Neoadjuvant Modified FOLFIRINOX and Stereotactic Body Radiation Therapy in Borderline Resectable Pancreatic Adenocarcinoma

NCT ID: NCT03099265

Last Updated: 2022-10-27

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 9 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-06-26
• Study Completion Date: 2019-09-18

Brief Summary

Surgical resection is the only potentially curative treatment for patients with pancreatic cancer. Patients with BRPC have tumors in close contact with the vasculature but not to the extent that resection is prohibited. Nonetheless, retrospective studies have shown that immediate resection in these patients is associated with an increased risk of positive margins, and a margin positive resection does not improve survival over that of patients with unresectable disease. Moreover, even in those patients where a successful resection is achieved, there is a high rate of early metastatic progression suggesting that micrometastatic disease is often present at diagnosis. Therefore neoadjuvant therapy is likely to improve outcomes in patients with BRPC to increase the likelihood of achieving a margin negative resection, provide early control of occult micrometastatic disease, and select those patients without systemic progression who would benefit from surgical resection.

Detailed Description

Given the superior outcomes with FOLFIRINOX and the potential for improved local response with SBRT, the investigators propose to evaluate the efficacy of pre-operative modified FOLFIRINOX followed by SBRT in patients with borderline resectable pancreatic adenocarcinoma. The investigators hypothesize that pre-operative modified FOLFIRINOX followed by SBRT will improve the rate of R0 resections compared to historical controls treated with standard gemcitabine-based chemotherapy and fractionated radiation prior to surgery.

Conditions

Pancreatic Cancer

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

patients with borderline resectable pancreatic adenocarcinoma

Borderline resectable disease will be defined by NCCN criteria, and determined centrally by review of a diagnostic pancreas protocol CT scan and/or MRI scan with contrast by a dedicated surgical oncologist and radiologist.

Group Type: EXPERIMENTAL

neoadjuvant mFOLFIRINOX

Intervention Type: DRUG

Patients will receive 8 cycles of mFOLFIRINOX every 2 weeks. mFOLFIRINOX will be dosed as follows: Oxaliplatin 85 mg/m2, followed by folinic acid 400 mg/m2 infused over 120 minutes and irinotecan 135 mg/m2 infused over 90 minutes, followed by 5-fluorouracil 300 mg/m2 IV bolus, followed by 2,400 mg/m2 continuous infusion for 46 hours. Levoleucovorin may be substituted for folinic acid at a dose of 200 mg/m2 infused over 120 minutes.

Stereotactic body radiotherapy (SBRT)

Intervention Type: DRUG

Stereotactic body radiotherapy (SBRT) will be delivered to the primary tumor and any adjacent involved nodes to 33 Gy in 5 fractions over the course of 2 weeks, and within 4 weeks of chemotherapy.

Interventions

neoadjuvant mFOLFIRINOX

Patients will receive 8 cycles of mFOLFIRINOX every 2 weeks. mFOLFIRINOX will be dosed as follows: Oxaliplatin 85 mg/m2, followed by folinic acid 400 mg/m2 infused over 120 minutes and irinotecan 135 mg/m2 infused over 90 minutes, followed by 5-fluorouracil 300 mg/m2 IV bolus, followed by 2,400 mg/m2 continuous infusion for 46 hours. Levoleucovorin may be substituted for folinic acid at a dose of 200 mg/m2 infused over 120 minutes.

Intervention Type: DRUG

Stereotactic body radiotherapy (SBRT)

Stereotactic body radiotherapy (SBRT) will be delivered to the primary tumor and any adjacent involved nodes to 33 Gy in 5 fractions over the course of 2 weeks, and within 4 weeks of chemotherapy.

Intervention Type: DRUG

Other Intervention Names

Oxaliplatin; Irinotecan; Leucovorin; 5-fluorouracil; folinic acid

Eligibility Criteria

Inclusion Criteria

• Histologically confirmed pancreatic adenocarcinoma
• Borderline resectable pancreatic adenocarcinoma, determined centrally by review of a diagnostic CT scan and/or MRI scan with contrast by a dedicated surgical oncologist and radiologist, or as determined by EUS, and defined according to the NCCN consensus guidelines
• ECOG Performance Status of 0-1
• Age > 18
• Laboratory parameters as follows:

• Absolute neutrophil count >=1,500/uL
• Platelet count >=100,000/uL
• Hemoglobin >=9 g/dL
• Creatinine <1.5 X ULN or estimated GFR >30 ml/min
• Bilirubin =<1.5 X ULN
• AST and ALT =<3 X ULN
• Negative pregnancy test in women of childbearing potential
• Able to have fiducials placed in the pancreas
• Patients who received chemotherapy >5 years ago for malignancies other than pancreatic cancer are eligible

Exclusion Criteria

• Evidence of extrapancreatic disease on diagnostic imaging (CT, MRI, or PET scan), or laparoscopy, including nodal involvement beyond the peripancreatic tissues and/or distant metastases
• Evidence of invasion into the duodenum or stomach, as determined by EGD/EUS
• Prior treatment (chemotherapy, biological therapy, or radiotherapy) for pancreatic cancer
• Prior treatment with oxaliplatin, irinotecan, fluoruouracil or capecitabine
• Major surgery within 4 weeks of study entry
• Other concurrent anticancer therapies
• Other malignancy within the past five years (exceptions include basal cell carcinoma of the skin, cervical carcinoma in situ, and non-metastatic prostate cancer)
• Evidence of second malignancy at the time of study entry
• Interstitial pneumonia or extensive and symptomatic interstitial fibrosis of the lung
• Grade 2 or greater sensory peripheral neuropathy
• Uncontrolled seizure disorder, active neurological disease, or known CNS disease
• Significant cardiac disease, including the following: unstable angina, New York Heart Association class II-IV congestive heart failure, myocardial infarction within six months prior to study enrollment
• Pregnant or nursing
• Other medical condition or reason that, in the opinion of the investigator, would preclude study participation

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Yale University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Kimberly Johung, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Yale University

Locations

Smilow Cancer Hospital

New Haven, Connecticut, United States

Countries

United States

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

2000020432

Identifier Type: -

Identifier Source: org_study_id