A Phase I/II Study of Gemcitabine, Nab-paclitaxel, Capecitabine, Cisplatin, and Irinotecan (GAX-CI) in Combination in Metastatic Pancreatic Cancer
Overview
- Phase
- Phase 1
- Intervention
- Nab-paclitaxel
- Conditions
- Adenocarcinoma
- Sponsor
- Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
- Enrollment
- 48
- Locations
- 1
- Primary Endpoint
- Maximum Tolerated Dose (MTD) of Gemcitabine.
- Status
- Completed
- Last Updated
- last year
Overview
Brief Summary
The purpose of this study is to evaluate the clinical activity of gemcitabine, nab-paclitaxel, capecitabine, cisplatin, and irinotecan (GAX-CI) in patients with metastatic pancreatic cancer.
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.
Investigators
Eligibility Criteria
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
- •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.
Arms & Interventions
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
Intervention: Nab-paclitaxel
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
Intervention: Gemcitabine
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
Intervention: Capecitabine
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
Intervention: Cisplatin
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
Intervention: Irinotecan
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
Intervention: Nab-paclitaxel
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
Intervention: Gemcitabine
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
Intervention: Capecitabine
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
Intervention: Cisplatin
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
Intervention: Irinotecan
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
Intervention: Nab-paclitaxel
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
Intervention: Gemcitabine
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
Intervention: Capecitabine
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
Intervention: Cisplatin
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
Intervention: Irinotecan
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
Intervention: Nab-paclitaxel
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
Intervention: Gemcitabine
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
Intervention: Capecitabine
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
Intervention: Cisplatin
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
Intervention: Irinotecan
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
Intervention: Nab-paclitaxel
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
Intervention: Gemcitabine
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
Intervention: Capecitabine
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
Intervention: Cisplatin
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
Intervention: Irinotecan
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
Intervention: Nab-paclitaxel
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
Intervention: Gemcitabine
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
Intervention: Capecitabine
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
Intervention: Cisplatin
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
Intervention: Irinotecan
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
Intervention: Nab-paclitaxel
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
Intervention: Gemcitabine
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
Intervention: Capecitabine
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
Intervention: Cisplatin
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
Intervention: Irinotecan
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
Intervention: Nab-paclitaxel
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
Intervention: Gemcitabine
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
Intervention: Capecitabine
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
Intervention: Cisplatin
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
Intervention: Irinotecan
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
Intervention: Nab-paclitaxel
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
Intervention: Gemcitabine
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
Intervention: Capecitabine
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
Intervention: Cisplatin
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
Intervention: Irinotecan
Outcomes
Primary Outcomes
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)
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)
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)
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)
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)
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.
Secondary Outcomes
- Safety of the Combination of Gemcitabine, Nab-paclitaxel, Capecitabine, Cisplatin, and Irinotecan (GAX-CI) in Patients With Untreated Metastatic PDA.(27 months)