Stereotactic Body Radiation Therapy after Induction Chemotherapy in Treating Patients with Locally Advanced Pancreatic Cancer

Status: Active

Description

This phase I trial studies the side effects of stereotactic body radiation therapy after induction chemotherapy in treating patients with pancreatic cancer that has spread from where it started to nearby tissue or lymph nodes. 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 chemotherapy before radiation therapy may kill more tumor cells.

Eligibility Criteria

Inclusion Criteria

  • Histologically or cytopathologically confirmed adenocarcinoma of the pancreas
  • Locally advanced, unresectable pancreatic cancer as confirmed by the multidisciplinary input from a hepatobiliary surgeon and as defined on computed tomography (CT) as having tumor abutment of > 180 degrees (> 50%) of the circumference of the superior mesenteric artery (SMA) or celiac axis, unreconstructable superior mesenteric vein (SMV) or portal vein (PV) involvement
  • No evidence of distant metastasis either prior to or after induction chemotherapy
  • Completion of at least 3 months, but no more than 6 months of standard induction chemotherapy for LAPC, which may include FOLFIRINOX or gemcitabine and nab-paclitaxel, preferably within 2-4 weeks but no longer than 8 weeks
  • Pancreatic tumor size =< 5 cm
  • Eastern Cooperative Oncology Group (ECOG) 0-1
  • Leukocytes > 3,000/uL
  • Absolute neutrophil count > 1,500/uL
  • Platelets > 50,000/uL
  • Total bilirubin within 2 x upper limit of normal
  • Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamic pyruvic 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
  • Ability to understand and follow the breathing instructions involved in the respiratory gating procedure or to tolerate compression sufficient to reduce fiducial motion to =< 5 mm
  • Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria

  • Patients who have had prior abdominal radiotherapy
  • Patients receiving any other investigational agents
  • Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
  • Contraindication to magnetic resonance imaging
  • Patients in which 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 urine or 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 identify the maximum tolerated dose (MTD) of stereotactic body radiotherapy (stereotactic body radiation therapy [SBRT]) in locally advanced pancreatic cancer (LAPC) patients who have not developed distant progression after following induction chemotherapy (leucovorin calcium, fluorouracil, irinotecan hydrochloride, and oxaliplatin [FOLFIRINOX] or gemcitabine [gemcitabine hydrochloride] and nab-paclitaxel [paclitaxel albumin-stabilized nanoparticle formulation] as per standard of care).

SECONDARY OBJECTIVES:

I. To preliminarily assess the 2 year local control, progression free and overall survival rates for LAPC patients after induction chemotherapy and SBRT. Patterns of failure will also be investigated.

II. To identify early changes in the normal small intestine after SBRT for LAPC using diffusion weighted imaging (DWI)-magnetic resonance imaging (MRI) and dynamic contrast-enhanced (DCE)-MRI derived parameters to document changes in tissue perfusion kinetics and heterogeneity that predict for development of gastrointestinal toxicity such as duodenal ulcers, strictures, or enteritis. This is only for cohorts 1-3.

III. To investigate vascular and cellular changes resulting from SBRT for LAPC using DWI-MRI and DCE-MRI derived parameters that can predict treatment response and to assess any correlation between these DWI-MRI and DCE-MRI derived parameters and local control and progression-free survival. This is only for cohorts 1-3.

IV. Evaluate quality of life (QOL) in terms of global QOL, physical symptoms, physical functioning and emotional well-being after induction chemotherapy and SBRT.

V. To prospectively evaluate the feasibility of obtaining adequate cytology samples for next generation sequencing. This is only for cohorts 1-3.

OUTLINE: This is a dose-escalation study of SBRT.

Beginning at least 2-4 weeks after completion of standard care induction chemotherapy comprising FOLFIRINOX or gemcitabine hydrochloride and paclitaxel albumin-stabilized nanoparticle formulation, patients undergo a total of 3-15 fractions of SBRT administered every other day in the absence of disease progression or unacceptable toxicity. Patients also undergo DWI-MRI and DCE-MRI at baseline, within 90 minutes of the first fraction of SBRT, and at 6 weeks post-SBRT.

After completion of study treatment, patients are followed up at 6 weeks, 10-12 weeks, 6 months, 9 months, 12 months, and then every 6 months for 2-5 years.

Trial Phase & Type

Trial Phase

Phase I

Trial Type

Treatment

Lead Organization

Lead Organization
Memorial Sloan Kettering Cancer Center

Principal Investigator
Marsha Reyngold

Trial IDs

Primary ID 15-109
Secondary IDs NCI-2016-00285
Clinicaltrials.gov ID NCT02643498