The Efficacy of Bevacizumab and Serplulimab Combined With Recombinant Mutant HumanTumor Necrosis Factor(rmhTNF-NC) in the Treatment of Malignant Ascites

NCT06433869 | Recruiting Phase 2

• 1 other identifier: HPPMS-001
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 3

Brief Summary

1. 1.More than half of peritoneal metastases are from digestive tract. Peritoneal metastasis has poor prognosis, poor treatment response and limited means.
2. 2.rmhTNF-NC or bevacizumab are effective in the treatment of malignant pleuroabdominal effusion.

Conditions

Malignant Ascites

Outcome Measures

Primary Outcomes (1)

• Objective response rate of ascites

  Defined as the percentage of patients achieving CR or PR according to the WHO criteria detected by ultrasound.

  2 months

Secondary Outcomes (4)

• Duration of ascites relief

  1 years

• Ascites control rate

  2 months

• Incidence of Treatment-Emergent Adverse Events

  2 months

• The score of chronic abdominal effusion function scale changed

  2 months

Study Arms (3)

Group A

EXPERIMENTAL

Treat the malignant ascites by local intraperitoneal injection of PD-1 inhibitor and bevacizumab

Drug: serplulimab; Drug: Bevacizumab

Group B

EXPERIMENTAL

Treat the malignant ascites by local intraperitoneal injection of PD-1 inhibitor and rmhTNF-NC

Drug: serplulimab; Drug: rmhTNF-NC

Group C

EXPERIMENTAL

Treat the malignant ascites by local intraperitoneal injection of PD-1 inhibitor, rmhTNF-NC and bevacizumab

Drug: serplulimab; Drug: Bevacizumab; Drug: rmhTNF-NC

Interventions

serplulimab DRUG

Additional intraperitoneal injection of bevacizumab or rmhTNF-NC is added to the PD-1 inhibitor.

Also known as: PD-1 inhibitor

Group A; Group B; Group C

Bevacizumab DRUG

Intraperitoneal injection of bevacizumab is added to PD-1 inhibitor or rmhTNF-NC.

Group A; Group C

rmhTNF-NC DRUG

Intraperitoneal injection of rmhTNF-NC is added to PD-1 inhibitor or bevacizumab.

Also known as: recombinant human tumor necrosis factor

Group B; Group C

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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;

You may not qualify if:

• 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;

Sponsors & Collaborators

• Sun Yat-sen University: lead

Study Sites (3)

Cancer center of SunYat-sen University

Guangzhou, Guangdong, 510060, China

RECRUITING

Zhang Dongsheng

Guangzhou, China

RECRUITING

Zhang Dongsheng

Guangzhou, China

RECRUITING

MeSH Terms

Interventions

Immune Checkpoint Inhibitors; Bevacizumab; recombinant human tumor necrosis factor-binding protein-1

Intervention Hierarchy (Ancestors)

Molecular Mechanisms of Pharmacological Action; Pharmacologic Actions; Chemical Actions and Uses; Antineoplastic Agents, Immunological; Antineoplastic Agents; Therapeutic Uses; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Central Study Contacts

dongsheng zhang, PHD

CONTACT

020-87343533; zhangdsh@sysucc.org.cn

yunxin LU, PHD

CONTACT

020-87343533; luyx@sysucc.org.cn

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director

Study Record Dates

• First Submitted: April 23, 2024
• First Posted: May 30, 2024
• Study Start: December 14, 2023
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2026
• Last Updated: May 30, 2024

Record last verified: 2024-05

Locations

CN (3)