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

Phase 2

Withdrawn

• Conditions: Pancreatic Cancer; Pancreatic Adenocarcinoma
• Interventions: Radiation: Stereotactic Body Radiation Therapy (SBRT); Drug: FOLFIRINOX

• Registration Number: NCT04130399
• Lead Sponsor: Indiana University

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.

Basic Information
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Recruitment & Eligibility
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Study & Design
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Trial Locations

Study Timeline

• Study Start: 2019-07-01
• Status Verified: 2019-09
• Study First Submitted: 2019-10-15
• Study First Submitted QC: 2019-10-15
• Last Update Submitted: 2019-10-15
• Study First Posted: 2019-10-17
• Last Update Posted: 2019-10-17
• Primary Completion: 2022-01-01
• Study Completion: 2023-01-01

Recruitment & Eligibility

• Status: WITHDRAWN
• Sex: All
• Target Recruitment: Not specified

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

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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.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Preoperative Chemotherapy + SBRT	FOLFIRINOX	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.
Preoperative Chemotherapy + SBRT	Stereotactic Body Radiation Therapy (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.

Primary Outcome Measures

Name	Time	Method
Local control rate among PDAC patients treated with neoadjuvant chemotherapy followed by SBRT	1 year after surgery date

Secondary Outcome Measures

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

Trial Locations

Locations (1)

Indiana University Melvin & Bren Simon Cancer Center; 🇺🇸 Indianapolis, Indiana, United States