Clinical trial NCT04130399: Study of Neoadjuvent Chemotherapy Followed by SBRT in Patients With Resectable and Borderline Resectable Pancreatic Cancer
Official title: Study of Neoadjuvent Chemotherapy Followed by SBRT in Patients With Resectable and Borderline Resectable Pancreatic Cancer
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE2
Conditions: Pancreatic Cancer
Pancreatic Adenocarcinoma
Keywords: Folfirinox
Cancer
Radiation Therapy
neoadjuvent chemotherapy
Stereotactic Body Radiation Therapy (SBRT)
Lead sponsor: Indiana University
Sponsor class: OTHER
First posted: 2019-10-17
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: preoperative chemotherapy with FOLFIRINOX followed by SBRT in patients with resectable pancreatic cancer.
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to research the effects of delivering full-dose neoadjuvant multi-agent chemotherapy (folfirinox) followed by stereotactic body radiation therapy (SBRT) in patients with resectable pancreatic ductal adenocarcinoma (PDAC) in order to intensify local therapy and improve outcomes.

Detailed description: Primary Objectives:

1. To assess one-year local control rates in patients with operable PDAC who receive neoadjuvant chemotherapy and SBRT

Secondary Objectives:

1. To assess the following disease control endpoints: pathological response, disease-free survival, overall survival, failure pattern (local vs. distant) and time to development of distant metastases
2. To assess safety of the SBRT regimen

Exploratory objectives

1. To obtain exploratory data correlating tumor response grade with changes in circulating tumor DNA levels following chemotherapy, SBRT, and surgery in patients with PDAC
2. To obtain exploratory data correlating circulating tumor DNA (ctDNA) changes with disease control endpoints (overall survival, disease-free survival, failure pattern, and time to development of distant metastases)
3. To obtain exploratory data on positron emission tomography (PET) and magnetic resonance imaging (MRI) findings and correlations with tumor response among patients treated on study.

Eligibility criteria: Inclusion Criteria:

1. Age ≥ 18 years
2. Pathologic confirmation of pancreatic ductal adenocarcinoma
3. Resectable disease (determined by treating surgeon)
4. Patients planning to receive neoadjuvant Folfirinox as part of their standard of care treatment
5. No evidence of distant organ metastatic disease
6. Eastern Cooperative Oncology Group Performance status 0-1
7. Ability to understand and the willingness to sign informed consent document
8. Adequate organ function, defined by the following laboratory values, at the time of study entry:

   1. Hemoglobin ≥ 10 g/dL (transfusions acceptable)
   2. Absolute Neutrophil Count ≥ 0.5 x 109/L
   3. Platelets ≥ 100 x 109/L
   4. Creatinine ≤ 1.5x institutional upper limit of normal (ULN) or creatinine clearance ≥ 50 mL/min
   5. Total bilirubin ≤ 2x institutional ULN
   6. Aspartate aminotransferase test (AST)/ Alanine Aminotransferase Test (ALT) ≤ 3x institutional ULD

Exclusion Criteria:

1. Severe/uncontrolled intercurrent illness that, in the opinion of the patient's treating physicians, would prevent the patient from receiving either multi agent chemotherapy, high-dose radiation, or undergoing resection of the pancreatic tumor
2. Prior therapy for PDAC
3. Prior radiation to the upper abdomen (RT to other sites acceptable)
4. Inability to undergo port or PICC line placement
5. Active gastric or duodenal ulcer
6. Tumor invasion of the intestinal or gastric lumen
7. Active hepatitis B or other active serious infections
8. Pregnant and breastfeeding women are excluded. Women of child-bearing potential must have a negative urine or serum pregnancy test and be willing to use acceptable methods of birth control (hormonal or barrier method of birth control; abstinence) to avoid pregnancy for the duration of the study treatment
9. Life expectancy of \< 3 months
10. Patients with contraindications to either PET scan or MRI (e.g., pacemaker/ICD) will NOT be excluded from study participation. Such patients will be treated per protocol but will not be required to undergo PET-MRI.

Primary outcomes:
measure: Local control rate among PDAC patients treated with neoadjuvant chemotherapy followed by SBRT
timeFrame: 1 year after surgery date
Secondary outcomes:
measure: Pathological tumor response grade
timeFrame: Surgery Date (4 weeks [+/- 14 days] from end of SBRT)
measure: Rate of margin negative resection
timeFrame: Surgery Date (4 weeks [+/- 14 days] from end of SBRT)
measure: Rate of progression free survival
timeFrame: From surgery date to first documented date of progression, up to 5 years
measure: Overall survival
timeFrame: From surgery date to date of death, up to 5 years
measure: Local control rate
timeFrame: from date of surgery until date of first documented local failure, up to 5 years
measure: Time to development of distant metastases
timeFrame: From surgery date to date of first documented metastatic disease, up to 5 years
measure: Site of first failure
timeFrame: From surgery date to date of first documented metastatic disease, up to 5 years
measure: Rate of grade 3-4 non hematological toxicity rates
timeFrame: Date of first fraction of SBRT through 30 days (+/-14) after surgery date
Other outcomes:
Locations:
city: Indianapolis
country: United States
facility: Indiana University Melvin & Bren Simon Cancer Center
state: Indiana
Study officials:
affiliation: Indiana University School of Medicine
name: Susannah Ellsworth, MD
role: PRINCIPAL_INVESTIGATOR
References: