Study of Neoadjuvent Chemotherapy Followed by SBRT in Patients With Resectable and Borderline Resectable Pancreatic Cancer

Sponsor

Indiana University (Other)

Overall Status

Withdrawn

CT.gov ID

NCT04130399

Collaborator

(none)

Enrollment

Location

Arm

42.1

Anticipated Duration (Months)

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Pancreatic Cancer Pancreatic Adenocarcinoma	Radiation: Stereotactic Body Radiation Therapy (SBRT) Drug: FOLFIRINOX	Phase 2

Detailed Description

Primary Objectives:

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

Secondary Objectives:

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
To assess safety of the SBRT regimen

Exploratory objectives

To obtain exploratory data correlating tumor response grade with changes in circulating tumor DNA levels following chemotherapy, SBRT, and surgery in patients with PDAC
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)
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.

Study Design

Study Type:

Interventional

Actual Enrollment :

0 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Intervention Model Description:

preoperative chemotherapy with FOLFIRINOX followed by SBRT in patients with resectable pancreatic cancer.preoperative chemotherapy with FOLFIRINOX followed by SBRT in patients with resectable pancreatic cancer.

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Study of Neoadjuvent Chemotherapy Followed by SBRT in Patients With Resectable and Borderline Resectable Pancreatic Cancer

Anticipated Study Start Date :

Jul 1, 2019

Anticipated Primary Completion Date :

Jan 1, 2022

Anticipated Study Completion Date :

Jan 1, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Preoperative Chemotherapy + SBRT Participants in this trial will receive neoadjuvant and adjuvant FOLFIRINOX chemotherapy for 6 cycles (1 cycle = 14 days) per routine guidelines. After 6 cycles of neoadjuvant therapy are completed, patients will undergo imaging with pancreatic protocol CT and PET-MRI to assess disease status . Patients without evidence of disease progression at the end of 6 cycles of neoadjuvant treatment will proceed to SBRT followed by surgical resection. Following surgery, patients will receive an additional 6 cycles of FOLFIRINOX chemotherapy.	Radiation: Stereotactic Body Radiation Therapy (SBRT) Patients will receive 5 fractions of SBRT delivered over a five-day period. Treatment may be delivered over 2 weeks, provided that the patient receives at least 2 fractions per week. Drug: FOLFIRINOX Participants in this trial will receive neoadjuvant and adjuvant FOLFIRINOX chemotherapy for 6 cycles (1 cycle = 14 days) per routine guidelines

Arm

Intervention/Treatment

Experimental: Preoperative Chemotherapy + SBRT

Participants in this trial will receive neoadjuvant and adjuvant FOLFIRINOX chemotherapy for 6 cycles (1 cycle = 14 days) per routine guidelines. After 6 cycles of neoadjuvant therapy are completed, patients will undergo imaging with pancreatic protocol CT and PET-MRI to assess disease status . Patients without evidence of disease progression at the end of 6 cycles of neoadjuvant treatment will proceed to SBRT followed by surgical resection. Following surgery, patients will receive an additional 6 cycles of FOLFIRINOX chemotherapy.

Radiation: Stereotactic Body Radiation Therapy (SBRT)

Patients will receive 5 fractions of SBRT delivered over a five-day period. Treatment may be delivered over 2 weeks, provided that the patient receives at least 2 fractions per week.

Drug: FOLFIRINOX

Participants in this trial will receive neoadjuvant and adjuvant FOLFIRINOX chemotherapy for 6 cycles (1 cycle = 14 days) per routine guidelines

Outcome Measures

Primary Outcome Measures

Local control rate among PDAC patients treated with neoadjuvant chemotherapy followed by SBRT [1 year after surgery date]

Secondary Outcome Measures

Pathological tumor response grade [Surgery Date (4 weeks [+/- 14 days] from end of SBRT)]
Rate of margin negative resection [Surgery Date (4 weeks [+/- 14 days] from end of SBRT)]
Rate of progression free survival [From surgery date to first documented date of progression, up to 5 years]
Overall survival [From surgery date to date of death, up to 5 years]
Local control rate [from date of surgery until date of first documented local failure, up to 5 years]
Time to development of distant metastases [From surgery date to date of first documented metastatic disease, up to 5 years]
Site of first failure [From surgery date to date of first documented metastatic disease, up to 5 years]
Rate of grade 3-4 non hematological toxicity rates [Date of first fraction of SBRT through 30 days (+/-14) after surgery date]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Age ≥ 18 years
Pathologic confirmation of pancreatic ductal adenocarcinoma
Resectable disease (determined by treating surgeon)
Patients planning to receive neoadjuvant Folfirinox as part of their standard of care treatment
No evidence of distant organ metastatic disease
Eastern Cooperative Oncology Group Performance status 0-1
Ability to understand and the willingness to sign informed consent document
Adequate organ function, defined by the following laboratory values, at the time of study entry:
Hemoglobin ≥ 10 g/dL (transfusions acceptable)
Absolute Neutrophil Count ≥ 0.5 x 109/L
Platelets ≥ 100 x 109/L
Creatinine ≤ 1.5x institutional upper limit of normal (ULN) or creatinine clearance ≥ 50 mL/min
Total bilirubin ≤ 2x institutional ULN
Aspartate aminotransferase test (AST)/ Alanine Aminotransferase Test (ALT) ≤ 3x institutional ULD

Exclusion Criteria:

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
Prior therapy for PDAC
Prior radiation to the upper abdomen (RT to other sites acceptable)
Inability to undergo port or PICC line placement
Active gastric or duodenal ulcer
Tumor invasion of the intestinal or gastric lumen
Active hepatitis B or other active serious infections
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
Life expectancy of < 3 months
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.