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Borderline Pancreas Study: FOLFIRINOX +SBRT (GCC 1324)

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ClinicalTrials.gov Identifier: NCT01992705
Recruitment Status : Completed
First Posted : November 25, 2013
Last Update Posted : August 19, 2019
Sponsor:
Information provided by (Responsible Party):
Department of Radiation Oncology, University of Maryland, Baltimore

Tracking Information
First Submitted Date  ICMJE September 27, 2013
First Posted Date  ICMJE November 25, 2013
Last Update Posted Date August 19, 2019
Study Start Date  ICMJE March 2014
Actual Primary Completion Date September 27, 2018   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: November 19, 2013)
Rate of downstaging to resectability in patients with borderline resectable pancreatic cancer receiving FOLFIRINOX and SBRT as preoperative therapy. [ Time Frame: Participants will be followed from randomization up to 120 months or death (from any cause) whichever comes first. ]
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).
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT01992705 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: November 19, 2013)
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 [ Time Frame: Participants will be followed from randomization up to 120 months or death (from any cause) whichever comes first. ]
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)
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures
 (submitted: November 19, 2013)
  • Number of adverse events/toxicites reported during and following treatment of FOLFIRINOX and SBRT in patients with resectable pancreatic cancer [ Time Frame: Participants will be followed from randomization up to 120 months or death (from any cause) whichever comes first. ]
    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).
  • Radiologic and pathological response associated with preoperative SBRT and FOLFIRINOX therapy [ Time Frame: Participants will be followed from randomization up to 120 months or death (from any cause) whichever comes first. ]
    To determine the radiologic and pathological response associated with preoperative SBRT and FOLFIRINOX therapy (review of radiology and pathology reports).
  • Quality of life through and after treatment [ Time Frame: Participants will be followed from randomization up to 120 months or death (from any cause) whichever comes first. ]
    To assess quality of life through and after treatment using the FACT-Hep questionnaire
Original Other Pre-specified Outcome Measures Same as current
 
Descriptive Information
Brief Title  ICMJE Borderline Pancreas Study: FOLFIRINOX +SBRT
Official Title  ICMJE Neoadjuvant FOLFIRINOX and Stereotactic Body Radiotherapy (SBRT) Followed by Definitive Surgery for Patients With Borderline Resectable Pancreatic Adenocarcinoma: A Single-Arm Pilot Study
Brief Summary

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
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  ICMJE Interventional
Study Phase  ICMJE Early Phase 1
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Resectable Pancreatic Cancer
Intervention  ICMJE
  • 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.
Study Arms  ICMJE 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

Interventions:
  • 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
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: February 26, 2019)
8
Original Estimated Enrollment  ICMJE
 (submitted: November 19, 2013)
20
Actual Study Completion Date  ICMJE September 27, 2018
Actual Primary Completion Date September 27, 2018   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01992705
Other Study ID Numbers  ICMJE HP-00055716
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Department of Radiation Oncology, University of Maryland, Baltimore
Study Sponsor  ICMJE University of Maryland, Baltimore
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Shahed Badiyan, MD University of Maryland, College Park
PRS Account University of Maryland, Baltimore
Verification Date August 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP