Clinical trial NCT02873598: A Dose Escalation Trial of SBRT After Induction Chemotherapy for Locally Advanced Pancreatic Cancer
Official title: A Dose Escalation Trial of Stereotactic Body Radiotherapy (SBRT) After Induction Chemotherapy for Locally Advanced Pancreatic Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Pancreatic Cancer
Keywords: Induction Chemotherapy
Stereotactic Body Radiotherapy (SBRT)
Dose Escalation
Locally Advanced Pancreatic Cancer (LAPC)
Maximum Tolerated Dose (MTD)
Lead sponsor: University of Colorado, Denver
Sponsor class: OTHER
First posted: 2016-08-19
Enrollment: 14
Sex: ALL
Minimum age (years): 18
Maximum age (years): 99
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
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.
Primary purpose: TREATMENT

Brief 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).

Detailed description: 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.

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.

Primary outcomes:
measure: The Maximum Tolerated Dose (MTD) of Stereotactic Body Radiotherapy (SBRT) in Locally Advanced Pancreatic Cancer (LAPC) Patients Who Have Not Developed Distant Progression After Induction Chemotherapies.
timeFrame: Up to 3 months
Secondary outcomes:
measure: Local Control
timeFrame: Up to 5 years
measure: Progression Free Survival
timeFrame: Up to 5 years
measure: Overall Survival
timeFrame: Up to 5 years
measure: Small Intestine Changes
timeFrame: 6 weeks after SBRT
measure: Vascular and Cellular Changes
timeFrame: 6 weeks after SBRT
measure: Quality of Life (QOL)
timeFrame: 6 months after SBRT
Other outcomes:
Locations:
city: Aurora
country: United States
facility: University of Colorado
state: Colorado
Study officials:
affiliation: University of Colorado, Denver
name: Sana Karam, MD
role: PRINCIPAL_INVESTIGATOR
References: