Hypofractionated Ablative Intensity-Modulated Radiation Therapy and Capecitabine or Fluorouracil in Treating Patients with Potentially Resectable Locally Advanced Pancreatic Cancer

Status: Active

Description

This phase II trial studies how well hypofractionated ablative intensity-modulated radiation therapy and capecitabine or fluorouracil work in treating patients with pancreatic cancer that has spread from its original site of growth to nearby tissues or lymph nodes and may be able to be removed by surgery. Hypofractionated radiation therapy delivers higher doses of radiation therapy over a shorter period of time and may kill more tumor cells and have fewer side effects. Drugs used in chemotherapy, such as capecitabine and fluorouracil, 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. Giving hypofractionated ablative intensity-modulated radiation therapy and capecitabine or fluorouracil may work better in treating patients with pancreatic cancer.

Eligibility Criteria

Inclusion Criteria

  • Histologically or cytopathologically confirmed adenocarcinoma of the pancreas
  • Locally advanced, unresectable pancreatic cancer defined on post-induction chemotherapy computed tomography (CT) as having tumor involvement of > 180 degrees (> 50%) of the circumference of the superior mesenteric artery (SMA) or celiac axis, unreconstructable superior mesenteric vein (SMV) or pemphigus vulgaris (PV) involvement
  • No evidence of distant metastasis either prior to or after induction chemotherapy
  • Completion of at least 3 months of standard induction chemotherapy for locally advanced pancreatic carcinoma (LAPC), which may include fluorouracil/irinotecan/leucovorin calcium/oxaliplatin (FOLFIRINOX) or gemcitabine and nab-paclitaxel, within 6 weeks of enrollment
  • For patients currently receiving investigational agents, a washout of at least 2 weeks or 5 half-lives of experimental agent are required prior to the start of radiation therapy (RT)
  • Karnofsky performance status (KPS) 70-100
  • Leukocytes > 3,000/uL
  • Absolute neutrophil count > 1,500/uL
  • Platelets > 75,000/uL
  • Total bilirubin within 2 x upper limit of normal
  • Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) < 2.5 x institutional upper limit of normal
  • Creatinine within 1.5 x upper limit of normal, OR creatinine clearance > 60 mL/min for patients with creatinine levels above institutional normal
  • Any systemic therapy associated gastrointestinal (GI) toxicity should be grade 1 or less
  • Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria

  • Patients who have borderline resectable disease using National Comprehensive Cancer Network (NCCN) definition
  • Patients who have had prior abdominal radiotherapy
  • Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, or cardiac arrhythmia
  • Patients who are not surgical candidates due to medical co-morbidities
  • Patients in whom iodine contrast is contraindicated
  • Pregnant and breastfeeding women are excluded. Women of child-bearing potential who are unwilling or unable to use an acceptable method of birth control to avoid pregnancy for the entire study period and for up to 4 weeks after the study are excluded. This applies to any woman who has experienced menarche and who has not undergone successful surgical sterilization or is not postmenopausal defined as amenorrhea for at least 12 consecutive months, or women on hormone replacement therapy with serum follicle stimulating hormone (FSH) levels greater than 35 mIU/mL. A negative serum pregnancy test must be obtained within 14 days prior to the start of study therapy in all women of child-bearing potential. Male subjects must also agree to use effective contraception for the same period as above

Locations & Contacts

New Jersey

Basking Ridge
Memorial Sloan Kettering Basking Ridge
Status: Active
Contact: Marsha Reyngold
Phone: 631-623-4267
Middletown
Memorial Sloan Kettering Monmouth
Status: Active
Contact: Marsha Reyngold
Phone: 631-623-4267
Montvale
Memorial Sloan Kettering Bergen
Status: Active
Contact: Marsha Reyngold
Phone: 631-623-4267

New York

Commack
Memorial Sloan Kettering Commack
Status: Active
Contact: Marsha Reyngold
Phone: 631-623-4267
New York
Memorial Sloan Kettering Cancer Center
Status: Active
Contact: Marsha Reyngold
Phone: 631-623-4267
Uniondale
Memorial Sloan Kettering Nassau
Status: Active
Contact: Marsha Reyngold
Phone: 631-623-4267
West Harrison
Memorial Sloan Kettering Westchester
Status: Active
Contact: Marsha Reyngold
Phone: 631-623-4267

Trial Objectives and Outline

PRIMARY OBJECTIVES:

I. To assess the efficacy of hypofractionated ablative intensity-modulated radiation therapy (HFA-IMRT) in increasing the rate of conversion to resectability of patients with locally unresectable LAPC due to vessel encasement.

II. To evaluate 2 year overall survival.

SECONDARY OBJECTIVES:

I. To assess the safety of performing a surgical resection after high dose HFA-IMRT.

II. To evaluate local progression rate.

III. To evaluate 2-year progression-free survival and patterns of failure.

EXPLORATORY OBJECTIVES:

I. To explore cell free deoxyribonucleic acid (cfDNA) as a biomarker of response to HFA-IMRT.

OUTLINE:

Patients undergo HFA-IMRT over 20-40 minutes on Monday through Friday over 3-6 consecutive weeks. Patients also receive capecitabine orally (PO) twice daily (BID) on the days of radiation therapy or fluorouracil intravenously (IV) continuously 7 days per week at the discretion of the treating physician.

After completion of study treatment, patients are followed up at 1-1.5, 3, 6, 12, 18, and 24 months.

Trial Phase & Type

Trial Phase

Phase II

Trial Type

Treatment

Lead Organization

Lead Organization
Memorial Sloan Kettering Cancer Center

Principal Investigator
Marsha Reyngold

Trial IDs

Primary ID 18-090
Secondary IDs NCI-2018-01146
Clinicaltrials.gov ID NCT03523312