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Combination Chemotherapy and Stereotactic Body Radiation Therapy in Treating Patients with Resectable Pancreatic Adenocarcinoma

Trial Status: Temporarily Closed to Accrual

This phase II trial studies how well combination chemotherapy and stereotactic body radiation therapy work in treating patients with pancreatic cancer that can be removed by surgery. Drugs used in chemotherapy, such as fluorouracil, irinotecan hydrochloride, leucovorin calcium and oxaliplatin, 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 combination chemotherapy followed by stereotactic body radiation therapy may work better in treating patients with pancreatic cancer.

Inclusion Criteria

  • Histologically confirmed pancreatic adenocarcinoma
  • Borderline resectable pancreatic adenocarcinoma, determined centrally by review of a diagnostic CT scan and/or magnetic resonance imaging (MRI) scan with contrast by a dedicated surgical oncologist and radiologist, or as determined by EUS, and defined according to one of the following four National Comprehensive Cancer Network (NCCN) consensus guidelines: * Tumors of the pancreatic head or uncinate process with: ** Solid tumor contact with the common hepatic artery (CHA) without extension to the celiac axis (CA) or hepatic artery bifurcation allowing for safe and complete resection and reconstruction, or ** Solid tumor contact with the superior mesenteric artery (SMA) of =< 180 degrees, or ** Presence of variant arterial anatomy such that the degree of tumor contact affects surgical planning * Tumors of the pancreatic body or tail with: ** Solid tumor contact with the CA of =< 180 degrees, or ** Solid tumor contact with the CA of > 180 degrees without involvement of the aorta and with intact and uninvolved gastroduodenal artery * Solid tumor contact with the superior mesenteric vein (SMV) or portal vein (PV) of >180 degrees, or contact of =< 180 degrees with contour irregularity of the vein or thrombosis of the vein but with suitable vessel proximal and distal to the site of involvement allowing for safe and complete resection and vein reconstruction * Solid tumor contact with the inferior vena cava (IVC)
  • No evidence of extrapancreatic disease on diagnostic imaging (CT, MRI, or positron emission tomography [PET] scan), or laparoscopy, including nodal involvement beyond the peri-pancreatic tissues and/or distant metastases
  • No evidence of invasion into the duodenum or stomach, as determined by esophagogastroduodenoscopy (EGD)/EUS
  • No prior treatment (chemotherapy, biological therapy, or radiotherapy) for pancreatic cancer
  • No prior treatment with oxaliplatin, irinotecan, fluorouracil or capecitabine
  • Patients who received chemotherapy > 5 years ago for malignancies other than pancreatic cancer are eligible
  • No major surgery within 4 weeks of study entry
  • No other concurrent anticancer therapy
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0-1
  • No other malignancy within past five years (exceptions include basal cell carcinoma of the skin, cervical carcinoma in situ, and nonmetastatic prostate cancer)
  • No evidence of second malignancy at the time of study entry
  • No interstitial pneumonia or extensive and symptomatic interstitial fibrosis of the lung
  • No >= grade 2 sensory peripheral neuropathy
  • No uncontrolled seizure disorder, active neurological disease, or known central nervous system (CNS) disease
  • No significant cardiac disease, including the following: unstable angina, New York Heart Association class II-IV congestive heart failure, myocardial infarction within six months prior to study enrollment
  • Not pregnant and not nursing
  • No other medical condition or reason that, in the opinion of the investigator, would preclude study participation
  • Absolute neutrophil count >= 1,500/uL
  • Platelet count >= 75,000/uL
  • Hemoglobin >= 9 g/dL
  • Creatinine < 1.5 x upper limit of normal (ULN) or estimated glomerular filtration rate (GFR) > 30 ml/min
  • Bilirubin < 1.5 x ULN
  • Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) < 3 x ULN
  • Negative pregnancy test in women of childbearing potential
  • Able to be treated with SBRT only at the Smilow New Haven campus
  • Able to have fiducials placed in the pancreas

Connecticut

New Haven
Yale University
Status: TEMPORARILY_CLOSED_TO_ACCRUAL
Contact: Kimberly Lauren Johung
Phone: 203-737-6876

PRIMARY OBJECTIVES:

I. To evaluate the residual tumor (R0) resection rate after neoadjuvant modified fluorouracil, irinotecan hydrochloride, leucovorin calcium and oxaliplatin (FOLFIRINOX) and subsequent stereotactic body radiation therapy (SBRT) for borderline resectable pancreatic cancer.

SECONDARY OBJECTIVES:

I. To evaluate the radiographic response to neoadjuvant therapy by comparing intravenous (IV) contrast computed tomography (CT) scans before and after therapy.

II. To evaluate the pathologic response to neoadjuvant chemotherapy and stereotactic radiation.

III. To determine rates of recurrence (local only, systemic only, and both local and systemic), progression free survival, and overall survival.

IV. To determine rates of grade 3 or greater gastrointestinal toxicity, including acute toxicities occurring within 3 months of treatment, and late toxicities occurring over 3 months after completion of radiation.

EXPLORATORY OBJECTIVES:

I. To prospectively assess quantitative KRAS mutation-associated circulating tumor deoxyribonucleic acid (DNA) as a predictive marker of response to neoadjuvant therapy or a prognostic marker of outcomes.

II. To evaluate endoscopic ultrasound elastography measurements of tumor stiffness (change in strain ratio between the normal and tumor region before and after chemotherapy) as a predictor of outcomes.

III. To correlate response of CA19-9 to pre-operative therapy with outcomes.

IV. To collect and bank serial serum and plasma specimens from subjects for future correlative biomarker studies.

V. To collect and bank tumor tissue from subjects prior to treatment (at the time of diagnostic endoscopic ultrasound [EUS]), after treatment with pre-operative FOLFIRINOX (at the time of fiducial placement for SBRT), and after SBRT (from the surgical specimen) for future correlative biomarker studies

OUTLINE:

Patients receive mFOLFIRINOX consisting of oxaliplatin IV over 2 hours, leucovorin calcium or levoleucovorin IV over 2 hours, irinotecan IV over 90 minutes, and fluorouracil IV continuous over 46 hours on day 1. Courses repeat every 14 days for up to 8 courses in the absence of disease progression or unacceptable toxicity. Patients without progression receive 5 fractions of stereotactic body radiation therapy over 2 weeks and undergo surgical resection within 4-12 weeks of completing SBRT. Within 12 weeks after surgery, patients receive mFOLFIRINOX for an additional 4 courses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 30 days, every 3 months for 3 years, every 6 months for 2 years, and then annually thereafter.

Trial Phase Phase II

Trial Type Treatment

Lead Organization
Yale University

Principal Investigator
Kimberly Lauren Johung

  • Primary ID 2000020432
  • Secondary IDs NCI-2018-02169
  • Clinicaltrials.gov ID NCT03099265