Trial Title:
Phase II Study of Sufantinib Combined With AG Versus AG First-line in the Treatment of LAPC or mPC
NCT ID:
NCT05969171
Condition:
Pancreatic Neoplasms
Conditions: Official terms:
Pancreatic Neoplasms
Gemcitabine
Albumin-Bound Paclitaxel
Paclitaxel
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:
Sofantinib、abraxane、gemcitabine
Description:
The combination of 3 weeks was a treatment cycle, and AG chemotherapy was defined as a
maximum of 6 treatment cycles, and soantinib was continued until disease progression (PD,
RECIST 1.1) or death (during patient treatment) or toxicity intolerance or other criteria
for discontinuation of study therapy were met in the protocol.
Arm group label:
Sofantinib in combination with abraxane and gemcitabine
Intervention type:
Drug
Intervention name:
Abraxane combined with gemcitabine
Description:
Abraxane combined with gemcitabine
Arm group label:
Abraxane combined with gemcitabine
Summary:
This is a single-center, open-label randomized controlled Phase II clinical study to
observe and evaluate the efficacy and safety of Sovantinib in combination with AG versus
AG first-line treatment in patients with locally advanced or metastatic pancreatic
cancer.
According to the literature analysis, the mPFS of gemcitabine combined with
albumin-binding paclitaxel in first-line treatment of metastatic pancreatic cancer was
3.56 months in historical controlled studies, and the expected PFS of soantinib combined
with AG regimen increased from 2.06 months to 4.5 months after 2 cycles of AG regimen.
Follow-up time was 12 months and enrollment time was 18 months. α=0.05 and β=0.2 were
used for bilateral test, and the PASS 22 software was used for analysis. The sample size
of AG group in the control group was 29 cases, and that of AG combined with Solvatinib in
the experimental group was 29 cases. The total sample size needed to be enrolled was 58
cases, and a total of 65 subjects were required according to the 10% shedding rate.
This study was divided into three stages: screening period, treatment period and
follow-up period. During treatment, tumor status was assessed by imaging every 6 weeks
(±7 days) until disease progression (PD, RECIST 1.1) or death (during patient treatment)
or toxicity intolerance or other protocol criteria for discontinuation of study therapy
were met. A maximum of 6 treatment cycles of AG chemotherapy were specified, and
soantinib was continued until disease progression (PD, RECIST 1.1) or death (during
patient treatment) or toxicity intolerance or other criteria for discontinuation of study
therapy were met in the protocol. Tumor treatment and survival status after disease
progression were recorded. Safety outcomes included AE, changes in laboratory test
values, vital signs and electrocardiogram changes.
Detailed description:
This is a single-center, open-label randomized controlled Phase II clinical study to
observe and evaluate the efficacy and safety of solantinib combined with AG versus AG
first-line therapy in patients with locally advanced or metastatic pancreatic cancer.
According to the literature analysis, the mPFS of gemcitabine combined with albumin-bound
paclitaxel in first-line treatment of metastatic pancreatic cancer in historical control
studies was 3.56 months, and the PFS of solantinib combined with AG regimen was expected
to increase from 2.06 months to 4.5 months after 2 cycles of AG regimen. Follow-up time
was 12 months and enrollment time was 18 months. α=0.05 and β=0.2 were used for bilateral
test, and PASS 22 software was used for analysis. The sample size of AG group in the
control group was 29 cases, and that of AG combined with solvatinib in the experimental
group was 29 cases. The total sample size required to be enrolled was 58 cases, and a
total of 65 subjects were required according to the calculation of 10% shedding rate.
The study was divided into three stages: screening period, treatment period and follow-up
period. During treatment, the tumor was evaluated by imaging every 6 weeks (±7 days)
until disease progression (PD, RECIST 1.1) or death (during the patient's treatment) or
toxicity became intolerable or other protocol criteria for discontinuation of study
therapy were met. It is specified that AG chemotherapy should not exceed a maximum of 8
treatment cycles, and that solantinib should be continued until disease progression (PD,
RECIST 1.1) or death (in the course of patient treatment) or toxicity becomes intolerable
or other criteria for discontinuation of study therapy as specified in the protocol are
met. The tumor treatment and survival status after disease progression were recorded.
Safety outcome measures included AE, changes in laboratory test values, vital signs and
electrocardiogram changes.
Researchers can add unplanned imaging tests for tumors as clinically necessary.
Subjects must meet all of the following criteria for enrollment:
1. The subjects voluntarily joined the study and signed the informed consent with good
compliance and follow-up;
2. Unresectable, locally advanced or metastatic pancreatic cancer confirmed by
histopathology or cytology;
3. Aged between 18 and 75 (including 18 and 75), male or female;
4. ECOG score: 0-1; Expected survival ≥12 weeks;
5. Patients who had previously received 2 cycles of AG regimen first-line systemic
therapy for locally advanced or metastatic pancreatic cancer and whose efficacy was
evaluated as CR, PR, SD (excluding SD patients whose efficacy was evaluated as
increased after 2 cycles of therapy);
6. Patients with postoperative distant metastasis had received adjuvant chemotherapy of
one type and the distance from adjuvant therapy time > Patients with recurrence
at 6 months could be included in the group;
7. At least one measurable lesion (according to RECIST 1.1 criteria); Magnetic
resonance imaging (MRI) enhancement or computed tomography (CT) enhancement
accurately measured the diameter of ≥10mm, conventional CT scan to determine the
diameter of at least 20mm.
8. No serious organic diseases of heart, lung, brain and other organs;
9. The functions of major organs and bone marrow are basically normal:
1. Blood routine: white blood cells ≥ 4.0 x 109/L, neutrophils ≥ 1.5 x 109/L,
platelets ≥ 80 x 109/L, hemoglobin ≥ 90g/L;
2. International Standardized ratio (INR) and activated partial thrombin time
(APTT) ≤1.5× upper limit of normal value (ULN);
3. Liver function: serum total bilirubin ≤ 1.5 x ULN, ALT/AST ≤ 3 x ULN, serum
total biliary red ≤ 1.5 x ULN after internal/external drainage for obstructive
jaundice;
4. Renal function: serum creatinine ≤ 1.5 x ULN, creatinine clearance (CCr) ≥
50mL/min;
5. Normal cardiac function, left ventricular ejection fraction (LVEF)≥50% by
two-dimensional echocardiography;
10. Fertile male or female patients volunteered to use effective contraceptive methods,
such as double screen contraceptives, condoms, oral or injectable contraceptives,
intrauterine devices, etc., during the study period and within 6 months of the last
study medication. All female patients will be considered fertile unless they have
undergone natural menopause, artificial menopause or sterilization.
Those who met each of the above criteria were included in the study.
The study proposal shall be excluded if any of the following criteria are met:
1. Participated in clinical trials of other antitumor drugs within 4 weeks before
enrollment;
2. Prior treatment with VEGFR inhibitors or prior treatment with immune checkpoint
inhibitors;
3. Patients with BRCA1/2 germ line mutation;
4. Patients with obstructive jaundice but failing to reach the expected yellow
reduction;
5. Have had other malignancies within the past 5 years, other than basal cell or
squamous cell carcinoma of the skin after radical surgery, or carcinoma in situ of
the cervix;
6. Patients who have had or currently have any brain metastases;
7. The investigators determined that liver metastases accounted for 70% or more of the
total liver volume;
8. Had received any surgery (except biopsy) or invasive treatment or operation within 4
weeks prior to inclusion, and the surgical incision was not completely healed
(except intravenous catheterization, puncture drainage, internal/external drainage
for obstructive jaundice, etc.);
9. Uncontrolled pleural effusion, pericardial effusion or ascites requiring drainage;
10. Local antitumor therapy, such as hepatic artery interventional embolization, liver
metastasis cryoablation or radiofrequency ablation, was received within 4 weeks
before enrollment;
11. Electrolyte abnormalities identified by the investigator as clinically significant;
12. The patient has medically uncontrolled hypertension, as follows: systolic blood
pressure ≥140 mmHg and/or diastolic blood pressure ≥90 mmHg;
13. Urine routine indicated urinary protein ≥2+ and 24-hour urinary protein volume >
1.0g;
14. Patients whose tumors are judged to be at high risk of invading vital blood vessels
and causing fatal haemorrhage during the follow-up study;
15. Patients with significant evidence or history of bleeding tendency within 3 months
prior to enrollment (bleeding within 3 months > 30 mL, hematemesis, black feces,
blood in stool), hemoptysis (within 4 weeks > 5 mL fresh blood); A history of
hereditary or acquired bleeding or a coagulation disorder. Have clinically
significant bleeding symptoms or definite bleeding tendency within 3 months, such as
gastrointestinal bleeding, hemorrhagic gastric ulcer, etc.;
16. Clinically significant cardiovascular disease, including but not limited to acute
myocardial infarction, severe/unstable angina, or coronary artery bypass grafting
within 6 months prior to enrollment; New York Heart Association (NYHA) Grades for
Congestive Heart Failure > Level 2; Ventricular arrhythmias requiring medical
treatment; Electrocardiogram (ECG) showed a QT c interval ≥480 ms;
17. Active or uncontrolled severe infection (≥CTCAE grade 2 infection);
18. Unmitigated toxic reactions higher than CTCAE grade 2 or above due to any previous
anticancer therapy, excluding grade 2 or less neurotoxicity due to alopecia,
lymphocytopenia, and oxaliplatin;
19. Women who are pregnant (positive pregnancy test before medication) or breastfeeding;
20. Any other medical condition, clinically significant metabolic abnormality, physical
abnormality or laboratory abnormality, which, in the investigator's judgment, the
patient has a medical condition or condition that is reasonably suspected to be
unsuitable for the use of the study drug (such as the presence of epileptic seizures
requiring treatment), or which would interfere with the interpretation of the study
results, or place the patient at high risk;
21. Known human immunodeficiency virus (HIV) infection; A known history of clinically
significant liver disease, including viral hepatitis [active HBV infection must be
ruled out as a known carrier of hepatitis B virus (HBV), i.e. positive HBV DNA
(>1×104 copies /mL or > 2000 IU/ml); known hepatitis C virus infection (HCV)
and HCV RNA positive (>1×103 copies /mL), or other hepatitis, cirrhosis;
22. The presence of any active, known or suspected autoimmune disease (including but not
limited to: myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus
erythematosus, rheumatoid arthritis, enteritis, multiple sclerosis, vasculitis,
glomerulonephritis, uveitis, pituitaritis, hyperthyroidism, etc.);
23. Allergy or suspected allergy to the study drug or similar drug;
24. In the investigator's judgment, the patient had other factors that might affect the
study results or lead to the termination of the study, such as alcoholism, drug
abuse, other serious medical conditions (including mental illness) requiring
concomitant treatment, serious laboratory abnormalities, and family or social
factors that would affect the patient's safety.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
Subjects must meet all of the following criteria for enrollment:
1. The subjects voluntarily joined the study and signed the informed consent with good
compliance and follow-up;
2. Unresectable, locally advanced or metastatic pancreatic cancer confirmed by
histopathology or cytology;
3. Aged between 18 and 75 (including 18 and 75), male or female;
4. ECOG score: 0-1; Expected survival ≥12 weeks;
5. Patients who had previously received 2 cycles of AG regimen first-line systemic
therapy for locally advanced or metastatic pancreatic cancer and whose efficacy was
evaluated as CR, PR, SD (excluding SD patients whose efficacy was evaluated as
increased after 2 cycles of therapy);
6. Patients with postoperative distant metastasis had received adjuvant chemotherapy of
one type and the distance from adjuvant therapy time > Patients with recurrence
at 6 months could be included in the group;
7. At least one measurable lesion (according to RECIST 1.1 criteria); Magnetic
resonance imaging (MRI) enhancement or computed tomography (CT) enhancement
accurately measured the diameter of ≥10mm, conventional CT scan to determine the
diameter of at least 20mm.
8. No serious organic diseases of heart, lung, brain and other organs;
9. The functions of major organs and bone marrow are basically normal:
1. Blood routine: white blood cells ≥ 4.0 x 109/L, neutrophils ≥ 1.5 x 109/L,
platelets ≥ 80 x 109/L, hemoglobin ≥ 90g/L;
2. International Standardized ratio (INR) and activated partial thrombin time
(APTT) ≤1.5× upper limit of normal value (ULN);
3. Liver function: serum total bilirubin ≤ 1.5 x ULN, ALT/AST ≤ 3 x ULN, serum
total biliary red ≤ 1.5 x ULN after internal/external drainage for obstructive
jaundice;
4. Renal function: serum creatinine ≤ 1.5 x ULN, creatinine clearance (CCr) ≥
50mL/min;
5. Normal cardiac function, left ventricular ejection fraction (LVEF)≥50% by
two-dimensional echocardiography;
10. Fertile male or female patients volunteered to use effective contraceptive methods,
such as double screen contraceptives, condoms, oral or injectable contraceptives,
intrauterine devices, etc., during the study period and within 6 months of the last
study medication. All female patients will be considered fertile unless they have
undergone natural menopause, artificial menopause or sterilization.
Those who met each of the above criteria were included in the study.
Exclusion Criteria:
The study proposal shall be excluded if any of the following criteria are met:
1. Participated in clinical trials of other antitumor drugs within 4 weeks before
enrollment;
2. Prior treatment with VEGFR inhibitors or prior treatment with immune checkpoint
inhibitors;
3. Patients with BRCA1/2 germ line mutation;
4. Patients with obstructive jaundice but failing to reach the expected yellow
reduction;
5. Have had other malignancies within the past 5 years, other than basal cell or
squamous cell carcinoma of the skin after radical surgery, or carcinoma in situ of
the cervix;
6. Patients who have had or currently have any brain metastases;
7. The investigators determined that liver metastases accounted for 70% or more of the
total liver volume;
8. Had received any surgery (except biopsy) or invasive treatment or operation within 4
weeks prior to inclusion, and the surgical incision was not completely healed
(except intravenous catheterization, puncture drainage, internal/external drainage
for obstructive jaundice, etc.);
9. Uncontrolled pleural effusion, pericardial effusion or ascites requiring drainage;
10. Local antitumor therapy, such as hepatic artery interventional embolization, liver
metastasis cryoablation or radiofrequency ablation, was received within 4 weeks
before enrollment;
11. Electrolyte abnormalities identified by the investigator as clinically significant;
12. The patient has medically uncontrolled hypertension, as follows: systolic blood
pressure ≥140 mmHg and/or diastolic blood pressure ≥90 mmHg;
13. Urine routine indicated urinary protein ≥2+ and 24-hour urinary protein volume >
1.0g;
14. Patients whose tumors are judged to be at high risk of invading vital blood vessels
and causing fatal haemorrhage during the follow-up study;
15. Patients with significant evidence or history of bleeding tendency within 3 months
prior to enrollment (bleeding within 3 months > 30 mL, hematemesis, black feces,
blood in stool), hemoptysis (within 4 weeks > 5 mL fresh blood); A history of
hereditary or acquired bleeding or a coagulation disorder. Have clinically
significant bleeding symptoms or definite bleeding tendency within 3 months, such as
gastrointestinal bleeding, hemorrhagic gastric ulcer, etc.;
16. Clinically significant cardiovascular disease, including but not limited to acute
myocardial infarction, severe/unstable angina, or coronary artery bypass grafting
within 6 months prior to enrollment; New York Heart Association (NYHA) Grades for
Congestive Heart Failure > Level 2; Ventricular arrhythmias requiring medical
treatment; Electrocardiogram (ECG) showed a QT c interval ≥480 ms;
17. Active or uncontrolled severe infection (≥CTCAE grade 2 infection);
18. Unmitigated toxic reactions higher than CTCAE grade 2 or above due to any previous
anticancer therapy, excluding grade 2 or less neurotoxicity due to alopecia,
lymphocytopenia, and oxaliplatin;
19. Women who are pregnant (positive pregnancy test before medication) or breastfeeding;
20. Any other medical condition, clinically significant metabolic abnormality, physical
abnormality or laboratory abnormality, which, in the investigator's judgment, the
patient has a medical condition or condition that is reasonably suspected to be
unsuitable for the use of the study drug (such as the presence of epileptic seizures
requiring treatment), or which would interfere with the interpretation of the study
results, or place the patient at high risk;
21. Known human immunodeficiency virus (HIV) infection; A known history of clinically
significant liver disease, including viral hepatitis [active HBV infection must be
ruled out as a known carrier of hepatitis B virus (HBV), i.e. positive HBV DNA
(>1×104 copies /mL or > 2000 IU/ml); known hepatitis C virus infection (HCV)
and HCV RNA positive (>1×103 copies /mL), or other hepatitis, cirrhosis;
22. The presence of any active, known or suspected autoimmune disease (including but not
limited to: myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus
erythematosus, rheumatoid arthritis, enteritis, multiple sclerosis, vasculitis,
glomerulonephritis, uveitis, pituitaritis, hyperthyroidism, etc.);
23. Allergy or suspected allergy to the study drug or similar drug;
24. In the investigator's judgment, the patient had other factors that might affect the
study results or lead to the termination of the study, such as alcoholism, drug
abuse, other serious medical conditions (including mental illness) requiring
concomitant treatment, serious laboratory abnormalities, and family or social
factors that would affect the patient's safety.
Gender:
All
Minimum age:
18 Years
Maximum age:
75 Years
Healthy volunteers:
No
Locations:
Facility:
Name:
Fudan University ShangHai Cancer Center
Address:
City:
Shanghai
Country:
China
Contact:
Last name:
Jin Xu
Phone:
18017317267
Email:
xujin@fudanpci.org
Start date:
August 2023
Completion date:
July 2025
Lead sponsor:
Agency:
Fudan University
Agency class:
Other
Source:
Fudan University
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05969171
