Nab-Paclitaxel, Capecitabine, And Radiation Therapy Following Induction Chemotherapy In Treating Patients With Locally Advanced Pancreatic Cancer

Study Overview

Nab-Paclitaxel, Capecitabine, and Radiation Therapy Following Induction Chemotherapy in Treating Patients With Locally Advanced Pancreatic Cancer

This phase I trial studies the side effects and best dose of nab-paclitaxel when given together with capecitabine and radiation therapy following first treatment with chemotherapy (induction therapy) in treating patients with pancreatic cancer that is not spread to tissue far away but is not operable due to abutment or encasement of blood vessels nearby (locally advanced). Drugs used in chemotherapy, such as nab-paclitaxel and capecitabine, 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. Radiation therapy uses high-energy x-rays to kill tumor cells and shrink tumors. Giving nab-paclitaxel, capecitabine, and radiation therapy together may kill more tumor cells.

PRIMARY OBJECTIVES: I. To evaluate the safety and tolerability of combining nab-paclitaxel (abraxane) with capecitabine and radiation (radiation therapy) for consolidating treatment after induction chemotherapy for locally advanced pancreatic cancer. SECONDARY OBJECTIVES: I. To evaluate whether combining abraxane with capecitabine and radiation for consolidating treatment after induction chemotherapy for locally advanced pancreatic cancer increases overall survival. II. To analyze fine needle aspiration (FNA) or core needle biopsy samples for mothers against decapentaplegic homolog 4 (SMAD4) by immunocytochemistry. III. To evaluate plasma cytokines levels, circulating tumor cells before, during and after therapy. IV. To evaluate patient-reported symptoms using the MD Anderson Symptom Inventory Gastrointestinal Cancer Module (MDASI-GI). V. To evaluate response rate in patients treated at the maximum tolerated dose (MTD). OUTLINE: This is a dose-escalation study of nab-paclitaxel. Patients receive nab-paclitaxel intravenously (IV) over 30 minutes on days 1, 8, 15, 22, and 29 and capecitabine orally (PO) twice daily (BID) on days 1-5 (Monday-Friday). Patients also undergo radiation therapy once daily (QD) on days 1-5 (Monday-Friday). Treatment continues for 5 1/2 weeks in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up at 4-6 weeks and then every 3 months.

Borderline Resectable Pancreatic Adenocarcinoma
Locally Advanced Pancreatic Adenocarcinoma
Pancreatic Adenocarcinoma
Stage II Pancreatic Cancer AJCC v6 and v7
Stage IIA Pancreatic Cancer AJCC v6 and v7
Stage IIB Pancreatic Cancer AJCC v6 and v7
Stage III Pancreatic Cancer AJCC v6 and v7

DRUG: Capecitabine
OTHER: Laboratory Biomarker Analysis
DRUG: Nab-paclitaxel
OTHER: Questionnaire Administration
RADIATION: Radiation Therapy

2014-0469
NCI-2015-00516 (REGISTRY Identifier) (REGISTRY: CTRP (Clinical Trial Reporting Program))
2014-0469 (OTHER Identifier) (OTHER: M D Anderson Cancer Center)

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 2015-03-16	Results First Submitted N/A	Last Update Submitted that met QC Criteria 2022-08-31
First Submitted that Met QC Criteria 2015-03-16	Results First Submitted that Met QC Criteria N/A	Last Update Posted (ACTUAL) 2022-09-02
First Posted (ACTUAL) 2015-03-20	Results First Posted N/A	Last Verified 2022-08

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:
Na

Interventional Model:
Single Group

Masking:
None

Arms and Interventions

Participant Group/Arm	Intervention/Treatment
EXPERIMENTAL: Treatment (chemotherapy, radiation therapy) Patients receive nab-paclitaxel IV over 30 minutes on days 1, 8, 15, 22, and 29 and capecitabine PO BID on days 1-5 (Monday-Friday). Patients also undergo radiation therapy QD on days 1-5 (Monday-Friday). Treatment continues for 51/2 weeks in the absence	DRUG: Capecitabine Given PO OTHER: Laboratory Biomarker Analysis Correlative studies DRUG: Nab-paclitaxel Given IV OTHER: Questionnaire Administration Ancillary studies RADIATION: Radiation Therapy Undergo radiation therapy

Participant Group/Arm

Intervention/Treatment

EXPERIMENTAL: Treatment (chemotherapy, radiation therapy)

Patients receive nab-paclitaxel IV over 30 minutes on days 1, 8, 15, 22, and 29 and capecitabine PO BID on days 1-5 (Monday-Friday). Patients also undergo radiation therapy QD on days 1-5 (Monday-Friday). Treatment continues for 51/2 weeks in the absence

DRUG: Capecitabine

Given PO

OTHER: Laboratory Biomarker Analysis

Correlative studies

DRUG: Nab-paclitaxel

Given IV

OTHER: Questionnaire Administration

Ancillary studies

RADIATION: Radiation Therapy

Undergo radiation therapy

Primary Outcome Measures	Measure Description	Time Frame
Maximum tolerated dose defined as the highest dose level in which 6 patients have been treated with at most 1 instance of dose limiting toxicity (DLT) according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0	Descriptive statistics will be used to summarize will be used to summarize patient demographic and clinical characteristics as well as the incidence of DLTs at each dose level.	4-6 weeks

Secondary Outcome Measures	Measure Description	Time Frame
Overall survival	The probabilities of overall survival will be estimated using the method of Kaplan and Meier.	Up to 4 years
Response rate	The response rate for patients treated at the maximum tolerated dose will be estimated, along with the exact 95% confidence interval.	Up to 4 years
Changes in MD Anderson Symptom Inventory Gastrointestinal Cancer Module (MDASI)	Descriptive statistics will be used to summarize patients' MDASI data. Paired t-test or Wilcoxon sign rank test will be used to assess the change of MDASI from baseline.	Baseline to up to 4 years

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:
19 Years

Accepts Healthy Volunteers:

Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
Cytologic or histologic proof of adenocarcinoma of the pancreas; patients can have tumor which is locally advanced or borderline resectable; unequivocal metastases and islet cell tumors are not eligible
All patients must be staged with a physical exam, computed tomography (CT) of the chest and contrast-enhanced helical thin-cut abdominal CT; unresectability is defined by CT criteria:

Evidence of tumor extension to the celiac axis or superior mesenteric (SM) artery, or
Evidence on either CT or angiogram of occlusion of the SM vein or SM/portal vein confluence
Patients must have received prior induction chemotherapy for at least 2 months and up to 8 months; at least three weeks should have elapsed after the last chemotherapy
Platelets > 100,000 cells/mm^3
Hemoglobin > 9.0 g/dL
Absolute neutrophil count (ANC) >= 1,500 cells/mm^3
Bilirubin =< 1.5 mg/dL
Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) < 2.5 x upper limit of normal
Alkaline phosphatase < 2.5 x upper limit of normal
Blood urea nitrogen (BUN) < 30 mg/dL
Creatinine =< 1.5 mg/dL or creatinine clearance > 30 ml/min (estimated as calculated with Cockcroft-Gault equation)
Patients must have signed informed consent indicating that they are aware of the investigational nature of the study, and are aware that participation is voluntary
Patients must have < grade 2 pre-existing peripheral neuropathy (per Common Terminology Criteria for Adverse Events [CTCAE])
Patients must have recovery from other clinically significant, non-hematologic toxicities to =< grade 2
Women of childbearing potential and sexually active males must use an effective contraception method during treatment and for three months after completing treatment
Negative serum or urine beta-human chorionic gonadotropin (hCG) pregnancy test at screening for female patients of childbearing potential

Prior abdominal radiotherapy
Current, recent (within 4 weeks of the first infusion of this study), or planned participation in any other experimental drug study
Prior severe infusion reaction (bronchospasm, stridor, urticaria and/or hypotension) to a taxane therapy
Prior unanticipated severe reaction to fluoropyrimidine therapy or known hypersensitivity to 5-fluorouracil
Prior history of cancer within the last three years except for basal cell carcinoma of the skin or carcinoma in situ of the cervix; patients with previous malignancies but without evidence of disease for 3 years will be allowed to enter the trial
Pregnant or lactating women; women of childbearing potential with either a positive or no pregnancy test at baseline; women/men of childbearing potential not using a reliable contraceptive method (oral contraceptive, other hormonal contraceptive, intrauterine device, diaphragm or condom); (postmenopausal women must have been amenorrheic for at least 12 months to be considered of non-childbearing potential); patients must agree to continue contraception for 30 days from the date of the last study drug administration
Lack of physical integrity of the upper gastrointestinal tract, malabsorption syndrome or inability to swallow
Known, existing uncontrolled coagulopathy, international normalized ratio (INR) > 1.5
Patients on Coumadin must be changed to Lovenox at least 1 week prior to starting capecitabine; low dose (1 mg) Coumadin is allowed; intravenous and low-molecular weight heparin are permitted
Patients taking sorivudine or brivudine must be off of these drugs for 4 weeks prior to starting capecitabine; patients taking cimetidine must have this drug discontinued; ranitidine or a drug from another anti-ulcer class can be substituted for cimetidine if necessary; if patient is currently receiving allopurinol, must discuss with principal investigator (PI) to see of another agent may substitute for it
Inability to comply with study and/or follow-up procedures
History of interstitial lung disease, history of slowly progressive dyspnea and unproductive cough, sarcoidosis, silicosis, idiopathic pulmonary fibrosis or pulmonary hypersensitivity pneumonitis

Collaborators and Investigators

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

National Cancer Institute (NCI)

Investigators

PRINCIPAL_INVESTIGATOR: Eugene J Koay, MD,PHD, M.D. Anderson Cancer Center

Publications

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

General Publications

Koay EJ, Zaid M, Aliru M, Bagereka P, Van Wieren A, Rodriguez MJ, Jacobson G, Wolff RA, Overman M, Varadhachary G, Pant S, Wang H, Tzeng CW, Ikoma N, Kim M, Lee JE, Katz MH, Tamm E, Bhosale P, Taniguchi CM, Holliday EB, Smith GL, Ludmir EB, Minsky BD, Crane CH, Koong AC, Das P, Wang X, Javle M, Krishnan S. Nab-Paclitaxel, Capecitabine, and Radiation Therapy After Induction Chemotherapy in Treating Patients With Locally Advanced and Borderline Resectable Pancreatic Cancer: Phase 1 Trial and Imaging-based Biomarker Validation. Int J Radiat Oncol Biol Phys. 2022 Nov 1;114(3):444-453. doi: 10.1016/j.ijrobp.2022.06.089. Epub 2022 Jul 18.

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