Borderline Pancreas Study: FOLFIRINOX +SBRT (GCC 1324)

Neoadjuvant FOLFIRINOX and Stereotactic Body Radiotherapy (SBRT) Followed by Definitive Surgery for Patients With Borderline Resectable Pancreatic Adenocarcinoma: A Single-Arm Pilot Study

Primary Objective: To determine the rate of downstaging to resectability in patients with borderline resectable pancreatic cancer receiving FOLFIRINOX and SBRT as preoperative therapy.

Secondary Objective(s):

1. To assess the disease-free-survival, overall survival, time to recurrence and site of recurrence in patients with borderline resectable pancreatic cancer receiving preoperative FOLFIRINOX followed by SBRT
2. To investigate the safety and tolerability of FOLFIRINOX and SBRT in patients with resectable pancreatic cancer
3. To determine the radiologic and pathological response associated with preoperative SBRT and FOLFIRINOX therapy
4. To assess quality of life through and after treatment using the FACT-Hep questionnaire

Study Overview

• Status: Completed
• Conditions: Resectable Pancreatic Cancer
• Intervention / Treatment: Other: Chemotherapy(FOLFIRINOX) + SBRT prior to surgery if applicable; Drug: -Oxaliplatin 85 mg/m2 IV on Day 1; Drug: -Irinotecan 180 mg/m2 IV on Day 1; Drug: -5-FU (Fluorouracil) 2,400 mg/m2 IV over 46-48 hours

Detailed Description

The study investigators hypothesize that neoadjuvant FOLFIRINOX can be safely and efficaciously delivered using a sequential regimen with SBRT as an alternative to standard neoadjuvant chemoradiotherapy. Standard of care neoadjuvant treatment typically requires about six weeks of treatment with sub-systemic dosing of chemotherapy. The feasibility of the sequential delivery of the FOLFIRINOX followed by SBRT will be evaluated by capturing the prevalence of grade 3 toxicity and the treatment delay rate.

In our study, SBRT is planned sequentially to follow cycle 4 of chemotherapy treatment, provided toxicity has resolved to grade 2 or less. Thus, allowing for resolution of chemotherapy toxicity prior to initiation of radiation therapy. This interval and the fact that there is no concurrent delivery of chemo-RT, based on previously discussed experiences, including approaches where SBRT safely follows other intense chemotherapy regimens (see Polistina et al and Chuong [35,36]) makes this study feasible without establishing toxicity profile.

The proposed regimen of 4 cycles of FOLFIRINOX followed by 30 Gy/5 fractions using SBRT will be safely tolerated and will improve resectability rates in borderline resectable PDAC patients. In addition, this regimen will not compromise the ability to achieve a successful Whipple resection.

This regimen will improve the local control rate and overall disease free survival in this patient population. The investigators further hypothesize that early administration of FOLFIRNOX will provide optimal systemic therapy to control clinically occult micrometastases.

• Study Type: Interventional
• Enrollment (Actual): 8
• Phase: Early Phase 1

Contacts and Locations

Study Locations

• United States
  • Maryland
    • Baltimore, Maryland, United States, 21201
      • University of Maryland Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• ≥ 18 years at diagnosis.
• Biopsy proven pancreatic adenocarcinoma.
• Borderline resectable per NCCN criteria (No distant metastases, venous involvement of the portal vein/SMV, demonstrating tumor abutment and narrowing of the lumen, encasement of the portal vein/SMV without encasement of the nearby arteries, or short-segment venous occlusion resulting from either tumor thrombus or encasement but with suitable vessel proximal or distal to this area of vessel involvement, allowing for safe resection and reconstruction; gastroduodenal artery encasement up to the hepatic artery with either short segment encasement or direct abutment of the hepatic artery, without extension to the celiac axis; tumor abutment of the SMA not to exceed 180 degrees of the circumference of the vessel wall.).
• Radiologically measurable or clinically evaluable disease.
• Pancreas protocol CT and/or MRI if required for further clarification of disease tissue planes within 4 weeks of registration.
• ECOG PS of 0-2.
• Able to get a Whipple resection per surgeon assessment performed within 4 weeks of registration.
• The following laboratory values obtained ≤ 28 days prior to registration:
• Absolute neutrophil count (ANC) ≥ 1,500/mm3.
• Platelet count ≥ 100,000/mm3.
• Hemoglobin > 8.0 g/dL.
• Total bilirubin ≤ 1.5 x upper limit of normal (ULN).
• SGOT (AST) ≤ 2 x ULN.
• SGPT (ALT) ≤ 2 x ULN.
• Creatinine ≤ 1.5 x ULN.
• CA 19-9 level (to establish baseline).
• A negative pregnancy test within 7 days prior to registration for women of childbearing potential. In addition, male and female participants must commit to adequate contraception while on study.
• Able to provide written informed consent.
• Willing to return for all required study assessments.
• Neurological assessment for pre-existing peripheral neuropathy.
• Documentation of pre-existing hearing deficits.

Exclusion Criteria:

• Any pancreatic adenocarcinoma that does not meet criteria for borderline resectable disease.
• Prior history of abdominal radiation therapy.
• History of autoimmune disease such as scleroderma, lupus, and inflammatory bowel disease.
• Patients with tumor-caused symptomatic bowel obstruction.
• Chemotherapy (including hormonal therapy) within the past 5 years from date of registration.
• Other invasive malignancies within the past 5 years from date of registration.
• Pregnant or nursing women or women of childbearing age that are unwilling to employ adequate contraception.
• Other co-morbid conditions which, based on the judgment of the physicians obtaining informed consent, would make the patient inappropriate for this study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Other: Chemotherapy+SBRT prior to surgery if applicable; FOLFIRINOX Drugs: Calcium Folinate (Folinic Acid) 400 mg IV on Day 1 of each cycle (21d/cycle for a total of 4 cycles. Stereotactic Body Radiotherapy (SBRT): 30 Gy in 5 fractions given to radiographically defined pancreatic mass alone

Other: Chemotherapy(FOLFIRINOX) + SBRT prior to surgery if applicable; Patients will receive chemotherapy (21d/cycle for a total of 4 cycles) plus SBRT before screening for surgical resection of the pancreas.; Drug: -Oxaliplatin 85 mg/m2 IV on Day 1; Oxaliplatin 85 mg/m2 IV on Day 1 of each cycle (21d/cycle for a total of 4 cycles).; Drug: -Irinotecan 180 mg/m2 IV on Day 1; Irinotecan 180 mg/m2 IV on Day 1 of each cycle (21d/cycle for a total of 4 cycles).; Drug: -5-FU (Fluorouracil) 2,400 mg/m2 IV over 46-48 hours; 5-FU (Fluorouracil) 2,400 mg/m2 IV over 46-48 hours of each cycle (21d/cycle for a total of 4 cycles.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rate of downstaging to resectability in patients with borderline resectable pancreatic cancer receiving FOLFIRINOX and SBRT as preoperative therapy.	To determine the rate of downstaging to resectability in patients with borderline resectable pancreatic cancer receiving FOLFIRINOX and SBRT as preoperative therapy (AGGC 6th edition).	Participants will be followed from randomization up to 120 months or death (from any cause) whichever comes first.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Survival status (disease-free-survival vs. overall survival) time to recurrence and site of recurrence in patients with borderline resectable pancreatic cancer receiving preoperative FOLFIRINOX followed by SBRT	To assess the disease-free-survival, overall survival, time to recurrence and site of recurrence in patients with borderline resectable pancreatic cancer receiving preoperative FOLFIRINOX followed by SBRT (RECIST)	Participants will be followed from randomization up to 120 months or death (from any cause) whichever comes first.

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of adverse events/toxicites reported during and following treatment of FOLFIRINOX and SBRT in patients with resectable pancreatic cancer	Number of toxicities participants reported by participants during and following treatment with FOLFIRINOX and SBRT in patients with resectable pancreatic cancer (NIH CTCAE v.4).	Participants will be followed from randomization up to 120 months or death (from any cause) whichever comes first.
Radiologic and pathological response associated with preoperative SBRT and FOLFIRINOX therapy	To determine the radiologic and pathological response associated with preoperative SBRT and FOLFIRINOX therapy (review of radiology and pathology reports).	Participants will be followed from randomization up to 120 months or death (from any cause) whichever comes first.
Quality of life through and after treatment	To assess quality of life through and after treatment using the FACT-Hep questionnaire	Participants will be followed from randomization up to 120 months or death (from any cause) whichever comes first.

Collaborators and Investigators

• Sponsor: University of Maryland, Baltimore
• Investigators: Principal Investigator: Shahed Badiyan, MD, University of Maryland, College Park

Study record dates

Study Major Dates

• Study Start: March 1, 2014
• Primary Completion (Actual): September 27, 2018
• Study Completion (Actual): September 27, 2018

Study Registration Dates

• First Submitted: September 27, 2013
• First Submitted That Met QC Criteria: November 19, 2013
• First Posted (Estimate): November 25, 2013

Study Record Updates

• Last Update Posted (Actual): August 19, 2019
• Last Update Submitted That Met QC Criteria: August 15, 2019
• Last Verified: August 1, 2019

More Information

Terms related to this study

• Keywords: pancreatic cancer
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Endocrine System Diseases; Digestive System Neoplasms; Endocrine Gland Neoplasms; Pancreatic Diseases; Pancreatic Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Topoisomerase Inhibitors; Topoisomerase I Inhibitors; Fluorouracil; Oxaliplatin; Irinotecan; Folfirinox
• Other Study ID Numbers: HP-00055716