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FOLFIRINOX Regimen or Gemcitabine-Nab-paclitaxel Followed by Stereotactic Body Radiation Therapy in Treating Patients with Locally Advanced Inoperable or Borderline Inoperable Pancreatic Cancer

Trial Status: Active

This pilot clinical trial studies the side effects of fluorouracil, irinotecan hydrochloride, leucovorin calcium and oxaliplatin (FOLFIRINOX regimen) or gemcitabine-nab-paclitaxel followed by stereotactic body radiation therapy in treating patients with pancreatic cancer that has spread from its original site to nearby tissues or lymph nodes and cannot be removed by surgery, or is difficult to remove by surgery due to the tumor surrounding major blood channels in the pancreas. Drugs used in chemotherapy, such as the FOLFIRINOX regimen and gemcitabine-nab-paclitaxel, 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. Stereotactic body radiation therapy uses special equipment to position a patient and deliver radiation to tumors with high precision. This method can kill tumor cells with fewer doses over a shorter period and cause less damage to normal tissue. Giving the FOLFIRINOX regimen or gemcitabine-nab-paclitaxel followed by stereotactic body radiation therapy may work better in treating patients with pancreatic cancer.

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 version [v]1.1) on imaging studies CT
  • Karnofsky performance status greater than or equal to 70 or Eastern Cooperative Oncology Group (ECOG) performance of 0-2
  • Estimated life expectance > 12 weeks
  • If female patient is of child bearing potential, she must have a negative serum pregnancy test (beta hCG) documented up to 72 hours (hrs) prior to administration of first study drug
  • Absolute neutrophil count (ANC) > 1.5 x 10^9/L; should be drawn =< 14 days prior to enrollment
  • Platelet count >= 100000/mm^3; should be drawn =< 14 days prior to enrollment
  • Hemoglobin (HgB) >= 9 g/dL; should be drawn =< 14 days prior to enrollment
  • Aspartate aminotransferase (AST), alanine aminotransferase (ALT) =< 2.5 x upper limit of normal (ULN); should be drawn =< 14 days prior to enrollment
  • Total bilirubin =< 1.5 ULN; should be drawn =< 14 days prior to enrollment
  • Serum creatinine (Cr) within normal limits (WNL); should be drawn =< 14 days prior to enrollment
  • Prothrombin time and international normalized ratio (PT/INR) and partial thromboplastin time (PTT) within normal limits (+/- 15%); should be drawn =< 14 days prior to enrollment
  • 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
  • Patients with scleroderma, ulcerative colitis or other systemic conditions 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 human immunodeficiency virus (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
  • The patient must not be pregnant or breast-feeding at enrollment in the study; absence of pregnancy must be demonstrated by serum or urine testing prior to surgery for collection of study related tissue for patients of childbearing potential; female patients of child bearing potential (i.e., ovulating, premenopausal, not surgical sterile) must use a medically accepted contraceptive regimen while receiving neo-adjuvant chemotherapy; if a female patient becomes pregnant during the study, the subject must immediately notify their provider; pregnancies will be handled on a case-by-case basis; to ensure patient safety, each pregnancy occurring while the patient is on study treatment and for up to 12 months should be followed up to determine outcome, including spontaneous or voluntary termination, details of the birth, and the presence or absence of any birth defects, congenital abnormalities, or maternal and/or newborn complications

Alabama

Birmingham
University of Alabama at Birmingham Cancer Center
Status: ACTIVE
Contact: Ravi Kumar Paluri
Phone: 205-975-2477

PRIMARY OBJECTIVES:

I. To evaluate safety and tolerability associated with neoadjuvant chemotherapy followed by stereotactic body radiotherapy (SBRT) in locally advanced pancreatic cancer (LAPC).

SECONDARY OBJECTIVES:

I. To estimate progression-free survival (PFS) and overall survival (OS) for all patients.

II. To evaluate the rate of preoperative chemo radio therapy completion.

III. To estimate the proportion of patients undergoing surgery after preoperative chemoradiation therapy.

TERTIARY OBJECTIVES:

I. To evaluate tumor and circulating free deoxyribonucleic acid (DNA) for mutations relevant to pancreatic cancer.

II. Correlation of tumor response using dual energy computed tomography (CT) imaging with 1-year PFS and OS.

OUTLINE: Patients are assigned to 1 of 2 arms.

ARM 1: Patients receive oxaliplatin intravenously (IV) over 2 hours, leucovorin calcium IV over 90 minutes, irinotecan hydrochloride IV over 90 minutes days 1 and 15, and fluorouracil IV continuously over 46-48 hours on days 1-3 and 15-17. Treatment repeats every 4 weeks for up to 2 courses in the absence of disease progression or unacceptable toxicity. Within 4 weeks, patients with no evidence of metastatic disease at the completion of course 2 then undergo stereotactic body radiation therapy (SBRT) every other day (QOD) over 5 fractions.

ARM 2: Patients receive nab-paclitaxel IV over 30-40 minutes and gemcitabine IV over 30 minutes on days 1, 8, and 15. Treatment repeats every 4 weeks for up to 2 courses in the absence of disease progression or unacceptable toxicity. Within 4 weeks, patients with no evidence of metastatic disease at the completion of course 2 then undergo SBRT as in Arm 1.

After completion of study treatment, patients are followed up at 4 weeks and then every 3 months for 1 year.

Trial Phase Phase NA

Trial Type Treatment

Lead Organization
University of Alabama at Birmingham Cancer Center

Principal Investigator
Ravi Kumar Paluri

  • Primary ID UAB1632
  • Secondary IDs NCI-2017-01946
  • Clinicaltrials.gov ID NCT03600623