Clinical trial NCT02592395: Study of FOLFIRINOX Electrochemotherapy in the Treatment of Pancreatic Adenocarcinoma
Official title: Phase I Study of FOLFIRINOX Electrochemotherapy in the Treatment of Pancreatic Adenocarcinoma
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE1
Conditions: Pancreatic Adenocarcinoma
Keywords: pancreatic adenocarcinoma
electrochemotherapy
electroporation
radiogenomics
imaging
magnetic resonance spectroscopy
Lead sponsor: The University of Texas Health Science Center, Houston
Sponsor class: OTHER
First posted: 2015-10-30
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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 FOLFIRINOX. The schedule of administration of FOLFIRINOX 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.

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 FOLFIRINOX;
* 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

Primary outcomes:
measure: Number of participants who experienced dose limiting toxicities (DLTs)
timeFrame: 4 weeks
Secondary outcomes:
measure: Number of participants who demonstrated no clinical change or clinical improvement in pancreatic adenocarcinoma outcome as assessed by time to progression
timeFrame: 1 year
measure: Number of participants who demonstrated no clinical change or clinical improvement in pancreatic adenocarcinoma outcome as assessed by one year survival
timeFrame: 1 year
measure: Number of participants who demonstrated no clinical change or clinical improvement in pancreatic adenocarcinoma outcome as assessed by tumor imaging
timeFrame: 1 year
measure: Number of participants who demonstrated diffusion weighted magnetic resonance imaging (MRI) changes
timeFrame: 1 year
measure: Number of participants who demonstrated magnetic resonance spectroscopy (MRS) changes
timeFrame: 1 year
measure: Number of groups of patients who have similar pancreatic tumor gene expression characteristics after electrochemotherapy
timeFrame: 1 year
measure: Number of groups of patients who have similar imaging characteristics after electrochemotherapy
timeFrame: 1 year
measure: Number of groups of patients who have similar clinical outcomes after electrochemotherapy
timeFrame: 1 year
Other outcomes:
Locations:
Study officials:
affiliation: The University of Texas Health Science Center, Houston
name: Derek L West, MD, MS
role: PRINCIPAL_INVESTIGATOR
References: