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

NCT03535727 | Completed Phase 1 Results DMC FDA Drug

• 2 other identifiers: J1847IRB00167664
• Study Type: interventional
• Target: 48
• Locations: 1 country
• Sites: 1

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.

Conditions

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

Outcome Measures

Primary Outcomes (6)

• 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 Outcomes (1)

• Safety of the Combination of Gemcitabine, Nab-paclitaxel, Capecitabine, Cisplatin, and Irinotecan (GAX-CI) in Patients With Untreated Metastatic PDA.

  27 months

Study Arms (9)

Phase 1, Cohort 1, Dose level 1

EXPERIMENTAL

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

Drug: Nab-paclitaxel; Drug: Gemcitabine; Drug: Capecitabine; Drug: Cisplatin; Drug: Irinotecan

Phase 1, Cohort 1, Dose level 2

EXPERIMENTAL

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

Drug: Nab-paclitaxel; Drug: Gemcitabine; Drug: Capecitabine; Drug: Cisplatin; Drug: Irinotecan

Phase 1, Cohort 1, Dose level 3

EXPERIMENTAL

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

Drug: Nab-paclitaxel; Drug: Gemcitabine; Drug: Capecitabine; Drug: Cisplatin; Drug: Irinotecan

Phase 1, Cohort 1, Dose level 4

EXPERIMENTAL

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

Drug: Nab-paclitaxel; Drug: Gemcitabine; Drug: Capecitabine; Drug: Cisplatin; Drug: Irinotecan

Phase 1, Cohort 1, Dose level 5

EXPERIMENTAL

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

Drug: Nab-paclitaxel; Drug: Gemcitabine; Drug: Capecitabine; Drug: Cisplatin; Drug: Irinotecan

Phase 1, Cohort 2, Dose level 1

EXPERIMENTAL

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

Drug: Nab-paclitaxel; Drug: Gemcitabine; Drug: Capecitabine; Drug: Cisplatin; Drug: Irinotecan

Phase 1, Cohort 2, Dose level 2

EXPERIMENTAL

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

Drug: Nab-paclitaxel; Drug: Gemcitabine; Drug: Capecitabine; Drug: Cisplatin; Drug: Irinotecan

Phase 1, Cohort 2, Dose level 3

EXPERIMENTAL

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

Drug: Nab-paclitaxel; Drug: Gemcitabine; Drug: Capecitabine; Drug: Cisplatin; Drug: Irinotecan

Phase 2 Dose Expansion (Cohort 1, DL5)

EXPERIMENTAL

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

Drug: Nab-paclitaxel; Drug: Gemcitabine; Drug: Capecitabine; Drug: Cisplatin; Drug: Irinotecan

Interventions

Nab-paclitaxel DRUG

IV over 30 minutes; Days 1 and 15

Also known as: Abraxane

Phase 1, Cohort 1, Dose level 1; Phase 1, Cohort 1, Dose level 2; Phase 1, Cohort 1, Dose level 3; Phase 1, Cohort 1, Dose level 4; Phase 1, Cohort 1, Dose level 5; Phase 2 Dose Expansion (Cohort 1, DL5)

Gemcitabine DRUG

IV over 30 minutes; Days 1 and 15

Also known as: Gemzar

Phase 1, Cohort 1, Dose level 1; Phase 1, Cohort 1, Dose level 2; Phase 1, Cohort 1, Dose level 3; Phase 1, Cohort 1, Dose level 4; Phase 1, Cohort 1, Dose level 5; Phase 2 Dose Expansion (Cohort 1, DL5)

Capecitabine DRUG

PO twice daily (BID); Days 1-7, 15-21

Also known as: Xeloda

Phase 1, Cohort 1, Dose level 1; Phase 1, Cohort 1, Dose level 2; Phase 1, Cohort 1, Dose level 3; Phase 1, Cohort 1, Dose level 4; Phase 1, Cohort 1, Dose level 5; Phase 2 Dose Expansion (Cohort 1, DL5)

Cisplatin DRUG

IV over 60 minutes; Days 1 and 15

Also known as: Platinol

Phase 1, Cohort 1, Dose level 1; Phase 1, Cohort 1, Dose level 2; Phase 1, Cohort 1, Dose level 3; Phase 1, Cohort 1, Dose level 4; Phase 1, Cohort 1, Dose level 5; Phase 2 Dose Expansion (Cohort 1, DL5)

Irinotecan DRUG

IV over 30 minutes; Days 1 and 15

Also known as: Camptosar

Phase 1, Cohort 1, Dose level 1; Phase 1, Cohort 1, Dose level 2; Phase 1, Cohort 1, Dose level 3; Phase 1, Cohort 1, Dose level 4; Phase 1, Cohort 1, Dose level 5; Phase 2 Dose Expansion (Cohort 1, DL5)

Eligibility Criteria

• Age: 18 Years - 76 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins: lead

Study Sites (1)

Sidney Kimmel Comprehensive Cancer Center

Baltimore, Maryland, 21231, United States

Location

MeSH Terms

Conditions

Adenocarcinoma; Pancreatic Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms; Digestive System Neoplasms; Endocrine Gland Neoplasms; Digestive System Diseases; Pancreatic Diseases; Endocrine System Diseases

Interventions

130-nm albumin-bound paclitaxel; Albumin-Bound Paclitaxel; Gemcitabine; Capecitabine; Cisplatin; Irinotecan

Condition Hierarchy (Ancestors)

Carcinoma; Neoplasms by Histologic Type; Neoplasms by Site

Intervention Hierarchy (Ancestors)

Paclitaxel; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Albumins; Proteins; Amino Acids, Peptides, and Proteins; Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Fluorouracil; Uracil; Pyrimidinones; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Camptothecin; Alkaloids

Results Point of Contact

• Title: Dung Le, M.D.
• Organization: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Dle@jhmi.edu

443-287-0002

Study Officials

• Dung Le, MD

  Johns Hopkins Medical Institution

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 11, 2018
• First Posted: May 24, 2018
• Study Start: June 21, 2018
• Primary Completion: October 3, 2022
• Study Completion: October 3, 2022
• Last Updated: December 31, 2024
• Results First Posted: January 8, 2024

Record last verified: 2024-12

Locations

US (1)