grade 3 or 4 leucopenia/lymphopenia; 5. Grade 3 nausea, vomiting, or diarrhea that resolves to <grade 2 within 72 hours; 6. Grade 3 or 4 asymptomatic laboratory values that resolve to < grade 2 within 7 days; 7. Grade 3 dermatologic AEs that are considered mild in severity but only considered grade 3 because of >30% body surface involvement; 8. Grade 3 fatigue lasting less than 72 hours.
This study used the descriptions and grading scales found in the revised NCI CTCAE fV 5.0 for adverse event reporting.
|
27 months
|
Collaborators and Investigators
Investigators
- Principal Investigator: Dung Le, MD, Johns Hopkins Medical Institution
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Neoplasms by Site
- Neoplasms by Histologic Type
- Neoplasms
- Gastrointestinal Diseases
- Digestive System Diseases
- Pancreatic Neoplasms
- Gastrointestinal Neoplasms
- Neoplasms, Glandular and Epithelial
- Digestive System Neoplasms
- Endocrine System Diseases
- Endocrine Gland Neoplasms
- Pancreatic Diseases
- Antineoplastic Agents
- Molecular Mechanisms of Pharmacological Action
- Enzyme Inhibitors
- Antimetabolites, Antineoplastic
- Antimetabolites
- Tubulin Modulators
- Antimitotic Agents
- Mitosis Modulators
- Topoisomerase I Inhibitors
- Topoisomerase Inhibitors
- Antineoplastic Agents, Phytogenic
- Capecitabine
- Irinotecan
- Albumin-Bound Paclitaxel
- Gemcitabine
- Paclitaxel
- Cisplatin
Other Study ID Numbers
- J1847
- IRB00167664 (Other Identifier: Johns Hopkins Medical Institution)
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
product manufactured in and exported from the U.S.
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