Clinical trial NCT06662006: Nal-IRI/5-FU/LV Chemotherapy Combined with PD-L1 Inhibitor and Multi-target Anti-angiogenic Small Molecule±SBRT As Second-line Therapy in Metastatic Pancreatic Cancer Patients
Official title: Efficacy and Safety of Second-line Therapy by Nal-IRI/5-FU/LV Chemotherapy Combined with PD-L1 Inhibitor and Multi-target Anti-angiogenic Small Molecule±SBRT in Metastatic Pancreatic Cancer Patients: a Prospective, Multicentre, Single-arm, Multi-cohort Study
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE2
Conditions: Advanced Metastatic Pancreatic Cancer
Keywords: pancreatic cancer
liposomal irinotecan
benmelstobart
anlotinib
Lead sponsor: The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School
Sponsor class: OTHER
First posted: 2024-10-28
Enrollment: 56
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This study is a single-arm, multi-center, multi-cohort, prospective clinical study initiated by the investigator.

The indication of this study is: patients with advanced metastatic pancreatic cancer who have progressed after first-line chemotherapy. Eligible patients will be assigned to liposomal irinotecan (nal-IRI) plus 5-fluorouracil (5-FU)/leucovorin (LV) (nal-IRI/5-FU/LV) combined with benmelstobart and anlotinib ± SBRT.

The total sample size for this study is expected to be 56 subjects.

Detailed description: For patients with advanced metastatic pancreatic cancer who failed first-line treatment, the screening and enrollment will be completed according to the enrollment and exclusion criteria described in the study protocol, and the informed consent form will be signed after full communication. After enrollment, patients will be treated with cohort A) or cohort B), and followed up regularly.

Cohort A: nal-IRI/5-FU/LV + PD-L1 inhibitor + multi-target anti-angiogenic small molecule:

Irinotecan liposome: 50mg/m2 IV D1, D15 LV: 400mg/m2 IV D1, D15 5-FU ：2.4g/m2 CIV 46h D1, D15 bemosubaemab: 1200mg IV Q3W Anlotinib: 12mg po D1-D14 Q3W

Cohort B: nal-IRI/5-FU/LV + PD-L1 inhibitor+ multi-target anti-angiogenic small molecule+SBRT Group:

Irinotecan liposomes: 50mg/m2 IV D1, D15 LV: 400mg/m2 IV D1, D15 5-FU ：2.4g/m2 CIV 46h D1, D15 bemosubaemab: 1200mg IV Q3W Anlotinib: 12mg po D1-D14 Q3W SBRT

Eligibility criteria: Inclusion Criteria:

1. Age ≥ 18 years and ≤ 75 years, ECOG score of ≤2 points, expected survival time ≥ 3 months.
2. Patients with histologically or cytologically confirmed advanced metastatic pancreatic cancer.
3. Imaging suggests distant measurable lesions.
4. Failure of first-line therapy and no use of fluorouracil, irinotecan, or liposomal irinotecan drugs in the first-line therapy.

Patients need to meet the following hematologic indicators e1. Neutrophil count ≥ 1.5×109/L e2. Hemoglobin ≥ 10 g/dL e3. Platelet count ≥ 100×109/L f. Patients need to meet the following biochemical parameters f1. Total bilirubin ≤ 1.5× upper limit of normal (ULN) f2. AST and ALT \&amp;lt;1.5×ULN f3. Creatinine clearance ≥ 60ml/min g. Patients of childbearing age need to take appropriate protective measures (contraception or other methods of birth control) before enrollment and during the trial.

H. Has signed an informed consent form. i. Able to follow the study protocol and follow-up process.

Exclusion Criteria:

1. Have received second-line or more anti-tumor therapy in the past.
2. First-line treatment with fluorouracil, irinotecan or liposomal irinotecan, etc.
3. Patient has a prior history of other tumors, unless it is cervical cancer in situ, treated squamous cell carcinoma or bladder epithelial tumors (Ta and TIS) or other malignancies that have received curative therapy (at least more than 5 years prior to enrollment).
4. Patient has an active bacterial or fungal infection (≥ 3rd edition NCI-CTC2 grade).

Patient has HIV, HCV, HBV infection, uncontrolled coronary artery disease or asthma, uncontrolled cerebrovascular disease or other disease deemed non-enrollable by the investigator.

f. Patients with autoimmune diseases or immunodeficiencies who should be treated with immunosuppressive drugs.

g. Pregnant and lactating women. Women of childbearing potential must have a negative pregnancy test within 7 days prior to enrollment.

h. Substance abuse, clinical or psychological, or social factors that compromise informed consent or study conduct.

i. Those who may be allergic to treatment drugs.

Primary outcomes:
measure: Objective effective rate (ORR)
timeFrame: 28 days per cycle, with ≤6 cycles of treatment expected per patient
Secondary outcomes:
measure: Disease control rate (DCR)
timeFrame: 28 days per cycle, with ≤6 cycles of treatment expected per patient
measure: Median overall survival (mOS)
timeFrame: 28 days per cycle, with ≤6 cycles of treatment expected per patient
measure: Median progression-free survival (mPFS)
timeFrame: 28 days per cycle, with ≤6 cycles of treatment expected per patient
Other outcomes:
measure: Exploring potential efficacy prediction biomarkers
timeFrame: 28 days per cycle, with ≤6 cycles of treatment expected per patient
Locations:
Study officials:
References: