Trial Title:
Surufatinib and Serplulimab Combined With AG Regimen Compare With AG Regimen as Conversion Therapy for Patients With Locally Advanced Pancreatic Cancer (SAGE)
NCT ID:
NCT05988372
Condition:
Locally Advanced Pancreatic Cancer
Conditions: Official terms:
Pancreatic Neoplasms
Paclitaxel
Albumin-Bound Paclitaxel
Gemcitabine
Conditions: Keywords:
Locally Advanced Pancreatic Cancer
Conversion Therapy
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Not yet recruiting
Study design:
Allocation:
Randomized
Intervention model:
Parallel Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
Surufatinib + Serplulimab+Albumin-paclitaxel + Gemcitabine
Description:
Surufatinib:250mg orally once a day for 3 weeks(3 weeks 1 cycle) Serplulimab:4.5mg/Kg by
intravenous infusions on day1 every 3 weeks Albumin-paclitaxel:125mg/m2 by intravenous
infusions on day1 and 8 every 3 weeks Gemcitabine:1000mg/m2 by intravenous infusions on
day1 and 8 every 3 weeks
Arm group label:
Surufatinib + Serplulimab+Albumin-paclitaxel + Gemcitabine
Intervention type:
Drug
Intervention name:
Albumin-paclitaxel + Gemcitabine
Description:
Albumin-paclitaxel:125mg/m2 by intravenous infusions on day1 and 8 every 3 weeks
Gemcitabine:1000mg/m2 by intravenous infusions on day1 and 8 every 3 weeks
Arm group label:
Albumin-paclitaxel + Gemcitabine
Summary:
This is a Phase II Randomized Controlled PILOT clinical study. The purpose of this study
is to explore the efficacy and safety of surufatinib and serplulimab in combination with
albumin-paclitaxel and gemcitabine in the conversion therapy for patients with
unresectable locally advanced pancreatic cancer. Furthermore, it compares the efficacy of
surufatinib and serplulimab in combination with albumin-paclitaxel and gemcitabine to the
albumin-paclitaxel and gemcitabine regimen in the conversion therapy for patients with
unresectable locally advanced pancreatic cancer.
Detailed description:
A total of 50 participants are expected to be enrolled in this study; 25 will receive the
surufatinib and serplulimab in conjunction with albumin-paclitaxel and gemcitabine
regimen and 25 will receive the AG regimen. The participants who have been enrolled will
initially undergo two cycles of albumin-paclitaxel and gemcitabine induction
chemotherapy. The researcher will assess the patients' efficacy based on their imaging
results after the second cycle. Patients with PD will be excluded from this trial, and
patients with SD, PR, or CR will be enrolled. Patients will be randomly chosen to receive
either the AG regimen for 2-4 cycles or the surufatinib combined with serplulimab and AG
regimen for 2-4 cycles. Every two cycles, the researcher assessed the effectiveness of
the patients' treatments and the potential for R0 resection. Then, patients with PD were
removed from the group, those who could be operated were enrolled for surgical resection,
and those without PD and unable to undergo surgery were finished with a total of 6 cycles
of either the AG regimen chemotherapy or surufatinib combined with serplulimab and the AG
regimen chemotherapy. Within 12 weeks of surgery, patients underwent 0-2 cycles of
chemotherapy with the AG regimen or surufatinib combined with serplulimab and AG regimen,
totaling 6 cycles of postoperative chemotherapy. Then patients of AG group will enter
follow up stage. Patients with R0 resection will accept surufatinib in combination with
serplulimab maintenance for no longer than 12 cycles after surgery, or until
intolerability, progressive disease, death, or other criteria for study treatment
discontinuation specified in the protocol, whichever comes first. Patients who have not
progressed and are unable to undergo surgery, or who accepted R1 or R2 resection, after
six cycles of the surufatinib combination with serplulimab and AG regimen, will receive
sulfatinib combined with serplulimab maintenance therapy for a maximum of 29 cycles, or
until intolerance, disease progression, death, or other criteria specified in the study
protocol were met.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
1. Written informed consent obtained from the patient prior to treatment.
2. Pathologically confirmed unresectable locally advanced pancreatic cancer, received
no surgical therapy.
3. Age between 18 and 75 years at the time of study entry.
4. Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1.
5. Measurable or evaluable lesions according to RECIST v1.1 criteria.
6. Life expectancy ≥ 12 weeks.
7. There are no serious organic diseases of the heart, lungs, brain and other organs.
8. Adequate functioning of the bone marrow and major organs function meeting the
following criteria:
1. White blood cell count ≥ 4 × 109/L, Neutrophil count ≥ 1.5 × 109/L, Platelets
count ≥ 100 × 109/L,Hemoglobin ≥ 90 g/L.
2. Normal coagulation function, without active bleeding or thrombotic diseases:
INR ≤ 1.5 × ULN, APTT ≤ 1.5 × ULN.
3. Liver function: Total serum bilirubin ≤ 1.5 ×ULN, Serum aspartate
aminotransferase (AST) and serum alanine aminotransferase (ALT) ≤ 3 × ULN,
Obstructive Jaundice with total serum bilirub ≤ 1.5 x ULN after internal/
external drainage.
4. Kidney function: Serum creatinine ≤ 1.5 × upper limit of normal (ULN) or
creatinine clearance ≥ 60 mL/min.
5. Cardiac function:left ventricular ejection fraction (LVEF) of 50%≥ on 2D
cardiac ultrasound.
9. Male or female patients of potential for childbearing who voluntarily used effective
contraceptive methods such as double-barrier contraception, condoms, oral or
injection avoidance or pregnancy medications, IUDs, etc during the study period and
within 6 months of the last study medication . All female patients will be
considered fertile unless the female patient is naturally menopausal.
Exclusion Criteria:
1. Participants diagnosed pancreatic cancer with distant metastases.
2. Participation in other antineoplastic drug clinical trials within 4 weeks prior to
enrollment;
3. Previous systemic antitumor therapy (chemotherapy, radiation, targeted or immunoth,
etc.).
4. Diagnosis of any second malignancy, except for adequately treated basal cell skin
cancer or in situ carcinoma of the cervix uteri.
5. Known allergy or hypersensitivity to any of the study drugs or any of the study drug
excipients.
6. Active or prior documented autoimmune or inflammatory disorders.
7. Participants are being treated with immunosuppressants, or systemic or absorbable
topical hormones for immunosuppressive purposes (dose> 10 mg/day prednisone or other
equivalent hormones) , and the use is still continued within 2 weeks before
enrollment.
8. Have undergone any surgery (other than biopsy) or invasive treatment or manipulation
within 4 weeks prior to enrollment and the surgical incision has not healed
completely (except intravenous catheterization, puncture drainage, internal or
external drainage of obstructive jaundice, etc.)
9. Participants with abnormal thyroid function who were unable to maintain thyroid
function within the normal range with medical treatment.
10. Hypertension that cannot be controlled in the presence of optimal treatment is
defined as systolic blood pressure ≥ 150 mmHg and/or diastolic blood pressure ≥ 100
mmHg.
11. Urinary routine showed that urinary protein ≥2+, and 24-hour urinary protein>1.0g.
12. Participantst currently has any disease or condition that affects the absorption of
the drug, or the participants cannot take sulfatinib orally
13. participants with evidence or history of significant bleeding tendency within 3
months prior to enrollment (bleeding>30 mL within 3 months with hematemesis, melena,
hematochezia), hemoptysis (fresh blood>5 mL within 4 weeks); Patients with history
of hereditary or acquired bleeding or coagulation dysfunction, with clinically
significant bleeding symptoms or definite bleeding tendency within 3 months, such as
gastrointestinal bleeding and hemorrhagic gastric ulcer.
14. Cardiovascular disease of significant clinical significance, including but not
limited to acute myocardial infarction, severe/unstable angina, or coronary bypass
grafting within 6 months prior to enrollment; New York Heart Association (NYHA)
grade > 2 for congestive heart failure; ventricular arrhythmias requiring drug
therapy; Electrocardiogram (ECG) showing QT interval ≥480 ms;
15. Severe infection that is active or uncontrolled:
1. Inherited or acquired immunodeficiency disease,
2. Known clinically significant history of liver disease, including viral
hepatitis [known hepatitis B virus (HBV) carriers must exclude active HBV
infection , HBV DNA positive (>1×104 copies/mL or >2000 IU/ml)];
3. known hepatitis C virus infection (HCV) and positive HCV RNA (>1×103 copies/ml)
or other hepatitis, cirrhosis.
16. Pregnant or lactating women or participants with family planning during the trial
period.
17. Participants have a known history of psychotropic substance abuse, alcoholism, or
drug abuse.
18. The investigator believes that the participant has any clinical or laboratory
abnormalities or other reasons that are unsuitable for this clinical study.
Gender:
All
Minimum age:
18 Years
Maximum age:
75 Years
Healthy volunteers:
No
Locations:
Facility:
Name:
First Affiliated Hospital, Sun Yat-Sen University
Address:
City:
Guangzhou
Zip:
510080
Country:
China
Contact:
Last name:
Kuang Ming
Phone:
008687755766
Phone ext:
8576
Email:
kuangm@mail.sysu.edu.cn
Start date:
October 23, 2023
Completion date:
October 23, 2026
Lead sponsor:
Agency:
Sun Yat-sen University
Agency class:
Other
Source:
Sun Yat-sen University
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05988372
