A Dose Escalation Trial of SBRT After Induction Chemotherapy for Locally Advanced Pancreatic Cancer

This is a phase I study, with an expansion cohort, of up to 34 patients to identify the
maximum tolerated dose (MTD) of a 3-fraction regimen of stereotactic body radiotherapy (SBRT)
for locally-advanced pancreatic cancer patients who have not developed distant progression
following induction chemotherapy (FOLFIRINOX or gemcitabine and nab-paclitaxel) as per
standard of care. After completion of induction chemotherapy, stereotactic body radiotherapy
SBRT will be administered in 3 fractions, every other day, on an outpatient basis. Dose
escalation will start with dose level 1 (9 Gy x 3 fractions) and increase by 1 Gy per
fraction at each dose level, dose level 2 will be 10 Gy x 3 fractions and dose level 3 will
be 11 Gy x 3 fractions.

Inclusion Criteria:

1. Histologically or cytopathologically confirmed adenocarcinoma of the pancreas.

2. Locally advanced, unresectable pancreatic cancer as confirmed by the multidisciplinary
input from a hepatobiliary surgeon and as defined on CT as having tumor abutment of
>180° (> 50%) of the circumference of the superior mesenteric artery (SMA) or celiac
axis, unreconstructable superior mesenteric vein (SMV) or portal vein (PV)
involvement.

3. No evidence of distant metastasis either prior to or after induction chemotherapy.

4. 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.

5. Pancreatic tumor size ≤ 5 cm.

6. Age ≥18 years.

7. ECOG 0-1.

8. Patients must have acceptable organ and marrow function as defined below:

- Leukocytes >3,000/µL

- Absolute neutrophil count >1,500/µL

- Platelets >70,000/µL

- Total bilirubin Within 2 x upper limit of normal

- AST (SGOT)/ALT (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

9. Ability to understand and follow the breathing instructions involved in the
respiratory gating procedure or to tolerate compression sufficient to reduce fiducial
motion to <= 5mm.

10. Ability to understand and the willingness to sign a written informed consent document.

11. Residual or on-going ≥ Grade 3 treatment-related toxicity from previous chemotherapy

Exclusion Criteria:

1. Patients who have had prior abdominal radiotherapy.

2. Patients receiving any investigational agents.

3. 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.

4. Contraindication to IV contrast

5. Patients in which iodine contrast is contraindicated.

6. 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 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.