Trial Title:
Hepatic Artery Chemotherapy for Patients With Localized Pancreas Cancer
NCT ID:
NCT05634720
Condition:
Pancreatic Ductal Adenocarcinoma
Conditions: Official terms:
Pancreatic Neoplasms
Conditions: Keywords:
PDAC
HA chemotherapy
FUDR
oxaliplatin
Study type:
Interventional
Study phase:
Phase 4
Overall status:
Recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Intervention model description:
We will include both patients planned to undergo surgery before chemotherapy, as well as
patients planned to receive systemic chemotherapy before surgery. This will allow us to
test the safety and feasibility of adding single-dose neoadjuvant HA chemotherapy prior
to surgery across the real-world treatment strategies employed in typical clinical
practice. All patients receive HA chemotherapy in addition to standard-of-care surgery
and systemic chemotherapy, so as not to withhold the treatment approach currently
associated with best outcomes.
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
HA Chemotherapy
Description:
On Day 1 of the treatment period, patients will undergo standard-of-care diagnostic
laparoscopy to confirm the absence of metastatic disease not seen on staging imaging, as
well as tissue acquisition (blood and liver biopsies) for pre-specified correlative
scientific studies. On Day 2 (±1 day), patients will receive the interventional
treatment, which is neoadjuvant HA chemotherapy. On Day 14 (±5 business days), patients
will undergo standard-of-care resection of their primary tumor, as well as tissue
acquisition (blood, liver biopsies, primary tumor, regional lymph nodes) for
pre-specified correlative scientific studies.
Arm group label:
PDAC with HA Chemotherapy
Summary:
This is a window-of-opportunity study which will evaluate the safety and feasibility of
single-dose neoadjuvant Hepatic Artery (HA) chemotherapy (FUDR/oxaliplatin) in patients
with localized pancreatic ductal adenocarcinoma (PDAC) eligible for surgical resection
and systemic chemotherapy.
Current standard-of-care therapy for patients with localized PDAC includes surgical
resection and six months of systemic chemotherapy. Because the sequence of these
treatments (surgery and chemotherapy) is not well established, we will include both
patients planned to undergo surgery before chemotherapy, as well as patients planned to
receive systemic chemotherapy before surgery. This will allow us to test the safety and
feasibility of adding single-dose neoadjuvant HA chemotherapy prior to surgery across the
real-world treatment strategies employed in typical clinical practice. Moreover, the
window-of-opportunity design is intended to make sure that all patients receive HA
chemotherapy in addition to standard-of-care surgery and systemic chemotherapy, so as not
to withhold the treatment approach currently associated with best outcomes.
The primary endpoint is safety and feasibility, and patients will be followed for 30 days
after resection of their primary tumors to assess these outcomes. Following the
short-term follow-up period, patients move to long-term follow-up, which will occur every
three months after resection of the primary tumor, for a period of up to three years.
Long-term secondary endpoints include disease free survival (DFS), liver metastasis-free
survival (LMFS), and overall survival (OS).
Detailed description:
This window-of-opportunity study will evaluate the safety and feasibility of single-dose
neoadjuvant HA chemotherapy (FUDR/oxaliplatin) in patients with localized PDAC eligible
for surgical resection and systemic chemotherapy. Current standard-of-care therapy for
patients with localized PDAC includes surgical resection and six months of systemic
chemotherapy. Because the sequence of these treatments (surgery and chemotherapy) is not
well established, we will include both patients planned to undergo surgery before
chemotherapy, as well as patients planned to receive systemic chemotherapy before
surgery. This will allow us to test the safety and feasibility of adding single-dose
neoadjuvant HA chemotherapy prior to surgery across the real-world treatment strategies
employed in typical clinical practice. Moreover, the window-of-opportunity design is
intended to make sure that all patients receive HA chemotherapy in addition to
standard-of-care surgery and systemic chemotherapy, so as not to withhold the treatment
approach currently associated with best outcomes.
During an initial screening period (0 to 28 days before the treatment period), informed
consent will be obtained and all inclusion/exclusion criteria will be confirmed for
participation. Once deemed appropriate for participation, patients will be enrolled and
begin study treatment. On Day 1 of the treatment period, patients will undergo
standard-of-care diagnostic laparoscopy to confirm the absence of metastatic disease not
seen on staging imaging, as well as tissue acquisition (blood and liver biopsies) for
pre-specified correlative scientific studies. On Day 2 (±1 day), patients will receive
the interventional treatment, which is neoadjuvant HA chemotherapy. On Day 14 (±5
business days), patients will undergo standard-of-care resection of their primary tumor,
as well as tissue acquisition (blood, liver biopsies, primary tumor, regional lymph
nodes) for pre-specified correlative scientific studies.
The primary endpoint is safety and feasibility, and patients will be followed for 30 days
after resection of their primary tumors to assess these outcomes. This includes safety
evaluations on treatment period Day 1 (diagnostic laparoscopy), Day 2 (±1 day, HA
chemotherapy), Day 4 (+2 business days), Day 14 (±5 business days, day of primary tumor
resection), every day throughout the perioperative hospitalization, and at outpatient
follow-up (30 days ±10 business days after surgery for resection of the primary tumor).
Following the short-term follow-up period, patients move to long-term follow-up, which
will occur every three months (±20 business days) after resection of the primary tumor,
for a period of up to three years. Long-term secondary endpoints include DFS, LMFS, and
OS.
As mentioned, a biobanking effort is built into this study to support prespecified
correlative scientific objectives. This includes acquisition of peripheral blood and
liver biopsies at the time of diagnostic laparoscopy (Day 1), acquisition of peripheral
blood, liver biopsies, the primary tumor, and regional lymph nodes at the time of
resection of the primary tumor (Day 14 ±5 days), and acquisition of peripheral blood at
outpatient follow-up appointments. Correlative studies include multisite immune
profiling, assessment of the HOMB both before and after HA chemotherapy, and dynamic
assessment of ctDNA.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
Patients are eligible to be included in the study only if they meet all of the following
criteria:
1. Histologically or cytologically confirmed diagnosis of PDAC, which is clinically
staged as either resectable or borderline resectable after multidisciplinary
evaluation.
2. Age >= 18 yo
3. ECOG Performance Status 0-1
4. Eligibility for FOLFIRINOX as determined by medical oncology and multidisciplinary
evaluation.
5. Women of child-bearing potential (i.e., women who are pre-menopausal or not
surgically sterile) must use accepted contraceptive methods (abstinence,
intrauterine device [IUD], oral contraceptive or double barrier device) during the
study and must have a negative serum or urine pregnancy test within 1 week of
neoadjuvant HA chemotherapy as well as during adjuvant chemotherapy as per SOC
practices.
6. Fertile men must practice effective contraceptive methods during the study, unless
documentation of infertility exists.
7. Expected survival >3 months.
8. Adequate laboratory parameters and organ function, namely:
1. Absolute neutrophil count (ANC) ≥ 1.5 x 109/L
2. Platelets ≥ 100 x 109/L
3. Hemoglobin (Hgb) ≥ 8 g/dL
4. Total bilirubin ≤ 1.5 x upper limit of normal (ULN)
5. ALT and AST ≤ 2.5 x ULN
6. Serum creatinine ≤ 1.5 x ULN or creatinine clearance (estimated) ≥ 50 cc/min by
Cockroft-Gault Formula (Appendix C)
9. Provide written, informed consent to participate in the study and follow the study
procedures.
Exclusion Criteria:
Patients will be excluded from the study if they meet any of the following criteria:
1. Hepatic arterial anatomy not amenable to percutaneous access, including any of the
following: celiac or superior mesenteric artery occlusion; accessory and replaced
left hepatic artery anatomy; accessory right hepatic artery anatomy; middle hepatic
artery anatomy; right gastric artery that originates more than 1 cm above the left
hepatic artery origin; any other variant anatomy deemed to have a risk of non-target
GI infusion; or incomplete hepatic perfusion from a separate left and right hepatic
artery.
2. CA 19-9 >500 within 2 weeks of planned surgical resection.
3. Pregnancy or breastfeeding.
4. Not willing to use an effective method of birth control.
5. History of other carcinomas diagnosed within the last two years, except cured
non-melanoma skin cancer, curatively treated in-situ cervical cancer, curatively
treated localized thyroid cancer, or localized prostate cancer treated curatively
with no evidence of biochemical or imaging recurrence.
6. Liver cirrhosis.
7. Prior liver surgery including partial hepatectomy or transplantation.
8. Active hepatitis or unresolved biliary obstruction at the time of diagnostic
laparoscopy, as evidenced by:
1. Total bilirubin > 1.5 x ULN
2. ALT and AST > 2.5 x ULN
9. Recent or current active infectious disease requiring systemic antivirals,
antibiotics or antifungals, or treatment within 2 weeks prior to the start of study
drug, including acute or chronic active hepatitis B or hepatitis C infection, or
uncontrolled HIV/AIDS. Patients with well controlled HIV are permitted. Patients
receiving prophylactic antibiotics (e.g., for prevention of urinary tract infection
or chronic obstructive pulmonary disease) are eligible.
10. Major surgical procedure, open biopsy, or significant traumatic injury within 28
days prior to the start of study or anticipation of need for major surgical
procedure during the course of the study other than surgical resection of the
pancreatic tumor.
11. Serious, non-healing wound, ulcer, or bone fracture.
12. History of allogenic hematopoietic stem cell transplantation.
13. Known hepatitis B virus (HBV) infection (e.g., positive hepatitis B surface antigen
[HBsAg]) or hepatitis C virus (HCV) infection (e.g., positive HCV ribonucleic acid
[RNA]).
14. Chronic treatment with systemic corticosteroids (> 10 mg daily prednisone
equivalents) or immunosuppressive medications
- Intermittent steroids (< 10 mg daily prednisone equivalents) may be used on an
as needed basis (e.g. for treatment of nausea, anorexia, and fatigue)
- Physiologic replacement doses of steroids due to adrenal insufficiency are
permitted in the absence of active autoimmune disease.
- Topical, inhaled, or intra-articular corticosteroids are allowed.
15. Participation in other interventional research protocols during the screening to 30
day follow up time-point.
16. Concurrent severe and/or uncontrolled medical conditions, which may compromise
participation in the study, including impaired heart function or clinically
significant heart disease
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Duke University Health System
Address:
City:
Durham
Zip:
27710
Country:
United States
Status:
Recruiting
Contact:
Last name:
Stacy Murray
Phone:
919-684-7983
Email:
stacy.murray@duke.edu
Start date:
January 2, 2024
Completion date:
June 30, 2028
Lead sponsor:
Agency:
Duke University
Agency class:
Other
Source:
Duke University
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05634720
