Phase I Trial of Intraperitoneal Bevacizumab in Refractory Malignant Ascites

Study Overview
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Brief Summary
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Malignant ascites often has a profound impact on the quality of life of cancer patients. Current treatments,including dietary, medical, and procedural are often temporary and unsatisfactory options in patients approaching the end of life. Intraperitoneal bevacizumab for the palliation of malignant ascites might be a novel choice for refractory malignant ascites.

Official Title
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Phase I Trial of Intraperitoneal Bevacizumab in Refractory Malignant Ascites.

Conditions
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Refractory Malignant Ascites

Intervention / Treatment
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* Drug: bevacizumab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Signed informed consent form; Histologically or cytologically confirmed non-squamous cell carcinoma，including colorectal cancer, gastric cancer, esophageal cancer, pancreatic cancer, bile duct cancer, ovarian cancer, peritoneal primary tumor;Ascites were diagnosed by ultrasound or CT and confirmed malignant ascites by cytology; failed to standard systemic therapy and / or no appropriate treatment for the treatment for malignant ascites Age 18-70 years; Performance Status- Eastern Cooperative Oncology Group (ECOG)≤2; Life expectancy of at least 8 weeks; Exclusion Criteria: systematic anti-cancer therapy, including chemotherapy (intraperitoneal chemotherapy), radiation therapy, immunotherapy, biological or hormone therapy performed within 2 weeks; tyrosine kinase inhibitors or monoclonal antibodies of anti-vascular endothelial growth factor (VEGF) performed within 4 weeks; Laboratory tests:Absolute neutrophil count<1.0x109/L,Platelet count<75x 109/L,Hemoglobin<8g/dl,PT-INR≥1.5 times upper limit of normal (ULN);Bilirubin≥2 x ULN,AST and ALT≥2.5 times ULN(no liver metastasis),≥5 times ULN(with liver metastasis)Creatinine≥1.5 times ULN or calculated creatinine clearance, using the Cockcroft-Gault formula,<40 mL/min; uncontrolled hypertension:systolic pressure ≥160 mmHg,or diastolic pressure≥100mmHg Known history of severe heart disease,uncontrolled or symptomatic angina, congestive heart failure,clinically significant arrhythmias,myocardial infarction within six months; active (severe or uncontrolled) bleeding (hemorrhage within 3 months> 30 ml), hemoptysis (fresh blood, 4 weeks> 5 ml), bloody ascites thrombosis, tumor thrombus events (including arterial/venous thrombosis, tumor thrombosis, pulmonary embolism, transient ischemic attack)within 12 months; Portal hypertensive disease or severe liver disease, including various types of cirrhosis, obstructive jaundice; concurrent gastrointestinal obstruction, peptic ulcer, Crohn's disease, ulcerative colitis and other gastrointestinal diseases according to investigators' determination that may cause gastrointestinal bleeding or perforation; concurrent severe respiratory disease, or chronic therapy with oxygen or corticosteroids, such as chronic obstructive pulmonary disease, interstitial lung disease, etc. Unresolved or unstable, serious toxicity from prior cancer treatment (any toxicities greater than grade 2 or not recovered from surgery; Symptomatic brain metastasis; Uncontrolled systemic disease,such as infection,unstable diabetes mellitus,etc; Active infection of HIV、HBV、HCV； Major surgery within 4 weeks of start of study treatment, without complete recovery. Pregnant or lactating women.Negative serum pregnancy test (For women of childbearing potential);Fertile patients must use effective contraception. Dementia, altered mental status, or any psychiatric condition that would prevent the understanding or rendering of ICF; Received any investigational drug treatment within 4 weeks of start of study treatment.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: bevacizumab<br>The study evaluate 4 dose level of bevacizumab:2.5mg /kg;5 mg /kg;7.5mg /kg; 1.25mg /kg; | Drug: bevacizumab<br> <br> * Other names: Avastin;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| adverse events | participants will be followed for the duration of hospital stay, an expected average of 1 week | during the treatment in the hospital,an expected average of 1 week | 
| Maximum tolerated dose | during the treatment in the hosptital | 1 week | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective response rate | ultrasound will be performed every week for efficacy evaluation | 1 week | 
| time to treatment failure(TTF) | the follow-up visit of time to TTF will be performed every 4 weeks | 1 month | 
| time to death(TTD) | TTD means that from the first dose of treatment drug to death or lost, the follow-up visit will be performed every 2 months till death or lost | 2 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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phase I, refractory malignant ascites, Bevacizumab, intraperitoneal