A Dose Escalation Trial of SBRT After Induction Chemotherapy for Locally Advanced Pancreatic Cancer
Condition: Pancreatic Cancer
MeSH terms: Pancreatic Neoplasms
Intervention: FOLFIRINOX or gemcitabine/abraxane; SBRT
Intervention description: Patients will have received induction chemotherapy for 3+ months with either FOLFIRINOX or gemcitabine/abraxane with at least stable disease.; After completion of induction chemotherapy, stereotactic body radiation therapy (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.
Intervention MeSH terms: Paclitaxel; Gemcitabine; Albumin-Bound Paclitaxel; Folfirinox
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Sequential Assignment
Intervention model description: 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.
Masking: None (Open Label)
Enrollment: 14.0
Sex: All
Minimum age: 18 Years
Maximum age: 99 Years
Healthy volunteers: No
Keywords: Induction Chemotherapy; Stereotactic Body Radiotherapy (SBRT); Dose Escalation; Locally Advanced Pancreatic Cancer (LAPC); Maximum Tolerated Dose (MTD)

Summary:

      This is a dose escalation trial to evaluate the safety of stereotactic body radiotherapy
      (SBRT) delivered in 3 fractions for patients with locally advanced pancreatic cancer (LAPC)
      who have received induction chemotherapy (FOLFIRINOX or gemcitabine and nab-paclitaxel).
    

Eligibility criteria:

        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.