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Gemcitabine, Nab-paclitaxel, Capecitabine, Cisplatin, and Irinotecan in Treating Patients with Pancreatic Cancer That Has Spread to Other Places in the Body

Trial Status: Active

This phase I / II trial studies the side effects and best dose of nab-paclitaxel in combination with gemcitabine, capecitabine, cisplatin, and irinotecan and how well they work in treating patients with pancreatic cancer that has spread to other parts of the body. Drugs used in chemotherapy, such as gemcitabine, nab-paclitaxel, capecitabine, cisplatin, and irinotecan, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading.

Inclusion Criteria

  • Subjects must have histologically or cytologically confirmed untreated metastatic pancreatic adenocarcinoma. Subjects with islet cell neoplasms are excluded. Subjects with mixed histology will be excluded
  • Subject has one or more tumors measurable by computed tomography (CT) scan using Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria. Magnetic resonance imaging (MRI) is acceptable if a CT scan is contraindicated.
  • Male or non-pregnant and non-lactating female.
  • Eastern Cooperative Oncology Group (ECOG) performance status =< 1. ECOG 0 indicates that the patient is fully active and able to carry on all pre-disease activities without restriction; and, ECOG 1 indicates that the patient is restricted in physically strenuous activity but is ambulatory and able to carry out work of a light or sedentary nature.
  • Absolute neutrophil count >= 1,500/mcL.
  • Platelets >= 100 x 10^9/L.
  • Hemoglobin >= 8 g/dL.
  • Total bilirubin within normal institutional limits (=< 1.5 X upper limit of normal [ULN] if resolving biliary obstruction).
  • Alkaline phosphatase =< 5 X ULN.
  • Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 x ULN (=< 5 X ULN for subjects with documented liver metastases).
  • Creatinine within normal limits (creatinine clearance >= 60 mL/min/1.73 m^2 for subjects with creatinine levels above institutional normal.)
  • Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately.
  • Ability to understand and the willingness to sign a written informed consent document.

Exclusion Criteria

  • Patients who will be considered for surgery are ineligible.
  • Subjects who have had any prior chemotherapy for pancreatic cancer or prior chemotherapy within 5 years of enrollment for other cancer diagnoses.
  • Subjects who have had radiotherapy for pancreatic cancer.
  • Subjects who are receiving or have received any other investigational agents within 28 days prior to day 1 of treatment in this study.
  • Subject has undergone major surgery, other than diagnostic surgery (i.e. surgery done to obtain a biopsy for diagnosis or an aborted Whipple), within 28 days prior to day 1 of treatment in this study.
  • Subject has known brain metastases.
  • History of hypersensitivity or allergic reactions attributed to compounds of similar chemical or biologic composition to gemcitabine, nab-paclitaxel, capecitabine, cisplatin, or irinotecan.
  • 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.
  • Subject has serious medical risk factors involving any of the major organ systems such that the investigator considers it unsafe for the subject to receive an experimental research drug.
  • Subject has a known history of infection with human immunodeficiency virus (HIV), hepatitis B, or hepatitis C.
  • Subject is pregnant or breast feeding.
  • Subject is unwilling or unable to comply with study procedures.
  • Subject with clinically significant wound.

Maryland

Baltimore
Johns Hopkins University / Sidney Kimmel Cancer Center
Status: ACTIVE
Contact: Dung Thi Le
Phone: 443-287-0002
Email: Dle@jhmi.edu

PRIMARY OBJECTIVES:

I. To assess safety of the combination of gemcitabine, nab-paclitaxel, capecitabine, cisplatin, and irinotecan (GAX-CI) in patients with untreated metastatic pancreatic adenocarcinoma (PDA) and to determine the maximally tolerated dose (MTD) or the recommended dose for phase II of the combination. (Phase I, Part 1)

II. To assess the efficacy of the combination of gemcitabine, nab-paclitaxel, capecitabine, cisplatin, and irinotecan (GAX-CI) in patients with untreated metastatic PDA based on the progression free survival (PFS). (Phase II, Part 2)

SECONDARY OBJECTIVES:

I. To estimate the response rate (RR), disease control rate (DCR), and overall survival (OS) of the combination of gemcitabine, nab-paclitaxel, capecitabine, cisplatin, and irinotecan (GAX-CI) in patients with untreated metastatic PDA. (Part 2)

II. Continue to assess the safety of GAX-CI in patients with untreated metastatic PDA. (Part 2)

EXPLORATORY OBJECTIVES:

I. To assess tumor burden dynamics using both standard protein biomarkers such as CA19-9 and CEA and exploratory biomarkers such as circulating tumor deoxyribonucleic acid (DNA).

II. To assess baseline characteristics of the patients enrolled and correlate these molecular and clinicopathologic criteria with treatment response and toxicity.

OUTLINE: This is a dose escalation study of nab-paclitaxel, followed by a phase II dose expansion study. Patients are sequentially assigned to 1 of 2 cohorts.

COHORT 1: Patients receive nab-paclitaxel intravenously (IV) over 30 minutes, gemcitabine IV over 30 minutes, cisplatin IV over 60 minutes, and irinotecan IV over 30 minutes on days 1 and 15. Patients also receive capecitabine orally (PO) twice daily (BID) on days 1-7 and 15-21. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

COHORT 2: Patients receive nab-paclitaxel IV over 30 minutes, gemcitabine IV over 30 minutes, cisplatin IV over 60 minutes, and irinotecan IV over 30 minutes on days 4 and 11. Patients also receive capecitabine PO BID on days 1-14. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed for 28 days and then every 3 months thereafter.

Trial Phase Phase I/II

Trial Type Treatment

Lead Organization
Johns Hopkins University / Sidney Kimmel Cancer Center

Principal Investigator
Dung Thi Le

  • Primary ID J1847
  • Secondary IDs NCI-2018-03188, CRMS-68854, IRB00167664
  • Clinicaltrials.gov ID NCT03535727