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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT03099265
Recruitment Status : Active, not recruiting
First Posted : April 4, 2017
Last Update Posted : July 20, 2021
Information provided by (Responsible Party):
Yale University

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.

Condition or disease Intervention/treatment Phase
Pancreatic Cancer Drug: neoadjuvant mFOLFIRINOX Drug: Stereotactic body radiotherapy (SBRT) Phase 2

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 9 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase II Study to Evaluate Neoadjuvant Modified FOLFIRINOX and Stereotactic Body Radiation Therapy in Borderline Resectable Pancreatic Adenocarcinoma
Actual Study Start Date : June 26, 2017
Estimated Primary Completion Date : February 2022
Estimated Study Completion Date : August 2022

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
Experimental: 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.
Drug: 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.
Other Names:
  • Oxaliplatin
  • Irinotecan
  • Leucovorin
  • 5-fluorouracil
  • folinic acid

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.

Primary Outcome Measures :
  1. R0 resection rate [ Time Frame: Up to 40 weeks ]
    The primary outcome of this study is the R0 resection rate in patients with BRPC treated with neoadjuvant mFOLFIRINOX and SBRT. R0 resection indicates a microscopically margin-negative resection, in which no gross or microscopic tumor remains in the primary tumor bed.

Secondary Outcome Measures :
  1. Radiographic response to neoadjuvant therapy [ Time Frame: Up to 40 weeks ]
    Response to treatment will be assessed by the treating physicians and investigators according to RECIST version 1.1

  2. Pathologic response to neoadjuvant therapy [ Time Frame: Up to 40 weeks ]
    A pathologic complete response is defined as the absence of residual invasive disease at the completion of the neoadjuvant treatment.

  3. Rates of recurrence [ Time Frame: Up to 40 weeks ]
    Local only, systemic only, and local or systemic rates of recurrence

  4. Progression free survival [ Time Frame: Up to 5 years ]
    Estimated using Kaplan-Meier analysis

  5. Overall survival [ Time Frame: Up to 5 years ]
    Estimated using Kaplan-Meier analysis

  6. Grade 3 or greater acute and late gastrointestinal toxicity [ Time Frame: Up to 40 weeks ]
    To determine rates of grade 3 or greater gastrointestinal toxicity, including acute toxicities occurring within 3 months of treatment, and late toxicities occurring over 3 months after completion of radiation.

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT03099265

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United States, Connecticut
Smilow Cancer Hospital
New Haven, Connecticut, United States, 06510
Sponsors and Collaborators
Yale University
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Principal Investigator: Kimberly Johung, MD, PhD Yale University
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Responsible Party: Yale University Identifier: NCT03099265    
Other Study ID Numbers: 2000020432
First Posted: April 4, 2017    Key Record Dates
Last Update Posted: July 20, 2021
Last Verified: July 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: Yes
Additional relevant MeSH terms:
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Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Molecular Mechanisms of Pharmacological Action
Antimetabolites, Antineoplastic
Antineoplastic Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Topoisomerase I Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Protective Agents
Vitamin B Complex