Trial Title:
Sequential AG and mFOLFOX Combined With Serplulimab Injection and Bevacizumab Injection in Untreated Advanced Pancreatic Cancer
NCT ID:
NCT06393166
Condition:
Non-Resectable Pancreas Carcinoma
Conditions: Official terms:
Pancreatic Neoplasms
Bevacizumab
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:
Sequential AG and mFOLFOX in Combination With Serplulimab Injection and Bevacizumab Injection
Description:
Nab-paclitaxel:125 mg/m2, ivgtt, D1, 8 and 15,every 6 weeks for a treatment cycle
Gemcitabine hydrochloride: 1g/m2, ivgtt, D1, 8 and 15,every 6 weeks for a treatment cycle
5-FU: 2400 mg/m2 ,ivgtt over 46h, D29-30, every 6 weeks for a treatment cycle
Oxaliplatin: 85 mg/m2 ,ivgtt, D29, every 6 weeks for a treatment cycle LV: 400 mg/m2
,ivgtt over 2h, D29, every 6 weeks for a treatment cycle Serplulimab Injection:
3mg/kg,ivgtt,D1, every 2 weeks for a treatment cycle. Bevacizumab Injection:
5mg/kg,ivgtt,D1, every 2 weeks for a treatment cycle.
Arm group label:
Sequential AG and mFOLFOX in Combination With Serplulimab Injection and Bevacizumab Injection
Summary:
It is a single arm, open-label, multicenter, phase II cinical trial to evaluate the
efficacy and safety of the Sequential AG and mFOLFOX in Combination With Serplulimab
Injection and Bevacizumab Injection in first-line treatment of patients with Advanced or
Metastatic Pancreatic Cancer.
Detailed description:
It is a single arm, open-label, multicenter, phase II cinical trial to evaluate the
efficacy and safety of the Sequential AG and mFOLFOX in Combination With Serplulimab
Injection and Bevacizumab Injection in first-line treatment of patients with Advanced or
Metastatic Pancreatic Cancer. A Simon two-stage study design was utilized. Treatment will
continue until disease progression or toxicity is intolerable. The plan is to enroll 37
subjects in multiple hospitals in china.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
1. Voluntarily agree to participate in the study and sign the informed consent;
2. ≥18 years of age and ≤75 years of age on the day of signing the informed consent
form, regardless of gender;
3. Pancreatic ductal adenocarcinoma confirmed by pathologic histology or cytology;
4. No prior systemic therapy for unresectable locally advanced or metastatic pancreatic
cancer;
5. Measurable lesions at baseline according to RECIST 1.1 criteria; if the subject has
only 1 measurable lesion at baseline, the area of the lesion must not have received
radiotherapy in the past or there must be evidence of significant progression of the
lesion after completion of radiotherapy treatment;
6. the ECOG physical status score was 0 or 1 and the Expected survival ≥12 weeks;
7. No serious organic diseases of the heart, lungs, brain and other organs;
8. Adequate organ function
1. Bone Marrow Function: (no transfusion within 14 days prior to screening, no use
of granulocyte colony stimulating factor [G-CSF], no use of drug correction) :
i. Hemoglobin ≥90g/L; ii. Leukocytes ≥ 4.0 x 109/L, Neutrophils ≥1.5×109/L;
iii. Platelet ≥80×109/L;
2. Coagulation function: PT or APTT ≤ 1.5 x ULN in subjects not receiving
anticoagulation; if subjects are receiving anticoagulation, as long as the PT
is within the range of the anticoagulant drug formulation;
3. liver function: (no albumin infusion within 14 days prior to screening): Serum
total bilirubin ≤ 1.5 x ULN (with biliary obstruction, allowing enrollment of
subjects undergoing biliary drainage or in the midst of stenting therapy who
have a total bilirubin ≤ 2.5 x ULN). In subjects without liver metastasis,
Aspartate aminotransferase (AST), alanine aminotransferase (ALT)≤2.5×ULN; In
subjects with liver metastasis, ALT and AST≤5×ULN, but without elevated
bilirubin;
4. Renal function: serum creatinine ≤1.5 x ULN, creatinine clearance (CCr) ≥50
mL/min, urinary protein <2+ (if urinary protein ≥2+, 24-hour (h) urinary
protein quantification can be carried out, and 24h urinary protein
quantification <1.0 g can be enrolled)
5. Heart function: New York College of Cardiology (NYHA) rating < 3; Left
ventricular ejection fraction ≥50%;
9. Male or female patients of childbearing potential will voluntarily use an effective
method of contraception, such as a double-barrier contraceptive method, condoms,
oral or injectable contraceptives, and an intrauterine device (IUD), for the
duration of the study and up to 6 months after the last study dose. All female
patients will be considered of childbearing potential unless the female patient is
naturally menopausal, artificially menopausal or sterilized;
10. Subject's ability and willingness to comply with visits, treatment plans, laboratory
tests, and other study-related processes as specified in the study protocol.
Exclusion Criteria:
1. subjects with clear brain metastases on imaging or with meningeal metastases;
2. untreated spinal compression fractures not treated by surgery and/or radiotherapy;
treated spinal compression fractures require disease stabilization for at least 2
weeks prior to enrollment;
3. high risk of gastrointestinal or abdominal bleeding as evaluated by the
Investigator;
4. uncontrolled cancer pain; narcotic analgesics not at a stable dose at enrollment;
5. previous treatment with vascular endothelial growth factor (VEGFR) inhibitors or
previous treatment with immune checkpoint inhibitors;
6. antitumor treatment with chemotherapy, small molecule inhibitors, immunotherapy
(e.g., interleukin, interferon, or thymosin) within 28 days prior to enrollment in
this study, and herbal medicine with antitumor indications within 14 days prior to
dosing;
7. major surgical procedures [such as transabdominal, transthoracic and other major
surgeries; excluding diagnostic puncture such as ultrasonic endoscopy-guided
pancreatic fine-needle aspiration biopsy (EUS-FNB), percutaneous hepatic perforation
biopsy, peripheral venous catheterization, and biliary stent implantation] or
invasive treatments or operations with incomplete healing of the surgical incision,
local anti-tumor treatment such as hepatic artery interventional embolization,
hepatic metastasis cryo-ablation, radiofrequency ablation and other local anti-tumor
treatments. radiofrequency ablation and other local antitumor therapy;
8. have received radical radiotherapy within 3 months prior to study entry; palliative
radiotherapy 2 weeks prior to dosing is permitted, and the dose of radiotherapy
meets local standards of care for palliative care;
9. required systemic corticosteroid (>10 mg/day prednisone or equivalent of other
corticosteroid for ≥7 consecutive days) or immunosuppressive therapy within 14 days
prior to enrollment in this study; with the exception of inhaled or locally applied
hormones, or physiologic replacement doses of hormone therapy due to adrenal
insufficiency; short-term (≤7 days) corticosteroids are allowed for prophylaxis
(e.g., contrast allergy) or treatment of Non-autoimmune conditions (eg, delayed
hypersensitivity reactions caused by exposure to allergens) ;
10. subjects with uncorrectable albumin decline (serum albumin <3.0 g/dL) 14 days prior
to enrollment in this study; and
11. a 10% or greater weight loss in comparison to the weight loss at the time of ICF
signing within 72 hours prior to enrollment in this study; and
12. within 72 hours prior to study entry, the subject's ECOG physical status score
increases by ≥1 point compared to the ICF score; 13. within 28 hours prior to study
entry, the subject's ECOG physical status score increases by ≥1 point compared to
the ICF score; and
13. has received a live vaccine (including live attenuated vaccine) within 28 days prior
to enrollment in this study;
14. previous or current interstitial pneumonia/pneumatosis, unless determined by the
investigator to be inactive and not requiring hormonal therapy; and
15. pre-existing or current autoimmune disease, including but not limited to Crohn's
disease, ulcerative colitis, systemic lupus erythematosus, tuberculosis, Wegener's
syndrome (granulomatous disease with polyangiitis), Graves' disease, rheumatoid
arthritis, hypopituitarism, uveitis, autoimmune hepatitis, systemic sclerosis (
Scleroderma, etc.), Hashimoto's thyroiditis, autoimmune vasculitis, autoimmune
neuropathy (Guillain-Barre syndrome). The following conditions are excluded: type I
diabetes mellitus, hypothyroidism stabilized by hormone replacement therapy
(including hypothyroidism caused by autoimmune thyroid disease), psoriasis or
vitiligo that does not require systemic therapy;
16. a combination of other malignancies within the last 5 years, except cured squamous
skin cancer, basal cell carcinoma, non-basal invasive bladder cancer, and
prostate/cervical/breast cancer in situ;
17. hepatic metastases comprising more than 50% of the total liver volume;
18. uncontrolled comorbidities, including but not limited to the following
1. Active HBV or HCV infection; (Note: HBV DNA and/or HCV RNA testing is required
for subjects who are HBsAg positive and/or HCV antibody positive at Screening.
Subjects who are negative for HBV DNA ≤500 IU/mL (or ≤2000 copies/mL) and/or
HCV RNA are eligible for enrollment; HBsAg-positive subjects are required to
have their HBV DNA monitored during the course of treatment);
2. Known history of HIV infection or AIDS;
3. Active syphilis;
4. Active tuberculosis;
5. Active or uncontrolled serious infection (≥ CTCAE grade 2 infection);
6. Medication-uncontrolled hypertension (defined as systolic blood pressure ≥140
mmHg and/or diastolic blood pressure ≥90 mmHg;), symptomatic cardiac
insufficiency (NYHA II-IV), unstable angina pectoris or myocardial infarction
within 6 months, or the presence of a prolonged QTc or risk of torsades de
pointes (baseline QTc>470 msec (women)/450 msec (men) < Fridericia method
correction>, hypokalemia, long QT syndrome, atrial fibrillation with heart rate
>100 bpm at rest or severe cardiac valvular disease, history of medically
significant arrhythmias);
19. unrecovered toxicity from prior antitumor therapy to CTCAE ≤ Grade 1 (NCI-CTCAE
v5.0), except for baldness (any grade allowed) and peripheral neuropathy (recovery
to ≤ Grade 2 required);
20. history of prior allogeneic bone marrow or organ transplantation;
21. prior history of allergic reaction, hypersensitivity reaction, intolerance to
investigational drugs or similar medications; prior significant allergy to drugs or
foods or other substances (e.g., severe allergic reaction, immune-mediated
hepatotoxicity, immune-mediated thrombocytopenia, or anemia)
22. pregnant and/or lactating women;
23. other conditions that, in the opinion of the investigator, would affect the safety
of or adherence to treatment with the study medication, including alcoholism, drug
abuse, other serious illnesses (including psychiatric illnesses) that require
comorbid treatment, the presence of serious laboratory test abnormalities, moderate
to large amounts of plasmapheresis such as pleural fluid, pericardial effusion,
ascites, and other concomitant familial or social factors, which would affect the
safety of the patient;
Gender:
All
Minimum age:
18 Years
Maximum age:
75 Years
Healthy volunteers:
No
Locations:
Facility:
Name:
Zhejiang Cancer Hospital
Address:
City:
Hangzhou
Zip:
310022
Country:
China
Status:
Recruiting
Contact:
Last name:
Jieer Ying
Phone:
13858195803
Email:
hzyingjieer@163.com
Start date:
May 1, 2023
Completion date:
December 31, 2025
Lead sponsor:
Agency:
Zhejiang Cancer Hospital
Agency class:
Other
Source:
Zhejiang Cancer Hospital
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06393166
