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.|
|ClinicalTrials.gov Identifier: NCT03977233|
Recruitment Status : Recruiting
First Posted : June 6, 2019
Last Update Posted : May 26, 2020
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|
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.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||45 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|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|
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.
85 mg/m2 in 250 cc Dextrose solution given by IV on Day 1 of each 14-day cycle
Other Name: Eloxatin
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
400 mg/m2 bolus and then 2400 mg/m2 via continuous infusion on Day 1 of each 14-day cycle
Other Name: Adrucil
- 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.
- 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
- 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.
- 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.
- 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;
- 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.
- 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).
- 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.
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 ClinicalTrials.gov identifier (NCT number): NCT03977233
|Contact: Catherine Griffin, BS, BAemail@example.com|
|Contact: Brian Burgess, BSfirstname.lastname@example.org|
|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 email@example.com|
|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|
|Principal Investigator:||Autumn McRee, MD||University of North Carolina, Chapel Hill|