Trial Title:
The Efficacy of Bevacizumab and Serplulimab Combined With Recombinant Mutant HumanTumor Necrosis Factor(rmhTNF-NC) in the Treatment of Malignant Ascites
NCT ID:
NCT06433869
Condition:
Malignant Ascites
Conditions: Official terms:
Necrosis
Ascites
Bevacizumab
Immune Checkpoint Inhibitors
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Recruiting
Study design:
Allocation:
Non-Randomized
Intervention model:
Parallel Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
serplulimab
Description:
Additional intraperitoneal injection of bevacizumab or rmhTNF-NC is added to the PD-1
inhibitor.
Arm group label:
Group A
Arm group label:
Group B
Arm group label:
Group C
Other name:
PD-1 inhibitor
Intervention type:
Drug
Intervention name:
Bevacizumab
Description:
Intraperitoneal injection of bevacizumab is added to PD-1 inhibitor or rmhTNF-NC.
Arm group label:
Group A
Arm group label:
Group C
Intervention type:
Drug
Intervention name:
rmhTNF-NC
Description:
Intraperitoneal injection of rmhTNF-NC is added to PD-1 inhibitor or bevacizumab.
Arm group label:
Group B
Arm group label:
Group C
Other name:
recombinant human tumor necrosis factor
Summary:
1. More than half of peritoneal metastases are from digestive tract. Peritoneal
metastasis has poor prognosis, poor treatment response and limited means.
2. rmhTNF-NC or bevacizumab are effective in the treatment of malignant pleuroabdominal
effusion.
3, There is increasing evidence that PD-1/PD-L1 inhibitors in combination with vascular
endothelial growth factor receptor (VEGFR) inhibitors have a complementary mechanism of
action: VEGF pathway inhibitors normalize blood vessels in tumors and promote immune cell
maturation and infiltration, thus playing a synergistic role with ICIs. The strategy of
systemic immunotherapy combined with antivascular therapy has been confirmed by several
large phase III clinical trials such as IMbrave-150. Basic studies have confirmed that
uncontrolled tumor vessels in peritoneal metastasis and malignant ascites
microenvironment also play an important role in promoting disease progression. Therefore,
this project intends to explore the treatment of malignant abdominal effusion by local
intraperitoneal injection of bevacizumab and PD-1 on the basis of rmhTNF-NC
Detailed description:
GROUP A: serplulimab(PD-1 inhibitor)+bevacizumab GROUP B: serplulimab+rmhTNF-NC GROUP C:
serplulimab+bevacizumab+rmhTNF-NC
serplulimab(100mg,ip,D1、D15) bevacizumab(100mg,ip,D1、D15)
rmhTNF-NC(300IU/time,ip,D1、D4、D7、D10)
Criteria for eligibility:
Criteria:
Inclusion Criteria:
- Age ≥18 years old, gender unlimited;
- Malignant ascites confirmed by histology or cytology as originating from digestive
system tumors (malignant confirmed by ascites cytology or clinically diagnosed as
peritoneal metastases by imaging and symptoms);
- Patients with more than a moderate amount of abdominal fluid, who have failed
initial treatment or have been treated with conventional chemotherapy drugs and/or
biological response modulators intravenously. Moderate ascites is defined as:
- B ultrasound examination of ascites ≥3cm in lying position;
- Accompanied by clinical symptoms (chest tightness, shortness of breath,
abdominal distension and discomfort, which were judged by researchers to be
related to abdominal fluid accumulation);
- ECOG physical status is 0-2;
- Expected survival time >3 months;
- Cardiopulmonary function is basically normal;
- For adequate organ function, subjects must meet the following laboratory criteria:
- Peripheral blood imaging: WBC≥4.0×109/L, PLT≥80×109/L, Hb≥90g/L;
- Renal function: serum creatinine ≤2×ULN and creatinine clearance (calculated by
Cockcroft-Gault formula) ≥40 ml/min;
- Liver function: total bilirubin ≤1.5× upper limit of normal value (ULN); Or
total bilirubin >ULN but direct bilirubin ≤ ULN; Aspartate aminotransferase
(AST), alanine aminotransferase (ALT) ≤2.5×ULN (ALT or AST ≤5×ULN in patients
with liver metastasis);
- Good coagulation function, defined as International standardized ratio (INR) or
prothrombin time (PT) ≤1.5 times ULN;
- Thyroid stimulating hormone (TSH) ≤ULN; If abnormal, T3 and T4 levels and clinical
manifestations should be investigated, and comprehensive assessment of non-acute
activity can be included;
- Non-surgical sterilization or female patients of reproductive age who are required
to use a medically approved contraceptive method (such as an IUD, contraceptive pill
or condom) during the study treatment period and for 6 months after the end of the
study treatment period; Women of reproductive age who were not surgically sterilized
had to be negative for serum or urine HCG within 7 days prior to study enrollment.
And must be non-lactation period; For men whose partners are women of childbearing
age, effective contraception should be used during the trial and within 6 months
after the last administration of the study drug;
- Voluntarily enrolled in this study, with good compliance, signed written informed
consent, and able to cooperate with follow-up observation.
Exclusion Criteria:
- History of allergy to tumor necrosis factor and its derivatives, bevacizumab
analogues, and Serplulimab;
- Malignant diseases other than digestive tract neoplasms were diagnosed within 5
years prior to initial administration (excluding radical basal cell carcinoma of the
skin, squamous epithelial carcinoma of the skin, and/or carcinoma in situ after
radical resection);
- Received any other investigational drug therapy or participated in an interventional
clinical investigator within 7 days prior to initial dosing; Or received anti-tumor
drug treatment (including Chinese herbal medicine with anti-tumor indication) within
7 days prior to the first use of the study drug;
- Pregnant or lactating women, women of childbearing age who did not want to use
contraception during the study period; Or the man is unwilling to use effective
contraception during treatment and during the following 1 year;
- Significant damage to the function of important organs;
- Patients with obvious bleeding tendency;
- Clinically significant or uncontrolled heart disease, including unstable angina
pectoris, acute myocardial infarction within 6 months prior to first dosing, New
York Heart Association Class III/IV congestive heart failure, and uncontrolled
arrhythmia (in subjects who are allowed to wear a pacemaker or have atrial
fibrillation and have a well-controlled heart rate);
- Presence of ECG changes or medical history that investigators consider clinically
significant; Screening QTcF interval >480 ms, subjects with indoor block (QRS
interval >120 ms) can use JTc interval instead of QTc interval (if JTc is used
instead of QTc, JTc must be ≤340 ms);
- Uncontrolled hypertension, systolic blood pressure >160 mmHg or diastolic blood
pressure >100 mmHg after optimal medical treatment, history of hypertensive crisis
or hypertensive encephalopathy;
- Severe acute infection that is not under control; The patient is having fever (>
38℃), or has suppurative and chronic infection, and the wound is prolonged and does
not heal;
- Patients with encapsulated abdominal effusion confirmed by imaging; A definite
diagnosis of abdominal infection;
- Persons infected with acute or chronic active hepatitis B or hepatitis C, hepatitis
B virus (HBV) DNA>2000IU/ml or 104 copies /ml; Hepatitis C virus (HCV) RNA> 103
copies /ml; Hepatitis B surface antigen (HbsAg) and anti-HCV antibodies were both
positive. After nucleotide antiviral therapy, those who were lower than the above
criteria could be included in the group. A known history of human immunodeficiency
virus (HIV) infection or a confirmed positive immunotest result;
- Patients with obvious evidence of bleeding tendency or history within 3 months prior
to enrollment (hemorrhage >30 mL within 3 months, hematemesis, stool, and blood in
the stool), hemoptysis (>5 mL fresh blood within 4 weeks); People with a history of
inherited or acquired bleeding or coagulation disorders. Have clinically significant
bleeding symptoms or definite bleeding tendency within 3 months, such as
gastrointestinal bleeding, hemorrhagic gastric ulcer, etc.; Arterial or venous
thrombotic disease was present 6 weeks before enrollment;
- Known history of allogeneic organ transplantation and allogeneic hematopoietic stem
cell transplantation;
- Had a major surgical procedure (craniotomy, thoracotomy, or laparotomy) within 4
weeks prior to the first dose of study therapy or expected to require major surgery
during study therapy;
- Complications of toxicity and/or major surgery have not fully recovered before
starting treatment;
- Women who are pregnant or nursing, or who are expected to become pregnant or give
birth during the study period from screening visits to completion of safety
follow-up visits (male subjects to 90 days after the last dosing);
- Radiotherapy was received within 4 weeks prior to the first administration of the
study drug. Subjects must have fully recovered from radiation-related toxicities
without the need for corticosteroid therapy, confirming the rule out of radiation
pneumonia. For palliative radiotherapy for non-CNS disease, a 2-week washout period
is allowed;
- Patients with uncontrollable neurological, mental illness or mental disorder, poor
compliance, unable to cooperate with and describe the response to treatment;
Patients with uncontrolled primary brain tumor or central nervous metastases, with
obvious cranial hypertension or neuropsychiatric symptoms;
- There are other conditions that researchers consider inappropriate to participate in
this experiment.
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Cancer center of SunYat-sen University
Address:
City:
Guangzhou
Zip:
510060
Country:
China
Status:
Recruiting
Contact:
Last name:
Dongsheng Zhang, MD,PhD
Phone:
86-2087343795
Email:
zhangdsh@sysucc.org.cn
Facility:
Name:
Zhang Dongsheng
Address:
City:
Guangzhou
Country:
China
Status:
Recruiting
Contact:
Last name:
LU YUNXIN
Facility:
Name:
Zhang Dongsheng
Address:
City:
Guangzhou
Country:
China
Status:
Recruiting
Contact:
Last name:
ZHANG
Start date:
December 14, 2023
Completion date:
December 31, 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/NCT06433869
