Trial Title:
NALIRIFOX as Induction Therapy in LAPC
NCT ID:
NCT06467565
Condition:
Pancreatic Ductal Adenocarcinoma
Conditions: Official terms:
Adenocarcinoma
Irinotecan
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
Liposomal irinotecan
Description:
NALIRIFOX（Oxaliplatin 60 mg/m2 IV over 2 hours ; Liposomal Irinotecan 50 mg/m2 IV over 90
minutes ; Leucovorin(l-LV) 400 mg/m2 IV over 2 hours 5-fluorouracil 2.4 g/m2 for 46 hours
continuous infusion） on days 1 of a 14-day cycle.
Arm group label:
NALIRIFOX
Summary:
This is a prospective, single arm, single center, phase II study of NALIRIFOX as
conversion therapy in patients with locally advanced pancreatic cancer.
Detailed description:
Subjects will be treated with the NALIRIFOX regimen every 2 weeks in 4-weeks cycles
Imaging of tumor lesions will be performed after the subject has completed the first 2
cycles of treatment, and if the subject has not progressed, the subject will continue
treatment until surgical resection, disease progression (RECIST 1.1) or intolerable
toxicity, start of new anticancer drug therapy, withdrawal from the study, death, or loss
to follow-up. All treated subjects will be evaluated for response while on this treatment
every 8 weeks (±7) days after until surgical resection, disease progression (RECIST 1.1),
intolerable toxicity, start of new anticancer drug therapy, withdrawal from the study,
death, or loss to follow-up.. After 24 weeks of treatment, capecitabine or S-1 is the
maintenance regimen. Radiographic response will be evaluated every 12 weeks (± 7 days)
during the maintenance phase.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
1. Age ≥ 18 years old, ≤ 70 years old, male or female;
2. Understand the objectives and benefits and risks of the clinical trial, voluntarily
participate in and sign the informed consent form;
3. ECOG score 0-1;
4. The subject had histopathologically or cytologically confirmed type of pancreatic
ductal adenocarcinoma
5. Local progression according to the 2022 CSCO guidelines;
6. Initial subjects with locally advanced pancreatic cancer who have not undergone
resection of pancreatic tumor (except open exploration or internal drainage
surgery), chemotherapy, targeted, or immunotherapy.
7. At least one measurable pancreatic lesion per RECIST 1.1 criteria;
8. Expected survival time ≥ 3 months.
9. Heart, lung, liver, kidney and other major organ functions are basically normal.
10. Hematology tests should meet the following criteria (no blood transfusion, no use of
blood products, granulocyte colony-stimulating factor, or other hematopoietic growth
factors within 7 days prior to hematology):
1. White blood cell count ≥ 3.0 × 109/L and neutrophil count ≥ 1.5 × 109/L.
2. Platelet count ≥ 100 × 109/L.
3. Hemoglobin ≥ 90 g/L.
4. If component blood transfusions (red blood cells, platelets, etc.) are received
at screening, reexamination of hematology must be performed at 1-week intervals
before further screening can be considered.
11. Blood chemistry tests should meet the following criteria:
1. Plasma total bilirubin ≤ 1.5 × upper limit of normal.
2. ALT, AST, or ALP ≤ 2.5 × upper limit of normal;
3. Creatinine clearance ≥30 mL/min calculated by the Cockcroft-Gault formula
(Cockcroft-Gault formula: male Ccr = [(140-age) × body weight (kg)]/[0.818 ×
Scr (μmol/L)] or Ccr = (140-age) × body weight (kg)/72 × Scr (mg/dl), and
female Ccr calculated as male × 0.85);
12. The subject had no symptoms of cardiac insufficiency (NYHA functional class ≤ II) at
baseline and had no obvious abnormalities or abnormalities in electrocardiograms
that were not clinically significant.
13. Good compliance, voluntary compliance with this clinical trial protocol and
follow-up by the investigator during the study.
14. Subjects of childbearing potential voluntarily take highly effective contraceptive
measures in the trial.
15. Females must be non-lactating.
Exclusion Criteria:
1. Known allergy or intolerance to the ingredients or excipients of this
investigational product.
2. Any metastatic lesions.
3. Patients with unresolved acute or chronic infection
4. Other malignancies within 5 years (except cured basal cell carcinoma of the skin and
carcinoma in situ of the cervix);
5. Active hepatitis.
6. Patients with portal hypertension or cavernous transformation of the portal vein;
patients with gastrointestinal bleeding caused by tumor involving the digestive
tract; patients with intra-abdominal fistula or abscess due to tumor involvement of
digestive tract; the tumor encircles the celiac trunk or SMA and causes significant
vascular wall involvement (worm-like changes);
7. Presence of third space effusion that cannot be controlled by drainage or other
means (e.g., moderate-large pleural effusion, moderate-large pericardial effusion,
ascites); a small amount of pleural effusion or ascites that is not clinically
symptomatic and does not require clinical intervention should be strictly controlled
before enrollment.
8. Mental illness or mental disorder, poor compliance, unable to cooperate with
treatment
9. Patients with severe organic diseases or major organ failure, such as decompensated
heart and lung failure, which lead to intolerance to chemotherapy.
10. Abnormal coagulation (INR > 1.5, APTT > 1.5 ULN), bleeding tendency (e.g., active
ulcer lesions in the stomach, occult blood in stool (+ +), melena and/or hematemesis
within 3 months, hemoptysis) or near the location of the lesion to major vessels.
11. Patients with Grade I or higher coronary heart disease, arrhythmia (including QTc
prolongation > 450 ms in males and > 470 ms in females), taking arrhythmic drugs, or
associated underlying heart disease and cardiac insufficiency.
12. Patients with renal insufficiency, previous renal disease, and positive urine
protein (urine protein test 2 + or more, or 24-hour urineprotein quantitation > 1.0
g).
13. Organ transplant recipients.
14. There are drug addicts and other adverse drug addicts, long-term alcoholics and AIDS
and other infectious diseases.
15. Long-term use of corticosteroids or immunosuppressants.
16. Those who have received vaccines (including live and live attenuated vaccines)
within 4 weeks prior to enrollment, such as measles, mumps, rubella, varicella,
yellow fever, rabies, BCG, and typhoid (oral) vaccines, etc., or who plan to be
vaccinated during study dosing; Allowing all types of COVID-19 vaccines.
17. Subjects with active hepatitis B or hepatitis C (HBV DNA ≥ 1 × 104 copies or ≥ 2000
IU/mL regardless of drug control; hepatitis C infection, HCV RNA ≥ 15 IU/mL); or HIV
antibody positive (testing is not required if there is no clinical evidence of
possible HIV infection); or syphilis antibody (TPPA) positive.
18. Breast feeding, known pregnancy, positive serum pregnancy test or unwillingness to
use a reliable method of birth control, during therapy and for 6 months following
the last dose of nal-IRI. Females of Childbearing Potential must either agree to use
and be able to take effective contraceptive birth control measures (Pearl Index < 1)
or agree to use effective contraception during treatment and for at least 7 months
after last application of program treatment. Males with female partners of
reproductive potential should use condoms during treatment and for 4 months after
the last dose. A female subject is considered to be of childbearing potential unless
she is age ≥ 50 years and naturally amenorrhoeic for ≥ 2 years, or unless she is
surgically sterile. Males must agree not to father a child (including not donating
sperm) during the course of the trial and for at least 6 months after last
administration of study drugs.
19. In the opinion of the investigator, the subject is unable to complete the entire
trial process or other circumstances that are not suitable for participation in this
trial.
20. Use of strong inhibitors or inducers of CYP3A, CYP2C8 and UGT1A1. Subjects are
ineligible if:
- they are unable to discontinue the use of strong inhibitors of CYP3A, CYP2C8
and UGT1A1 at least 1 week prior to first dosing
- they are unable to discontinue the use of strong CYP3A and CYP2C8 inducers at
least 2 weeks prior to first dosing.
Gender:
All
Minimum age:
18 Years
Maximum age:
70 Years
Healthy volunteers:
No
Locations:
Facility:
Name:
The First Affiliated Hospital with Nanjing Medical University
Address:
City:
Nanjing
Zip:
025
Country:
China
Status:
Recruiting
Contact:
Last name:
KuiRong Jiang, archiater
Phone:
15312995688
Email:
Jiangkuirong@163.com
Investigator:
Last name:
Min Tu, associate doctor
Email:
Sub-Investigator
Start date:
December 25, 2023
Completion date:
December 31, 2025
Lead sponsor:
Agency:
The First Affiliated Hospital with Nanjing Medical University
Agency class:
Other
Source:
The First Affiliated Hospital with Nanjing Medical University
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06467565
