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Malignant AscitesPhase 2NCT06433869

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

A Phase 2 study testing serplulimab, Bevacizumab and rmhTNF-NC in people with Malignant Ascites, run by Sun Yat-sen University at 3 sites in China.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Malignant Ascites
What is being tested?
serplulimab, Bevacizumab and rmhTNF-NC
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
60 participants
Where
3 sitesChina
Study dates
14 Dec 2023to 31 Dec 2026
Phase
Phase 2
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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;
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  • 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.

Who cannot join

  • 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;
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  • 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.

Trial locations and contacts

3 sites in 1 country. Contact the study team or a site near you to ask about taking part.

dongsheng zhang, PHD contact

020-87343533

zhangdsh@sysucc.org.cn

yunxin LU, PHD contact

020-87343533

luyx@sysucc.org.cn

China3 sites, 3 recruiting

  • Cancer center of SunYat-sen University

    Guangzhou, Guangdong, 510060

    Dongsheng Zhang, MD,PhD, 86-2087343795, zhangdsh@sysucc.org.cn

    Recruiting

  • Zhang Dongsheng

    Guangzhou

    LU YUNXIN

    Recruiting

  • Zhang Dongsheng

    Guangzhou

    ZHANG

    Recruiting

Other trials in China

About this study

Official title: Multi-arm, Phase II Clinical Study of Intraperitoneal Injection of Recombinant Human Tumor Necrosis Factor, Bevacizumab Monoclonal Antibody, and Serplulimab for the Treatment of Malignant Ascites Patients With Standard Therapy Failure

  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

Read the 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)

Being tested
serplulimab, Bevacizumab, rmhTNF-NC

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • serplulimabDrug

    Also called PD-1 inhibitor

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

  • BevacizumabDrug

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

  • rmhTNF-NCDrug

    Also called recombinant human tumor necrosis factor

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

Study groups in NCT06433869
Study groupRoleWhat they receive
Group AExperimentalTreat the malignant ascites by local intraperitoneal injection of PD-1 inhibitor and bevacizumab
Receives: Drug: serplulimab; Drug: Bevacizumab
Group BExperimentalTreat the malignant ascites by local intraperitoneal injection of PD-1 inhibitor and rmhTNF-NC
Receives: Drug: serplulimab; Drug: rmhTNF-NC
Group CExperimentalTreat the malignant ascites by local intraperitoneal injection of PD-1 inhibitor, rmhTNF-NC and bevacizumab
Receives: Drug: serplulimab; Drug: Bevacizumab; Drug: rmhTNF-NC

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Objective response rate of ascites

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

    Measured: 2 months

Secondary outcomes (4)

  1. Duration of ascites relief

    Time since first CR or PR to PD

    Measured: 1 years

  2. Ascites control rate

    percentage of patients achieving CR, PR and SD.

    Measured: 2 months

  3. Incidence of Treatment-Emergent Adverse Events

    Adverse events according to the NCI CTCAE 5.0

    Measured: 2 months

  4. The score of chronic abdominal effusion function scale changed

    Measured by FACIT-AI,score range 1 to 5, higher scores mean a better

    Measured: 2 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted30 May 2024
  2. Study start14 Dec 2023
  3. Primary completion31 Dec 2026 (estimated)
  4. Study completion31 Dec 2026 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
60 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT06433869
Sponsor's protocol ID
HPPMS-001
Status last verified
May 2024
First submitted
23 Apr 2024
Last updated
30 May 2024
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
Undecided

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing serplulimab, Bevacizumab and rmhTNF-NC in people with Malignant Ascites, run by Sun Yat-sen University at 3 sites in China.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 16 inclusion and 20 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 30 May 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 3 sites in China. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact dongsheng zhang, PHD (020-87343533, zhangdsh@sysucc.org.cn), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Objective response rate of ascites (time frame: 2 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT06433869.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 May 2024.

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