Back to resultsEvaluation of Safety and Efficacy of Electrochemotherapy in the Treatment of Pancreatic Adenocarcinoma
Primary Purpose
Pancreatic Adenocarcinoma
Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Electroporation
gemcitabine
nab-paclitaxel
Sponsored by
About this trial
This is an interventional treatment trial for Pancreatic Adenocarcinoma focused on measuring pancreatic adenocarcinoma, electrochemotherapy, electroporation, radiogenomics, imaging, magnetic resonance spectroscopy
Eligibility Criteria
Inclusion Criteria:
- Histologically or cytologically proven pancreatic carcinoma which is safely accessible by percutaneous methods;
- Locally advanced un-resectable pancreatic adenocarcinoma;
- At least one measurable lesion according to Response Evaluation Criteria In Solid Tumors (RECIST) criteria (longest diameter >=20 mm using conventional techniques or >=10 mm with spiral CT or MRI scan);
- WHO performance status (PS) < 2 or Eastern Cooperative Oncology Group < 2;
- Age >18;
- Life expectancy > 3 months;
- No history of gastric or esophageal varices;
- No active, uncontrolled infection;
- All patients must have adequate physiologic (hematologic, renal and hepatic) reserves as evidenced by: neutrophil count >1500/mL; platelet count >100,000/mL; serum creatinine <1.5x the upper limit of normal (ULN) value; serum glutamic-pyruvic transaminase (SGPT) <2.5 x ULN and bilirubin <1.5 x ULN functions
- Pain and biliary obstruction controlled before the start of the study
- Absence of psychological, familial, sociological, or geographical condition potentially hampering compliance with the study protocol and follow-up schedule;
- Women of childbearing potential (defined as sexually mature woman who 1) has not undergone hysterectomy [the surgical removal of the uterus] or bilateral oophorectomy [the surgical removal of both ovaries] or 2) has not been naturally post-menopausal for at last 24 consecutive months) must have a negative pregnancy test prior to starting therapy. Men and women of childbearing potential must be willing to use effective contraceptive while on treatment and for a reasonable period thereafter.
Exclusion Criteria:
- Prior chemotherapy with gemcitabine and nab-paclitaxel;
- Prior history of pancreatic electroporation;
- Untreatable contrast allergy;
- History of allergy or hypersensitivity to gemcitabine, nab-paclitaxel, or any of the excipients;
- Presence of metal biliary stent;
- Psychosis or seizures;
- Evidence of serious gastrointestinal bleeding or bowel obstruction;
- Pregnant or lactating women;
- Women of childbearing potential who are not using adequate protection;
- Inability to tolerate MRI imaging
Sites / Locations
- The University of Texas Health Science Center at Houston
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Electrochemotherapy with gemcitabine/nab-paclitaxel
Arm Description
During the first cycle of chemotherapy, patients will receive electroporation of the primary pancreatic tumor prior to administration of chemotherapy with gemcitabine and abraxane. The schedule of administration of gemcitabine and nab-paclitaxel will be administered as per standard of care. The chemotherapy schedule will include administration of nab-paclitaxel 125mg/m2 intravenous (IV) over approximately 30 to 45 minutes on Days 1, 8, and 15, followed by gemcitabine 1000mg/m2 IV infusion over approximately 30 minutes on days 1, 8, and 15 of each 28 day cycle.
Outcomes
Primary Outcome Measures
Number of participants who experienced dose limiting toxicities (DLTs)
A dose limiting toxicity (DLT) is any Grade 3 or 4 adverse event (AE) using the Common Terminology Criteria for Adverse Events Version 4.0 (CTCAE 4.0) that is possibly related to the electrochemotherapy treatment. CTCAE 4.0 Grade 3 is a severe AE and Grade 4 is a life-threatening or disabling AE. DLTs are collected to determine the Maximum Tolerated Dose (MTD), which is defined as as one field strength level less than the field strength at which two or more patients out of six total patients experience a DLT.
Secondary Outcome Measures
Number of participants who demonstrated no clinical change or clinical improvement in pancreatic adenocarcinoma outcome as assessed by time to progression
Time to progression is the time after treatment until tumor enlargement or metastatic disease is identified.
Number of participants who demonstrated no clinical change or clinical improvement in pancreatic adenocarcinoma outcome as assessed by one year survival
One year survival is the number of patients who are alive one year after treatment.
Number of participants who demonstrated no clinical change or clinical improvement in pancreatic adenocarcinoma outcome as assessed by tumor imaging
We will assess tumor size changes and tumor staging through magnetic resonance imaging (MRI).
Number of participants who demonstrated diffusion weighted magnetic resonance imaging (MRI) changes
Number of participants who demonstrated magnetic resonance spectroscopy (MRS) changes
Number of groups of patients who have similar pancreatic tumor gene expression characteristics and associated imaging characteristics after electrochemotherapy
Gene expression characteristics are identified by biopsy specimen evaluation. Imaging characteristics are evaluated by MRI and MRS.
Number of groups of patients who have similar pancreatic tumor gene expression characteristics and associated clinical outcomes after electrochemotherapy
Gene expression characteristics are identified by biopsy specimen evaluation. Clinical outcomes are evaluated by time to progression and 1 year survival. Time to progression is the time after treatment until tumor enlargement or metastatic disease is identified. One year survival is the number of patients who are alive one year after treatment.
Full Information
NCT ID
NCT02514421
First Posted
July 30, 2015
Last Updated
April 25, 2019
Sponsor
The University of Texas Health Science Center, Houston
1. Study Identification
Unique Protocol Identification Number
NCT02514421
Brief Title
Evaluation of Safety and Efficacy of Electrochemotherapy in the Treatment of Pancreatic Adenocarcinoma
Official Title
Evaluation of Safety and Efficacy of Electrochemotherapy in the Treatment of Pancreatic Adenocarcinoma
Study Type
Interventional
2. Study Status
Record Verification Date
April 2019
Overall Recruitment Status
Completed
Study Start Date
July 2015 (undefined)
Primary Completion Date
April 18, 2017 (Actual)
Study Completion Date
April 18, 2017 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
The University of Texas Health Science Center, Houston
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
Yes
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
The purpose of this study is to see how well electrochemotherapy works at treating people with Stage III pancreatic adenocarcinoma. Electrochemotherapy is a treatment that combines electroporation and chemotherapy administration. Electroporation uses an electric current to produce holes in pancreatic tumor, which causes the tumor cells to die or take up a higher concentration of administered chemotherapy agent. This study will test the safety and look at the effect of electrochemotherapy in the treatment of stage III pancreatic adenocarcinoma. This study will also help to find the safest and most effective amount of electroporation voltage to apply to this type of tumor.
Detailed Description
This is a phase I dose escalation trial using a 3 + 3 dose escalation scheme to evaluate the maximum tolerated field strength dose of administered irreversible electroporation in combination with chemotherapy. During the first cycle of chemotherapy, patients will receive electroporation of the primary pancreatic tumor prior to administration of chemotherapy with gemcitabine and nab-paclitaxel. The schedule of administration of gemcitabine and nab-paclitaxel will be administered as per standard of care. The investigators will use non-invasive dynamic magnetic resonance imaging and magnetic resonance spectroscopy to detect and describe changes within the tumor. Safety will be determined by assessing the number of class three or higher toxicity events in cohorts of 6 patients at progressively higher electroporation voltages. The maximum tolerated dose (MTD) will be defined as one voltage level less than the voltage at which two or more patients out of six total patients have a class three or higher toxicity event.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Pancreatic Adenocarcinoma
Keywords
pancreatic adenocarcinoma, electrochemotherapy, electroporation, radiogenomics, imaging, magnetic resonance spectroscopy
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
6 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Electrochemotherapy with gemcitabine/nab-paclitaxel
Arm Type
Experimental
Arm Description
During the first cycle of chemotherapy, patients will receive electroporation of the primary pancreatic tumor prior to administration of chemotherapy with gemcitabine and abraxane. The schedule of administration of gemcitabine and nab-paclitaxel will be administered as per standard of care. The chemotherapy schedule will include administration of nab-paclitaxel 125mg/m2 intravenous (IV) over approximately 30 to 45 minutes on Days 1, 8, and 15, followed by gemcitabine 1000mg/m2 IV infusion over approximately 30 minutes on days 1, 8, and 15 of each 28 day cycle.
Intervention Type
Device
Intervention Name(s)
Electroporation
Other Intervention Name(s)
Irreversible electroporation (IRE)
Intervention Description
Irreversible electroporation (IRE) will be performed under computed tomography (CT) guidance, during which 2 to 6 needles are advanced into the pancreatic tumor where a specified field strength will be applied.
Intervention Type
Drug
Intervention Name(s)
gemcitabine
Other Intervention Name(s)
Gemzar
Intervention Description
The chemotherapy schedule will include administration of gemcitabine 1000mg/m2 IV infusion over approximately 30 minutes on days 1, 8, and 15 of each 28 day cycle.
Intervention Type
Drug
Intervention Name(s)
nab-paclitaxel
Other Intervention Name(s)
Abraxane
Intervention Description
The chemotherapy schedule will include administration of nab-paclitaxel 125mg/m2 intravenous (IV) over approximately 30 to 45 minutes on Days 1, 8, and 15.
Primary Outcome Measure Information:
Title
Number of participants who experienced dose limiting toxicities (DLTs)
Description
A dose limiting toxicity (DLT) is any Grade 3 or 4 adverse event (AE) using the Common Terminology Criteria for Adverse Events Version 4.0 (CTCAE 4.0) that is possibly related to the electrochemotherapy treatment. CTCAE 4.0 Grade 3 is a severe AE and Grade 4 is a life-threatening or disabling AE. DLTs are collected to determine the Maximum Tolerated Dose (MTD), which is defined as as one field strength level less than the field strength at which two or more patients out of six total patients experience a DLT.
Time Frame
4 weeks
Secondary Outcome Measure Information:
Title
Number of participants who demonstrated no clinical change or clinical improvement in pancreatic adenocarcinoma outcome as assessed by time to progression
Description
Time to progression is the time after treatment until tumor enlargement or metastatic disease is identified.
Time Frame
1 year
Title
Number of participants who demonstrated no clinical change or clinical improvement in pancreatic adenocarcinoma outcome as assessed by one year survival
Description
One year survival is the number of patients who are alive one year after treatment.
Time Frame
1 year
Title
Number of participants who demonstrated no clinical change or clinical improvement in pancreatic adenocarcinoma outcome as assessed by tumor imaging
Description
We will assess tumor size changes and tumor staging through magnetic resonance imaging (MRI).
Time Frame
1 year
Title
Number of participants who demonstrated diffusion weighted magnetic resonance imaging (MRI) changes
Time Frame
1 year
Title
Number of participants who demonstrated magnetic resonance spectroscopy (MRS) changes
Time Frame
1 year
Title
Number of groups of patients who have similar pancreatic tumor gene expression characteristics and associated imaging characteristics after electrochemotherapy
Description
Gene expression characteristics are identified by biopsy specimen evaluation. Imaging characteristics are evaluated by MRI and MRS.
Time Frame
1 year
Title
Number of groups of patients who have similar pancreatic tumor gene expression characteristics and associated clinical outcomes after electrochemotherapy
Description
Gene expression characteristics are identified by biopsy specimen evaluation. Clinical outcomes are evaluated by time to progression and 1 year survival. Time to progression is the time after treatment until tumor enlargement or metastatic disease is identified. One year survival is the number of patients who are alive one year after treatment.
Time Frame
1 year
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Histologically or cytologically proven pancreatic carcinoma which is safely accessible by percutaneous methods;
Locally advanced un-resectable pancreatic adenocarcinoma;
At least one measurable lesion according to Response Evaluation Criteria In Solid Tumors (RECIST) criteria (longest diameter >=20 mm using conventional techniques or >=10 mm with spiral CT or MRI scan);
WHO performance status (PS) < 2 or Eastern Cooperative Oncology Group < 2;
Age >18;
Life expectancy > 3 months;
No history of gastric or esophageal varices;
No active, uncontrolled infection;
All patients must have adequate physiologic (hematologic, renal and hepatic) reserves as evidenced by: neutrophil count >1500/mL; platelet count >100,000/mL; serum creatinine <1.5x the upper limit of normal (ULN) value; serum glutamic-pyruvic transaminase (SGPT) <2.5 x ULN and bilirubin <1.5 x ULN functions
Pain and biliary obstruction controlled before the start of the study
Absence of psychological, familial, sociological, or geographical condition potentially hampering compliance with the study protocol and follow-up schedule;
Women of childbearing potential (defined as sexually mature woman who 1) has not undergone hysterectomy [the surgical removal of the uterus] or bilateral oophorectomy [the surgical removal of both ovaries] or 2) has not been naturally post-menopausal for at last 24 consecutive months) must have a negative pregnancy test prior to starting therapy. Men and women of childbearing potential must be willing to use effective contraceptive while on treatment and for a reasonable period thereafter.
Exclusion Criteria:
Prior chemotherapy with gemcitabine and nab-paclitaxel;
Prior history of pancreatic electroporation;
Untreatable contrast allergy;
History of allergy or hypersensitivity to gemcitabine, nab-paclitaxel, or any of the excipients;
Presence of metal biliary stent;
Psychosis or seizures;
Evidence of serious gastrointestinal bleeding or bowel obstruction;
Pregnant or lactating women;
Women of childbearing potential who are not using adequate protection;
Inability to tolerate MRI imaging
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Anil K Pillai, MD
Organizational Affiliation
The University of Texas Health Science Center, Houston
Official's Role
Principal Investigator
Facility Information:
Facility Name
The University of Texas Health Science Center at Houston
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
12. IPD Sharing Statement
Learn more about this trial
Evaluation of Safety and Efficacy of Electrochemotherapy in the Treatment of Pancreatic Adenocarcinoma
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