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Tumor Subtypes in Subjects on FOLFIRINOX With Non-Metastatic Pancreatic Cancer

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. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT03977233
Recruitment Status : Recruiting
First Posted : June 6, 2019
Last Update Posted : May 26, 2020
Information provided by (Responsible Party):
UNC Lineberger Comprehensive Cancer Center

Brief Summary:

This is a research study to evaluate how the genetic makeup of Pancreatic Ductal Adenocarcinoma (PDAC) can affect the response to FDA-approved chemotherapy treatment, FOLFIRINOX, given before surgery to remove the tumor. Certain types of PDAC tumors can be surgically resected (removed). However, not all types of PDACs are resectable, especially if they are close to important structures like blood vessels or intestines. These types of PDACs are treated with chemotherapy such as FOLFIRINOX. Research studies showed that chemotherapy after surgical resection of PDAC tumors reduced the risk of the cancer returning.

Chemotherapy is used to treat PDAC that has not spread outside of the pancreas and is not resectable. FOLFIRINOX is a chemotherapy treatment that combines multiple chemotherapeutic agents, including oxaliplatin, leucovorin, irinotecan, and 5-FU. Patients receive these agents by intravenous infusion. Of these drugs, 5-FU requires you to return home with a chemotherapy pump that will deliver chemotherapy over 46 hours. This regimen has been studied in pancreatic cancer that has been removed with surgery as a method for preventing the cancer from returning. Studies showed FOLFIRINOX chemotherapy reduced the risk of cancer returning and increased patients survival. In this study, researchers want to know if FOLFIRINOX chemotherapy given before surgery will make the cancer easier to remove with surgery and increase the chances of the cancer staying away after surgery.

Researchers have shown that pancreatic cancers are not all the same when you look at the DNA and RNA that is inside a pancreatic cancer cell.

Depending on the expression of different genes in a cancer cell, some pancreatic cancers may respond differently to chemotherapy. In this study researchers want to know if FOLFIRINOX chemotherapy can change the genetic profile of the cancer. This will be studied by obtaining a biopsy of the cancer before the start of chemotherapy, and after 8 treatments of chemotherapy. They will also study cancer cells that will be collected from blood samples.

Condition or disease Intervention/treatment Phase
Pancreatic Ductal Adenocarcinoma (PDAC) Cancer of Pancreas Pancreatic Cancer, Adult Pancreas Adenocarcinoma Pancreatic Neoplasms Pancreatic Cancer Non-resectable Pancreatic Cancer Resectable Drug: Oxaliplatin Drug: Leucovorin Drug: Irinotecan Hydrochloride Drug: 5-FU Phase 2

Detailed Description:

This is a single arm, phase II clinical trial designed to assess the impact of tumor and stromal molecular subtypes on the efficacy of neoadjuvant FOLFIRNOX in untreated subjects with resectable, borderline resectable and unresectable locally advanced pancreatic ductal adenocarcinoma (PDAC). Subjects will undergo an EUS-guided core biopsy of the pancreas prior to treatment and after cycle 8 of FOLFIRINOX. Imaging will be performed after every 4 cycles of chemotherapy (8 weeks) and reassessed for resectability after 12 cycles. If patients show a response to treatment that is deemed by the surgical oncologist to be amenable to resection, surgery can be pursued after 8 cycles of therapy. In this case, the remaining 4 cycles of treatment will be given after surgery.

Duration of Therapy:

In the absence of treatment delays due to adverse events, treatment may continue until:

  • Disease progression,
  • Inter-current illness that prevents further administration of treatment,
  • Unacceptable adverse event(s),
  • Subject decides to withdraw from the study, or
  • General or specific changes in the subject's condition render the subject unacceptable for further treatment in the judgment of the investigator.

Duration of Follow Up:

- Subjects will be followed for 36 months after removal from study treatment or until death, whichever occurs first. Subjects removed from study treatment for unacceptable adverse events will be followed until resolution or stabilization of the adverse event.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 45 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Impact of Tumor and Stromal Subtypes on Efficacy of Neoadjuvant FOLFIRINOX in Subjects With Non-Metastatic Pancreatic Cancer
Actual Study Start Date : June 12, 2019
Estimated Primary Completion Date : December 2022
Estimated Study Completion Date : December 2025

Resource links provided by the National Library of Medicine

Drug Information available for: Leucovorin

Arm Intervention/treatment
Experimental: SingleArm: FOLFIRINOX
Subjects will receive FOLFIRINOX as an outpatient every 14 days per community standards of medical care. Protocol-based therapy will continue for 12 cycles (24 weeks) or until disease progression, unacceptable toxicity, study withdrawal, or subject death. Subjects will have the option of surgical resection after 8 cycles of therapy if repeat scans show evidence of resectable disease. The starting doses for mFOLFIRINOX regimen are: oxaliplatin 85 mg/m2, followed by leucovorin 400 mg/m2 given simultaneously with irinotecan 180mg/m2, followed by 5FU 400 mg/m2 bolus and then 2400 mg/m2 via continuous infusion.
Drug: Oxaliplatin
85 mg/m2 in 250 cc Dextrose solution given by IV on Day 1 of each 14-day cycle
Other Name: Eloxatin

Drug: Leucovorin
400 mg/m2 in 100 cc dextrose solution given with irinotecan by IV on Day 1 of each 14-day cycle
Other Name: folinic acid

Drug: Irinotecan Hydrochloride
180 mg/m2 in 500cc dextrose solution given with leucovorin by IV on Day 1 of each 14-day cycle
Other Name: Camptosar

Drug: 5-FU
400 mg/m2 bolus and then 2400 mg/m2 via continuous infusion on Day 1 of each 14-day cycle
Other Name: Adrucil

Primary Outcome Measures :
  1. Best disease control rate by Pancreatic ductal adenocarcinoma (PDAC) subtype [ Time Frame: 6 months after start of treatment ]
    To evaluate the association between PDAC tumor subtype (particularly basal-like versus classical subtype) and best disease control rate (DCR) after administration of FOLFIRINOX in subjects with non-metastatic pancreatic cancer, DCR is defined as the proportion of patients with either Complete Response (CR), partial response (PR), or stable disease (SD) as determined by RECIST 1.1, Response Evaluation Criteria In Solid Tumors Criteria. CR is defined as disappearance of all target lesions; PR as a >=30% decrease in the sum of the longest diameter of target lesions; and SD as no response or less response than Partial or Progressive.

Secondary Outcome Measures :
  1. Rate of resectability [ Time Frame: 6 months after the start of treatment ]
    The number of patients who following treatment with FOLFIRINOX were subsequently deemed to have resectable disease and underwent surgical resection

  2. Overall survival [ Time Frame: 3 years ]
    median overall survival (OS) of all patients receiving FOLFIRINOX on study as well as in 1) resectable, 2) borderline resectable and 3) unresectable PDAC, measured from the start of treatment until death from any cause.

  3. Progression free survival [ Time Frame: 3 years ]
    Median time from start of treatment until death or progression as defined by RECIST 1.1 Criteria, for all patients and with respect to each tumor and stroma subtype. Progressive Disease (PD), is defined as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.

  4. best objective response rate (ORR; complete response (CR) + partial response (PR)) [ Time Frame: 6 months from start of study treatment ]
    Estimation of the best ORR for all patients and with respect to each tumor and stroma subtype. ORR is defined as the proportion of patients with either Complete Response (CR) or partial response (PR) as determined by RECIST 1.1, Response Evaluation Criteria In Solid Tumors Criteria. CR is defined as disappearance of all target lesions; PR as a >=30% decrease in the sum of the longest diameter of target lesions;

  5. rate of drug-related grade 3 to 5 adverse events [ Time Frame: 6 months from the start of treatment ]
    rate of drug-related grade 3 to 5 adverse events, assessed based upon patient reported toxicity as measured by the NCI Common Terminology Criteria for Adverse Events (CTCAE v5.0). The CTCAE is a descriptive terminology which can be utilized for Adverse Event (AE) reporting. A grading (severity) scale is provided for each AE term. Grade 1 Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated. Grade 2 Moderate; minimal, local or noninvasive intervention indicated; limiting age-appropriate instrumental Activities of Daily Living (ADL). Grade 3 Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self care ADL. Grade 4 Life-threatening consequences; urgent intervention indicated. Grade 5 Death related to AE.

  6. R0 resection rate [ Time Frame: 6 months from start of treatment ]
    The number of patients who underwent surgical resection and whose surgical specimens had a microscopically margin-negative resection (R0).

  7. proportion of patients whose tumor/stroma subtype changes after treatment with FOLFIRINOX [ Time Frame: 6 months from start of treatment ]
    The proportion of patients whose tumor/stroma subtype changed from baseline after treatment with FOLFIRINOX. This will be calculated separately for tumor and stroma.

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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Ages Eligible for Study:   18 Years to 99 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Written informed consent obtained to participate in the study and HIPAA authorization for release of personal health information.
  • Histologically or cytologically confirmed adenocarcinoma of the pancreas with no evidence of distant metastatic disease.
  • Subject has no evidence of co-morbidities precluding the potential to undergo surgical resection of PDAC as determined by surgical investigator.
  • Subjects must be willing to undergo a mandatory pre- and post-treatment EUS guided core biopsy of the pancreatic mass.
  • Measurable or non-measurable but evaluable (as determined by Response Evaluation Criteria in Solid Tumors version 1.1 [RECIST 1.1]) resectable, borderline resectable or unresectable locally advanced PDAC.
  • Subject has adequate performance status as defined by ECOG performance status 0 or 1.
  • Subject has received no prior chemotherapy or chemoradiotherapy for pancreatic cancer. Subjects have not previously received surgery to remove pancreatic cancer.
  • Age ≥ 18 years of age.
  • Subject has adequate organ function at study entry, as demonstrated by:

    • Hemoglobin ≥ 9 g/dL
    • ANC ≥ 1.5 × 109/L
    • Platelets ≥ 100 × 109/L
    • Creatinine ≤ 1.5 × ULN, or creatinine clearance ≥ 50 mL/min (as measured according to Cockcroft-Gault equation)
    • Total bilirubin ≤ 1.5 × ULN
    • AST/ALT ≤ 3 × ULN
    • GGT ≤ 5 × ULN.
  • Subject has life expectancy of at least 6 months.
  • Female subjects of childbearing potential must have a negative serum or urine pregnancy test performed within 14 days prior to initiation of FOLFIRINOX.
  • Female subjects of childbearing potential and male subjects must agree to use adequate contraception prior to study entry, for the duration of study participation, and 8 weeks after the end of treatment.

Exclusion Criteria:

  • Subject has any evidence of local recurrence or metastatic pancreatic cancer.
  • Other malignancies within the past 5 years except for adequately treated cervical or vulvar carcinoma in situ, treated basal cell carcinoma, superficial bladder tumors (Ta, Tis and T1).
  • Subject has hypersensitivity to 5FU, oxaliplatin or other platinum agent, or irinotecan or to their excipients.
  • Subject has known dihydropyrimidine dehydrogenase (DPD) enzyme deficiency.
  • Participation in any investigational drug study within 4 weeks preceding the start of study treatment. Subjects are not permitted to participate in another investigational drug study while being treated on this protocol.
  • Subject has current evidence of any condition that makes participating in this study not in the best interest of the subject, including but not limited to:

    • Myocardial infarction within the past 6 months
    • New York Heart Association (NYHA) Class III or IV heart disease
    • Active infection requiring IV antibiotics
  • Subject has a history of or suspected Gilbert's syndrome or known homozygosity for UGT1A1*28 polymorphism (baseline testing not required).
  • Subject has sensory peripheral neuropathy grade ≥ 2.
  • Major surgery, open biopsy or significant traumatic injury within 4 weeks of first study drug.
  • Subject is unable or unwilling to discontinue use of ketoconazole or St John's wort. Use of phenytoin, carbamazepine, phenobarbital, rifampin and rifabutin is discouraged, but not contraindicated. If subjects require phenytoin, carbamazepine or phenobarbital monitoring of drug levels is suggested during the study.
  • Subject is pregnant or lactating.
  • Psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule; those conditions should be discussed with the subject before registration in the trial.

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): NCT03977233

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Contact: Catherine Griffin, BS, BA 919-966-4432
Contact: Brian Burgess, BS 919-966-4432

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United States, North Carolina
University of North Carolina at Chapel Hill Lineberger Comprehensive Cancer Center Recruiting
Chapel Hill, North Carolina, United States, 27599
Contact: Autumn McRee, MD    919-966-5902   
Principal Investigator: Autumn McRee, MD         
Principal Investigator: Jen Jen Yeh, MD         
Sub-Investigator: Hanna Sanoff, MD, PhD         
Sub-Investigator: Michael S. Lee, MD         
Sub-Investigator: Cheryl Carlson, MD, PhD         
Sub-Investigator: Tammy Triglianos, RN, NP         
Sub-Investigator: Ugwuji Maduekwe, MD         
Sub-Investigator: Hong Jin Kim, MD         
Sub-Investigator: Todd Baron, MD         
Sponsors and Collaborators
UNC Lineberger Comprehensive Cancer Center
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Principal Investigator: Autumn McRee, MD University of North Carolina, Chapel Hill
Additional Information:
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Responsible Party: UNC Lineberger Comprehensive Cancer Center Identifier: NCT03977233    
Other Study ID Numbers: LCCC1843
First Posted: June 6, 2019    Key Record Dates
Last Update Posted: May 26, 2020
Last Verified: May 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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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.: No
Keywords provided by UNC Lineberger Comprehensive Cancer Center:
Pancreatic Ductal Adenocarcinoma
Pancreatic Cancer Non-resectable
Pancreatic Cancer Resectable
neoadjuvant FOLFIRNOX
Pancreatic Cancer, Adult
Additional relevant MeSH terms:
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Pancreatic Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Digestive System Neoplasms
Neoplasms by Site
Endocrine Gland Neoplasms
Digestive System Diseases
Pancreatic Diseases
Endocrine System Diseases
Antineoplastic Agents
Topoisomerase I Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Protective Agents
Physiological Effects of Drugs
Vitamin B Complex
Growth Substances