Folfirinox or Gemcitabine-Nab Paclitaxel Followed by Stereotactic Body Radiotherapy for Locally Advanced Pancreatic Cancer

Neoadjuvant Folfirinox or Gemcitabine-Nab Paclitaxel Followed by Stereotactic Body Radiotherapy (SBRT) for Patients With Locally Advanced Pancreatic Cancer

This study will implement a new treatment regimen for patients with advanced and inoperable pancreatic cancer using chemotherapy combinations of Folfirinox or gemcitabine-nab paclitaxel (abraxane) followed by a short course of high dose radiation called Stereotactic Body Radiation Therapy (SBRT). While the chemotherapy is standard of care, the strategy of adding SBRT has not been investigated. An increase in the percentage of patients who can proceed to have surgery to remove their disease is anticipated with this approach.

Study Overview

• Status: Terminated
• Conditions: Pancreatic Cancer; Locally Advanced Pancreatic Cancer; Borderline Pancreatic Inoperable Cancer
• Intervention / Treatment: Drug: Folfirinox; Drug: Gemcitabine nab-Paclitaxel

Detailed Description

This pilot study will evaluate safety and tolerability of neoadjuvant chemotherapy followed by SBRT. Patients with locally advanced pancreatic cancer (LAPC) and borderline pancreatic inoperable cancer will be assigned to one of two treatment arms based upon performance status and physician's discretion. The two treatment arms are: Folfirinox or gemcitabine-nab paclitaxel (abraxane). There are no study drugs as all treatments are based on standard clinical pathways.

After two cycles of treatment patients will be restaged with CT scans or imaging. If the tumor remains resectable, borderline, or unresectable without progression of disease, then the patient will proceed to SBRT.

Follow-up visits will continue every three months for up to one year or until progression of disease.

• Study Type: Interventional
• Enrollment (Actual): 25
• Phase: Early Phase 1

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35294
      • University of Alabama at Birmingham

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Histologically or cytologically proven adenocarcinoma of the pancreas. Patients with mixed tumor with predominant adenocarcinoma pathology can be enrolled.
• Subjects will be staged according to the 2010 American Joint Committee on Cancer (AJCC) staging system with pathologic stage T1-4, being eligible; and have a primary tumor of the pancreas (either pancreatic head, neck, uncinate process, or body/tail)
• The tumor must be deemed as being borderline/unresectable. Final CT confirmation of surgical staging/ eligibility will be at the discretion of the pancreatic surgeon of the patient.
• Disease must be confined to loco-regional site as confirmed by CT imaging and/or diagnostic staging laparoscopy to avoid occult peritoneal deposits. Diagnostic laparoscopy will be performed only if absolutely required
• Measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST v1.1) on imaging studies CT
• Karnofsky performance status greater than or equal to 70 or Eastern Cooperative Oncology Group (ECOG) performance of 0-2.
• Age >18
• Estimated life expectance >12 weeks
• If female patient is of child bearing potential, she must have a negative serum pregnancy test (βhCG) documented up to 72 hrs prior to administration of first study drug
• Patient has screening blood work performed which includes the following (should be drawn ≤14 days prior to enrollment)
• Absolute neutrophil count (ANC) >1.5 x 109/L
• Platelet count ≥100,000/mm3
• Hemoglobin (Hgb) ≥ 9g/dL
• Aspartate aminotransferase (AST), Alanine Aminotransferase (ALT) ≤ 2.5 x upper limit of normal (ULN) Total Bilirubin ≤1.5 ULN
• Serum Cr within normal limits (WNL)
• Prothrombin Time and International Normalized Ratio (PT/INR) and Partial Thromboplastin Time (PTT) within normal limits (±15%).
• Disease must be encompassed in a reasonable SBRT "portal" as defined by the treating radiation oncologist

Exclusion Criteria:

• Ineligible Histology including non-adenocarcinomas, adenosquamous carcinoma, islet cell carcinomas, cystadenomas, cystadenocarcinomas, carcinoid tumors, duodenal carcinomas, distal bile duct and ampullary carcinomas
• Patients must not have received prior pancreatic surgery, radiation therapy, chemotherapy or any investigational therapy for pancreatic cancer.
• Patients with tumors extending or invading duodenum or gastric are not eligible.
• Evidence of distant metastasis on upright chest x-ray, CT or other staging studies
• Subjects with recurrent disease are not eligible
• Prior radiation therapy to the upper abdomen or liver at the discretion of the treating radiation oncologist could impair delivery of the prescribed radiation treatment
• Patients with scleroderma, ulcerative colitis or other systemic conditions deemed risky for radiation treatment. Therefore, will be excluded.
• Prior chemotherapy
• Subjects in their reproductive age who are breast feeding or have a positive pregnancy test
• Any co-morbid condition such as but not limited to congestive heart failure, cardiac arrhythmia or psychiatric illness of sufficient severity to limit full compliance with the protocol per assessment by the individual treating physician
• Concurrent active infection
• No prior malignancy allowed except cervical cancer in situ, adequately treated basal cell or squamous cell carcinoma of skin or treated low risk prostate cancer
• Patient with known historical or active infection with HIV, Hepatitis B or Hepatitis C
• Patient who has undergone recent major surgery, other than diagnostic surgical procedure within 4 weeks prior to enrollment.
• Patient who has a history of allergy or hypersensitivity to any of the study drugs.
• Patients with a history of interstitial lung disease, history of slowly progressive dyspnea and unproductive cough, sarcoidosis, silicosis, interstitial pulmonary fibrosis, pulmonary hypersensitivity pneumonitis or multiple allergies
• Patients with greater than grade 2 peripheral neuropathy at the time of enrollment are not eligible.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Folfirinox + SBRT; Folfirinox comprises the following: Fluorouracil 2,400 mg/m2 intravenously over 48 hours Days 1-3 and 15-17 every 4 weeks; Folinic acid 400 mg intravenously on Days 1 and 15 every 4 weeks; Oxaliplatin 85 mg/m2 intravenously on Days 1 and 15 every 4 weeks; and Irinotecan 180 mg/m2 intravenously on Days 1 and 15 every 4 weeks. Radiation will begin at the completion of cycle 2 if chemotherapy toxicity permits and will last over a period of 5 days.	Drug: Folfirinox; SBRT will follow Folfirinox at the completion of Cycle 2 (if eligible).; Other Names: Folfirinox = Fluorouracil + Folinic Acid + Oxaliplatin + Irinotecan
Experimental: Gemcitabine-nab Paclitaxel + SBRT; Gemcitabine-nab Paclitaxel comprises the following: Gemcitabine 1000 mg/m2 on Days 1, 8, and 15 every 4 weeks; nab Paclitaxel 125 mg/m2 on Days 1, 8, and 15 every 4 weeks. Radiation will begin at the completion of cycle 2 if chemotherapy toxicity permits and will last over a period of 5 days.	Drug: Gemcitabine nab-Paclitaxel; SBRT will follow Gemcitabine nab-Paclitaxel at the completion of Cycle 2 (if eligible).; Other Names: Paclitaxel = Abraxane

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of participants with adverse events as a measure of safety and tolerability	Initial dose of drug until 4 weeks following completion of therapy which may or may not include SBRT and follow-up. Adverse event reporting will be graded following the National Cancer Institute of Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.0.	Baseline up to two years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-free survival	Progression-free survival is the duration of time from study entry to time of disease progression or death, whichever comes first.	Baseline up to two years
Overall survival	Overall survival is the duration of time from study entry to time of death or the date of last contact.	Baseline to two years
Rate of preoperative chemotherapy + radiotherapy completion	The rate will be determined from the measurement of lesions (maximum of 2 per organ with no more than 5 lesions total) from CT scans and magnetic resonance imaging within the study time frame.	Baseline to two years
Proportion of participants undergoing surgery after preoperative chemoradiation therapy	Comparison of participants who underwent surgery versus those that did not following preoperative chemoradiation therapy	Baseline to two years

Collaborators and Investigators

• Sponsor: University of Alabama at Birmingham
• Investigators: Principal Investigator: Ravi K Paluri, MD, University of Alabama at Birmingham

Study record dates

Study Major Dates

• Study Start (Actual): September 25, 2017
• Primary Completion (Actual): July 30, 2020
• Study Completion (Actual): July 31, 2020

Study Registration Dates

• First Submitted: July 17, 2018
• First Submitted That Met QC Criteria: July 17, 2018
• First Posted (Actual): July 26, 2018

Study Record Updates

• Last Update Posted (Actual): August 18, 2020
• Last Update Submitted That Met QC Criteria: August 14, 2020
• Last Verified: August 1, 2020

More Information

Terms related to this study

• Keywords: advanced pancreatic cancer; Stereotactic Body Radiotherapy; Folfirinox; inoperable pancreatic cancer; Gemcitabine-Abraxane; Gemcitabine-nab-Paclitaxel
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Endocrine System Diseases; Digestive System Neoplasms; Endocrine Gland Neoplasms; Pancreatic Diseases; Pancreatic Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Topoisomerase Inhibitors; Topoisomerase I Inhibitors; Gemcitabine; Paclitaxel; Fluorouracil; Oxaliplatin; Irinotecan; Albumin-Bound Paclitaxel; Folfirinox
• Other Study ID Numbers: IRB160830003 (UAB 1632)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No