Double-blind, placebo-controlled, randomized phase II-study investigating the efficacy of Bevacizumab for symptom control in patients with malignant ascites due to advanced-stage gastrointestinal cancers

• Conditions: patients with malignant ascites due to advanced-stage gastro-intestinal cancers; MedDRA version: 14.1Level: PTClassification code 10017758Term: Gastric cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 14.1Level: LLTClassification code 10015362Term: Esophageal cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 14.1Level: LLTClassification code 10056267Term: Gastroesophageal cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 14.1Level: LLTClassification code 10049010Term: Carcinoma hepatocellularSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 14.1Level: LLTClassification code 10008593Term: CholangiocarcinomaSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 14.1Level: PTClassification code 10061451Term: Colorectal cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 14.1Level: PTClassification code 10025538Term: Malignant ascitesSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 14.1Level: LLTClassification code 10033604Term: Pancreatic cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2009-014725-16-DE
• Lead Sponsor: AIO Studien gGmbH

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2009-09-25
• Last Update Posted: 27 January 2014

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: Not specified

Inclusion Criteria

1.Age >= 18 years
2.Written informed consent has been obtained prior to inclu¬sion into the study
3.Patient is capable and willing to comply with the study
4.Histologically confirmed esophageal, gastric, pancreatic, cholangiocellular, hepatocellular, or colorectal carcinoma
5.Cytologically confirmed ascites OR diagnosis of an exsudate (total protein in ascites > 30 g/l) clinically suggestive for malignant ascites OR morphological diagnosis of peritoneal carcinosis by CT , MRT or ultrasound
6.Ascites clinically judged as not responsive to conventional systemic therapies for primary malignancy
7.Ascites clinically judged as not responsive to diuretics
8.At the time of inclusion paracentesis required at least once within past 4 weeks. The first application of study medication must not take place later than 4 weeks after the preceding paracentesis in screening phase.
9.Before inclusion of the patient into the study, a 4-week screening period will allow for a stringent evaluation of the patient regarding fulfillment of inclusion and exclusion criteria. Importantly, no treatments for malignant ascites other than paracentesis and diuretics are allowed during the 4-week screening period.
10.ECOG performance score 0-3
11.Life expectancy > 12 weeks
12.Laboratory parameters:
Hematology
•Neutrophils > 1,500/µl
•Platelets > 100,000/µl
•Hemoglobin >= 9 g/dl or 5.59 mmol/l
Hemastasiology
•INR <= 1.5 x ULN and aPTT <= 1.5 x ULN within past 7 d
Clinical chemistry
•Creatinine clearance > 30 ml/min, serum creatinine < 2.5 x ULN
•Serum bilirubin < 3.0 x ULN
•Alkaline phosphatase and transaminases < 3.0 x ULN (in case of liver metastases < 7 x ULN)
Urinalysis:
•Patients with < 2+ proteinuria on dipstick urinalysis.
•Patients with >= 2+ proteinuria on dipstick urinalysis, who demonstrate < 2.0 g of protein/24 h on 24-h urine collection.

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 72
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 72

Exclusion Criteria

1.Concomitant malignancies other than gastrointestinal cancers (Patients with curatively treated basal and squamous cell carcino¬ma of the skin and / or in-situ carci¬noma of the cervix are eligible).
2.Bacterial peritonitis as indicated by laboratory results (neutrophil count > 250 / µl ascites) or clinical suspicion
3.Hemorrhagic ascites (ascites hematocrit > 2%)
5.Parallel treatment with anti-tumor agents other than the study medication from inclusion into the study until safety follow-up. Chemotherapy may be continued if started before screening phase (– 4 weeks before inclusion). Parallel Treatment with Bevacizumab i.v. is not allowed.
6.Therapy naïve patients
7.Parallel treatment of ascites with measures other than paracentesis, diuretics, and the study drugs from 4 weeks before inclusion into the study until safety follow-up.
8.Patients with extensive metastases of the liver making up > 70% of the total liver mass
9.Child C cirrhosis of the liver
10.Occlusion or thrombosis of the portal vein.
11.Evidence of current and symptomatic central nervous system (CNS) metastases or spinal cord compression.
12.12.Clinically significant cardiovascular diseases, e.g., un¬con¬trolled hypertension, uncontrolled arrhythmia, hemoptoe, cardiovascular accident within the last 6 months before treatment start, unstable angina, congestive heart failure (CHF) NYHA grade III/IV, symptomatic coronary heart disease, peripheral arterial disease stage >= II.
13.History of fistula formation involving an internal organ (e.g. tracheo-oesophagal, bronchopleural, biliary, vagina and bladder)
14.Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to study treatment start, or anticipation of the need for major surgical procedure during the course of the study.
15.Concomitant treatment with intravenous Bevacizumab for primary malignancy from inclusion into study until safety follow-up, Prior treatment with Bevacizumab for primary malignancy is not exclusionary.
16.Serious non-healing wound, ulcer or bone fracture.
17.Radiotherapy for purposes other than local control of symptoms.
18.Evidence of bleeding diathesis or coagulopathy.
19.Hematopoietic diseases.
20.Known intra-abdominal inflammatory process or serious gastrointestinal ulceration.
21.History of chronic intestinal diseases associated with severe diarrhea.
22.Thrombo-embolic events or severe hemorrhage (<= 6 months before treatment start).
23.Known hypersensitivity to the test drug Bevacizumab
24.Evidence of any other disease, metabolic dysfunction, physical examination finding, or laboratory finding giving reasonable suspicion of a disease or condition that contra-indicates the use of an investigational drug or puts the patient at high risk for treatment-related complications.
25.25.With the only exception of full dose (INR > 1.5) oral coumarin-derived anticoagulants, the use of full dose anticoagulants is allowed as long as the INR or a PTT is within therapeutic limits (according to the medical standard in the institution) and the patient has been on a stable dose for at least two weeks at the time of randomisation.
26.Patients who participated within the last 30 days prior to enrolment in a clinical trial and received a non approved investigational drug (e.g. follow up within the trial is not exclusionary).
27.Patients who have participated in this study before.
28.Women, lactating, pregnant or of childbearing potential and fertil

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified