Clinical trial NCT03535727: A Study of Gemcitabine, Nab-paclitaxel, Capecitabine, Cisplatin, and Irinotecan in Metastatic Pancreatic Cancer
Official title: A Phase I/II Study of Gemcitabine, Nab-paclitaxel, Capecitabine, Cisplatin, and Irinotecan (GAX-CI) in Combination in Metastatic Pancreatic Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Adenocarcinoma
Pancreatic Neoplasms
Neoplasm, Glandular
Neoplasms
Neoplasms Pancreatic
Digestive System Neoplasm
Endocrine Gland Neoplasms
Digestive System Disease
Pancreatic Diseases
Endocrine System Diseases
Lead sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Sponsor class: OTHER
First posted: 2018-05-24
Enrollment: 48
Sex: ALL
Minimum age (years): 18
Maximum age (years): 76
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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.

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 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.

Primary outcomes:
measure: Maximum Tolerated Dose (MTD) of Gemcitabine.
timeFrame: 28 days
measure: Maximum Tolerated Dose (MTD) of Nab-paclitaxel.
timeFrame: 28 days
measure: Maximum Tolerated Dose (MTD) of Capecitabine.
timeFrame: 28 days
measure: Maximum Tolerated Dose (MTD) of Cisplatin.
timeFrame: 28 days
measure: Maximum Tolerated Dose (MTD) of Irinotecan.
timeFrame: 28 days
measure: Progression-free Survival (PFS) Using RECIST 1.1 Criteria
timeFrame: 27 months
Secondary outcomes:
measure: Safety of the Combination of Gemcitabine, Nab-paclitaxel, Capecitabine, Cisplatin, and Irinotecan (GAX-CI) in Patients With Untreated Metastatic PDA.
timeFrame: 27 months
Other outcomes:
Locations:
city: Baltimore
country: United States
facility: Sidney Kimmel Comprehensive Cancer Center
state: Maryland
Study officials:
affiliation: Johns Hopkins Medical Institution
name: Dung Le, MD
role: PRINCIPAL_INVESTIGATOR
References: