Clinical trial NCT01852409: Phase I Trial of Intraperitoneal Bevacizumab in Refractory Malignant Ascites
Official title: Phase I Trial of Intraperitoneal Bevacizumab in Refractory Malignant Ascites.
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
Conditions: Refractory Malignant Ascites
Keywords: refractory malignant ascites
Bevacizumab
intraperitoneal
phase I
Lead sponsor: Peking University
Sponsor class: OTHER
First posted: 2013-05-13
Enrollment: 18
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: Inclusion Criteria:

1. Signed informed consent form;
2. 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;
3. failed to standard systemic therapy and / or no appropriate treatment for the treatment for malignant ascites
4. Age 18-70 years;
5. Performance Status- Eastern Cooperative Oncology Group (ECOG)≤2;
6. Life expectancy of at least 8 weeks;

Exclusion Criteria:

1. systematic anti-cancer therapy, including chemotherapy (intraperitoneal chemotherapy), radiation therapy, immunotherapy, biological or hormone therapy performed within 2 weeks;
2. tyrosine kinase inhibitors or monoclonal antibodies of anti-vascular endothelial growth factor (VEGF) performed within 4 weeks;
3. 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;
4. uncontrolled hypertension:systolic pressure ≥160 mmHg,or diastolic pressure≥100mmHg
5. Known history of severe heart disease,uncontrolled or symptomatic angina, congestive heart failure,clinically significant arrhythmias,myocardial infarction within six months;
6. active (severe or uncontrolled) bleeding (hemorrhage within 3 months\> 30 ml), hemoptysis (fresh blood, 4 weeks\> 5 ml), bloody ascites
7. thrombosis, tumor thrombus events (including arterial/venous thrombosis, tumor thrombosis, pulmonary embolism, transient ischemic attack)within 12 months;
8. Portal hypertensive disease or severe liver disease, including various types of cirrhosis, obstructive jaundice;
9. 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;
10. concurrent severe respiratory disease, or chronic therapy with oxygen or corticosteroids, such as chronic obstructive pulmonary disease, interstitial lung disease, etc.
11. Unresolved or unstable, serious toxicity from prior cancer treatment (any toxicities greater than grade 2 or not recovered from surgery;
12. Symptomatic brain metastasis;
13. Uncontrolled systemic disease,such as infection,unstable diabetes mellitus,etc;
14. Active infection of HIV、HBV、HCV；
15. Major surgery within 4 weeks of start of study treatment, without complete recovery.
16. Pregnant or lactating women.Negative serum pregnancy test (For women of childbearing potential);Fertile patients must use effective contraception.
17. Dementia, altered mental status, or any psychiatric condition that would prevent the understanding or rendering of ICF;
18. Received any investigational drug treatment within 4 weeks of start of study treatment.

Primary outcomes:
measure: adverse events
timeFrame: during the treatment in the hospital,an expected average of 1 week
measure: Maximum tolerated dose
timeFrame: 1 week
Secondary outcomes:
measure: Objective response rate
timeFrame: 1 week
measure: time to treatment failure(TTF)
timeFrame: 1 month
measure: time to death(TTD)
timeFrame: 2 months
Other outcomes:
Locations:
city: Beijing
country: China
facility: Beijing Cancer Hospital
state: Beijing
city: Beijing
country: China
facility: Peking University Cancer Hospital
state: Beijing
Study officials:
References:
citation: Kou F, Gong J, Li Y, Li J, Zhang X, Li J, Shen L. Phase I study of intraperitoneal bevacizumab for treating refractory malignant ascites. J Int Med Res. 2021 Feb;49(2):300060520986664. doi: 10.1177/0300060520986664.