Phase I Trial of Intraperitoneal Bevacizumab in Refractory Malignant Ascites

Phase I Trial of Intraperitoneal Bevacizumab in Refractory Malignant Ascites.

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.

Study Overview

• Status: Unknown
• Conditions: Refractory Malignant Ascites
• Intervention / Treatment: Drug: bevacizumab

• Study Type: Interventional
• Enrollment (Anticipated): 18
• Phase: Phase 1

Contacts and Locations

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100142
      • Recruiting
      • Peking University Cancer Hospital
      • Contact: Lin Shen, M.D.; Phone Number: 861088196561; Email: lin100@medmail.com.cn
      • Contact: Jifang Gong, M.D.; Phone Number: 861088196561; Email: gongjifang@gmail.com
    • Beijing, Beijing, China, 100142
      • Active, not recruiting
      • Beijing Cancer Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: bevacizumab; The study evaluate 4 dose level of bevacizumab:2.5mg /kg;5 mg /kg;7.5mg /kg; 1.25mg /kg;	Drug: bevacizumab; Other Names: Avastin

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Peking University

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start: May 1, 2013
• Primary Completion (Anticipated): June 1, 2015
• Study Completion (Anticipated): June 1, 2015

Study Registration Dates

• First Submitted: May 8, 2013
• First Submitted That Met QC Criteria: May 10, 2013
• First Posted (Estimate): May 13, 2013

Study Record Updates

• Last Update Posted (Estimate): May 21, 2013
• Last Update Submitted That Met QC Criteria: May 19, 2013
• Last Verified: May 1, 2013

More Information

Terms related to this study

• Keywords: Bevacizumab; phase I; refractory malignant ascites; intraperitoneal
• Additional Relevant MeSH Terms: Pathologic Processes; Ascites; Physiological Effects of Drugs; Antineoplastic Agents; Antineoplastic Agents, Immunological; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Bevacizumab
• Other Study ID Numbers: CGOG6001