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

Neoplasms Clinical Trial

Official title:

A Phase I/II Study of Gemcitabine, Nab-paclitaxel, Capecitabine, Cisplatin, and Irinotecan (GAX-CI) in Combination in Metastatic Pancreatic Cancer

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03535727
• Other study ID #: J1847
• Secondary ID: IRB00167664
• Status: Completed
• Phase: Phase 1/Phase 2
• Start date: June 21, 2018
• Est. completion date: October 3, 2022

Study information

• Verified date: January 2024
• Source: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 48
• Est. completion date: October 3, 2022
• Est. primary completion date: October 3, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 76 Years

Eligibility

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.

Related Conditions & MeSH terms

• Adenocarcinoma
• Digestive System Disease
• Digestive System Diseases
• Digestive System Neoplasm
• Digestive System Neoplasms
• Endocrine Gland Neoplasms
• Endocrine System Diseases
• Gastrointestinal Diseases
• Gastrointestinal Neoplasms
• Neoplasm, Glandular
• Neoplasms
• Neoplasms Pancreatic
• Neoplasms, Glandular and Epithelial
• Pancreatic Diseases
• Pancreatic Neoplasms

Intervention

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

Locations

Country	Name	City	State
United States	Sidney Kimmel Comprehensive Cancer Center	Baltimore	Maryland

Sponsors (1)

Lead Sponsor	Collaborator
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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	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	27 months