A Study Of Gemcitabine, Nab-paclitaxel, Capecitabine, Cisplatin, And Irinotecan In Metastatic Pancreatic Cancer

Study Overview

A Study of Gemcitabine, Nab-paclitaxel, Capecitabine, Cisplatin, and Irinotecan in Metastatic Pancreatic Cancer

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.

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.

Adenocarcinoma
Pancreatic Neoplasms
Neoplasm, Glandular
Neoplasms
Neoplasms Pancreatic
Digestive System Neoplasm
Endocrine Gland Neoplasms
Digestive System Disease
Pancreatic Diseases
Endocrine System Diseases

DRUG: Nab-paclitaxel
DRUG: Gemcitabine
DRUG: Capecitabine
DRUG: Cisplatin
DRUG: Irinotecan
DRUG: Nab-paclitaxel
DRUG: Gemcitabine
DRUG: Capecitabine
DRUG: Cisplatin
DRUG: Irinotecan

J1847
IRB00167664 (OTHER Identifier) (OTHER: Johns Hopkins Medical Institution)

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates	Results Reporting Dates	Study Record Updates
First Submitted 2018-05-11	Results First Submitted 2023-09-15	Last Update Submitted that met QC Criteria 2024-12-13
First Submitted that Met QC Criteria 2018-05-22	Results First Submitted that Met QC Criteria 2024-01-02	Last Update Posted (ACTUAL) 2024-12-31
First Posted (ACTUAL) 2018-05-24	Results First Posted 2024-01-08	Last Verified 2024-12

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

Design Details

Primary Purpose:
Treatment

Allocation:
Non Randomized

Interventional Model:
Sequential

Masking:
None

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	DRUG: Nab-paclitaxel IV over 30 minutes; Days 1 and 15 DRUG: Gemcitabine IV over 30 minutes; Days 1 and 15 DRUG: Capecitabine PO twice daily (BID); Days 1-7, 15-21 DRUG: Cisplatin IV over 60 minutes; Days 1 and 15 DRUG: Irinotecan IV over 30 minutes; Days 1 and 15
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	DRUG: Nab-paclitaxel IV over 30 minutes; Days 1 and 15 DRUG: Gemcitabine IV over 30 minutes; Days 1 and 15 DRUG: Capecitabine PO twice daily (BID); Days 1-7, 15-21 DRUG: Cisplatin IV over 60 minutes; Days 1 and 15 DRUG: Irinotecan IV over 30 minutes; Days 1 and 15
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 m	DRUG: Nab-paclitaxel IV over 30 minutes; Days 1 and 15 DRUG: Gemcitabine IV over 30 minutes; Days 1 and 15 DRUG: Capecitabine PO twice daily (BID); Days 1-7, 15-21 DRUG: Cisplatin IV over 60 minutes; Days 1 and 15 DRUG: Irinotecan IV over 30 minutes; Days 1 and 15
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	DRUG: Nab-paclitaxel IV over 30 minutes; Days 1 and 15 DRUG: Gemcitabine IV over 30 minutes; Days 1 and 15 DRUG: Capecitabine PO twice daily (BID); Days 1-7, 15-21 DRUG: Cisplatin IV over 60 minutes; Days 1 and 15 DRUG: Irinotecan IV over 30 minutes; Days 1 and 15
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	DRUG: Nab-paclitaxel IV over 30 minutes; Days 1 and 15 DRUG: Gemcitabine IV over 30 minutes; Days 1 and 15 DRUG: Capecitabine PO twice daily (BID); Days 1-7, 15-21 DRUG: Cisplatin IV over 60 minutes; Days 1 and 15 DRUG: Irinotecan IV over 30 minutes; Days 1 and 15
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, I	DRUG: Nab-paclitaxel IV over 30 minutes; Days 4 and 11 DRUG: Gemcitabine IV over 30 minutes; Days 4 and 11 DRUG: Capecitabine PO BID; Days 1- 14 DRUG: Cisplatin IV over 60 minutes; Days 4 and 11 DRUG: Irinotecan IV over 30 minutes; Days 4 and 11
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	DRUG: Nab-paclitaxel IV over 30 minutes; Days 4 and 11 DRUG: Gemcitabine IV over 30 minutes; Days 4 and 11 DRUG: Capecitabine PO BID; Days 1- 14 DRUG: Cisplatin IV over 60 minutes; Days 4 and 11 DRUG: Irinotecan IV over 30 minutes; Days 4 and 11
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	DRUG: Nab-paclitaxel IV over 30 minutes; Days 4 and 11 DRUG: Gemcitabine IV over 30 minutes; Days 4 and 11 DRUG: Capecitabine PO BID; Days 1- 14 DRUG: Cisplatin IV over 60 minutes; Days 4 and 11 DRUG: Irinotecan IV over 30 minutes; Days 4 and 11
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	DRUG: Nab-paclitaxel IV over 30 minutes; Days 1 and 15 DRUG: Gemcitabine IV over 30 minutes; Days 1 and 15 DRUG: Capecitabine PO twice daily (BID); Days 1-7, 15-21 DRUG: Cisplatin IV over 60 minutes; Days 1 and 15 DRUG: Irinotecan IV over 30 minutes; Days 1 and 15

Primary Outcome Measures	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. 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.	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.	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.	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.	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	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	Measure Description	Time Frame
Safety of the Combination of Gemcitabine, Nab-paclitaxel, Capecitabine, Cisplatin, and Irinotecan (GAX-CI) in Patients With Untreated Metastatic PDA.	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 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

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person’s general health condition or prior treatments.

Ages Eligible for Study:
ALL

Sexes Eligible for Study:
18 Years

Accepts Healthy Volunteers:

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.

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.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Investigators

PRINCIPAL_INVESTIGATOR: Dung Le, MD, Johns Hopkins Medical Institution

Publications

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

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Clinical Trial Record