Neoadjuvant Folfirinox Followed by Capecitabine and Limited Field Radiation for Localized Pancreatic Head Adenocarcinoma

This study is currently recruiting participants.
Verified November 2013 by Medical University of South Carolina
Sponsor:
Information provided by (Responsible Party):
Melanie Thomas, Medical University of South Carolina
ClinicalTrials.gov Identifier:
NCT01677988
First received: August 29, 2012
Last updated: November 21, 2013
Last verified: November 2013
  Purpose

This study is for subjects with adenocarcinoma of the pancreas. The purpose of this research study is to determine the safety and effectiveness of Folfirinox and radiation therapy as treatment for adenocarcinoma (cancer) of the pancreas before surgery. Screening tests will be done to determine if subjects are eligible for participation in this study. If subjects are eligible to participate and agree to participate they will begin chemotherapy. After 3 cycles of chemotherapy, subjects will begin chemoradiation. Within 4 to 8 weeks of completing radiation therapy, subjects will have surgery. There will also be post-treatment and follow-up evaluations. Subjects will be followed for every 3 months for 3 years after their initial registration.


Condition Intervention Phase
Adenocarcinoma of Head of Pancreas
Drug: Neo-adjuvant Chemotherapy
Radiation: Chemoradiation
Procedure: Surgical Resection
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase II Study of Neoadjuvant Folfirinox Chemotherapy Followed by Capecitabine With Concurrent Limited Field Radiation Therapy in Patients With Localized Pancreatic Head Adenocarcinoma

Resource links provided by NLM:


Further study details as provided by Medical University of South Carolina:

Primary Outcome Measures:
  • Primary Objective [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
    We will estimate the R0/R1 resection rate as the proportion of patients with R0 or R1 resection status based on the ITT population. Any patient for whom a surgical sample is not available will be considered a failure (that is, such patients will be counted in the denominator of the estimated proportion, but will contribute a 0 to its numerator). We will also construct exact binomial 95% CIs to provide a measure of the estimated R0/R1 resection rate's precision.


Secondary Outcome Measures:
  • Secondary Outcome [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]

    Radiographic tumor response:

    The rate of CR, PR, SD and PD will be estimated as described in Section 14B prior to chemoradiation start and prior to surgery. The analysis population for estimation of radiographic response rate will be the ITT population. In addition, ORR (= CR + PR) will be estimated along with corresponding exact 95% CIs.


  • Secondary Outcome [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]

    Histopathologic tumor response:

    We will estimate the rate of good histopathologic response as the proportion of grade I and II responders. The analysis population for this objective is the ITT population. Any patient for whom a surgical sample is not available will be considered a poor-responder. We will also construct exact binomial 95% CIs to provide a measure of the estimated response rate's precision. We will also construct point and interval estimates of the rate of poor response. All pancreaticoduodenectomy specimens will be independently reviewed by both Dr. Lewin and Dr. Sun to assess histopathologic response. Should independent evaluations of response differ, Drs. Lewin and Sun will confer to arrive at a consensus evaluation.


  • Secondary Outcome [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]

    Time to recurrence:

    Time to recurrence will be assessed graphically, and the median TTR will be estimated based on the resulting Kaplan Meier curve. An exponential Greenwood 95% CI will be constructed corresponding to the median TTR. The analysis population for estimation of median TTR will be the surgical population (recurrence is defined only among those patients who are resected with curative intent). Additionally, we will estimate median TTR separately for subpopulations of surgical patients with R0 and R1 resection status.


  • Secondary Outcome [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]

    Overall survival:

    Median OS and corresponding 95% CI will be estimated as described in Section 14E. The analysis population for estimation of median OS will be the ITT population. As described in Section 7, all patients will be followed until death or three years after initial registration, whichever occurs first.



Other Outcome Measures:
  • Feasibility objective [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
    The feasibility of treating patients with localized pancreatic head adenocarcinoma with this neoadjuvant regimen will be evaluated by estimating the proportion of patients completing five of six planned doses. The analysis population will be the ITT population.

  • Exploratory objectives [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
    For each of the 42 sphingome genes, ΔCt will be measured in duplicate for each patient sample and averaged. For each gene, we will summarize central tendency and dispersion for patients with R0/R1 resection status and those patients not achieving R0/R1 resection status using descriptive measures including mean, median, SD, inter-quartile range and range. We will construct boxplots with overlayed jittered data points to graphically assess differences in gene expression. If the data are not too sparse, we will examine the predictive potential of sphingome genes by conducting simple logistic regressions of the log odds of R0/R1 resection on average ΔCt for each gene of interest, and estimate the area under the curve of the receiver operating characteristic curve.


Estimated Enrollment: 30
Study Start Date: July 2012
Estimated Study Completion Date: September 2014
Estimated Primary Completion Date: September 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Adjuvant Chemoradiation
Neo-adjuvant Chemotherapy- Modified FOLFIRINOX chemotherapy Day 1 and Day 15 of 28 day cycles for 3 cycles with growth factor support Chemoradiaton Surgical Resection
Drug: Neo-adjuvant Chemotherapy
  1. Modified FOLFIRINOX chemotherapy Day 1 and Day 15 of 28 day cycles, for three (3) cycles with growth factor support.
  2. Restaging # 1. (CT or MRI; use same modality as baseline staging unless otherwise indicated by Study Team)

    1. Progressive Disease (PD) → Off study. Subsequent treatment per patient's primary MD.
    2. Stable Disease (SD) or Tumor Response → Continue to Registration #2 for Chemoradiation.
Other Name: FOLFIRINOX chemotherapy
Radiation: Chemoradiation
  1. Chemoradiation may be administered at selected approved CTN sites.
  2. Determination of resectability as reviewed and documented by MUSC-HCC GI Tumor Board.

    1. Unresectable → Off study. Subsequent treatment per patient's primary MD.
    2. Resectable → Continue to Registration #3 for Surgical Resection
Procedure: Surgical Resection
  1. Meets criteria for resectable* →pancreaticoduodenectomy (POD)
  2. At time of resection, snap frozen tumor specimen sent for correlative biomarker studies

  Eligibility

Ages Eligible for Study:   18 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patient has histologically or cytologically confirmed borderline resectable adenocarcinoma of the pancreas. Patients with islet cell or other neuroendocrine neoplasms are excluded.
  • Borderline resectable disease2,22 as defined by:
  • Staging by intravenous contrast-enhanced thin section helical abdominal computed tomography (2.5 mm cuts or less) or MRI (for patients with an IV contrast allergy) using pancreatic protocol. Endoscopic ultrasound is required for tissue acquisition and staging confirmation:
  • AJCC stage III.
  • May have abutment of the superior mesenteric artery, (SMA),
  • abutment of the celiac axis;
  • May have abutment or short segment encasement of the common hepatic artery (CHA);
  • May have short segment occlusion of the SMA-PV confluence if reconstruction is possible.
  • No evidence of distant disease.
  • ≥ 18 years of age.
  • Male or non-pregnant and non-lactating female. If a female patient is of childbearing potential, she must have a negative serum pregnancy test (β hCG) documented within 72 hours of the first administration of study drug.
  • If sexually active, the patient must agree to use contraception considered adequate and appropriate by the Investigator.
  • Patient must not have received prior chemotherapy or radiation for pancreatic cancer and no exposure to systemic chemotherapy.
  • Patient has the following blood counts at baseline:
  • ANC ≥ 1.5 x 109/L (1500 /mm³)
  • Platelets ≥ 125 x 109/L (125,000/mm³)
  • Hgb ≥ 10 g/dL.
  • Patient has the following blood chemistry levels at baseline:
  • AST (SGOT), ALT (SGPT) ≤ 2.5 x upper limit of normal (ULN)
  • Alkaline phosphatase (AP) ≤ 2.5 X ULN
  • Total bilirubin ≤ 2.0mg/dl
  • Serum creatinine ≤1.5mg/dl or calculated clearance ≥ 50 mL/min/1.73 m² for patients with serum creatinine levels >1.5 mg/dl.
  • Albumin > 2.5 g/dL.
  • For patients not receiving anticoagulation: International Normalized Ratio of a measure of prothrombin time (INR) < 1.3.
  • Patient has an ECOG performance status PS 0-1.
  • Patient has been informed about the nature of the study and has agreed to participate in the study and signed the Informed Consent Form prior to participation in any study-related activities.
  • Endoscopic ultrasound (EUS) with FNA for cytology.
  • Patients should not have any evidence of active or uncontrolled infection requiring treatment with antibiotics.

Exclusion Criteria:

  • Patient has localized resectable, locally advanced unresectable or advanced metastatic disease. Patients with adenocarcinoma of the pancreatic body or tail are ineligible.
  • Patient has active, uncontrolled bacterial, viral, or fungal infection(s) requiring systemic therapy.
  • Patient has known infection with HIV.
  • Patient has undergone major surgery, other than diagnostic surgery (i.e.surgery done to obtain a biopsy for diagnosis without removal of an organ), within 4 weeks prior to Day 1 of treatment in this study.
  • Prior chemotherapy, immunotherapy or radiation for pancreatic cancer.
  • Patient has a history of allergy or hypersensitivity to the study drugs.
  • Patient has serious medical risk factors involving any of the major organ systems such that the Investigator considers it unsafe for the patient to receive chemotherapy and/or radiation therapy.
  • Patients must not require chronic use of immunosuppressive agents (e.g. methotrexate, cyclosporine).
  • No other prior malignancy is allowed except for the following: adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, adequately treated Stage I or II cancer from which the patient is currently in complete remission, or any other cancer from which the patient has been disease-free for five years.
  • Patients must not have clinically significant cardiovascular disease (including myocardial infarction, unstable angina, symptomatic congestive heart failure, serious uncontrolled cardiac arrhythmia) < 1 year before randomization.
  • Patients must not have a history of any medical or psychiatric condition or laboratory abnormality that in the opinion of the investigator may increase the risks associated with the study participation or investigational product(s) administration or may interfere with the interpretation of the results.
  • Patient is unwilling or unable to comply with study procedures.
  • Patient is enrolled in any other therapeutic clinical protocol or investigational trial.
  • Patients aged ≥ 80 are not excluded. However, candidates in this age group should be thoroughly evaluated before enrollment in the study, to ensure they are fit to receive chemotherapy, and to potentially undergo pancreaticoduodenectomy. In addition to meeting all of the baseline patient selection criteria, clinical judgment regarding the patient's susceptibility to infection, expected stability of their performance status, and suitability to receive intensive chemotherapy cycles should be paid special attention. Patients should not be enrolled in the study should there be any hesitation on any of these considerations. Baseline criteria for all patients enrolled on the study must be carefully evaluated and all criteria followed appropriately.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01677988

Contacts
Contact: Melanie Thomas, MD 843-792-5329 thomasmb@musc.edu
Contact: Andie Adelman 843-792-1507 adelman@musc.edu

Locations
United States, South Carolina
Medical University of South Carolina Recruiting
Charleston, South Carolina, United States, 29425
Contact: Melanie Thomas, MD    843-792-5329    thomasmb@musc.edu   
Contact: Andie Adelman    843-792-1507    adelman@musc.edu   
Principal Investigator: Melanie Thomas, MD         
Sponsors and Collaborators
Medical University of South Carolina
Investigators
Principal Investigator: Melanie Thomas, MD Medical University of South Carolina
  More Information

No publications provided

Responsible Party: Melanie Thomas, Associate Professor, Medical University of South Carolina
ClinicalTrials.gov Identifier: NCT01677988     History of Changes
Other Study ID Numbers: 101822
Study First Received: August 29, 2012
Last Updated: November 21, 2013
Health Authority: United States: Institutional Review Board

Keywords provided by Medical University of South Carolina:
NEOADJUVANT FOLFIRINOX CHEMOTHERAPY
LOCALIZED PANCREATIC HEAD ADENOCARCINOMA
RADIATION THERAPY

Additional relevant MeSH terms:
Adenocarcinoma
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Capecitabine
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on April 15, 2014