Open-label study of bevacizumab (AVASTIN®) in combination with platinum-containing chemotherapy as first-line treatment of patients with advanced or recurrent non-squamous non-small cell lung cancer - SAIL

• Register: EUCTR
• Last refreshed on: 19 March 2012
• Main ID: EUCTR2005-005887-97-SE
• Date of registration: 29/06/2006
• Prospective Registration: Yes
• Primary sponsor: F. Hoffmann-La Roche Ltd
• Public title: Open-label study of bevacizumab (AVASTIN®) in combination with platinum-containing chemotherapy as first-line treatment of patients with advanced or recurrent non-squamous non-small cell lung cancer - SAIL
• Scientific title: Open-label study of bevacizumab (AVASTIN®) in combination with platinum-containing chemotherapy as first-line treatment of patients with advanced or recurrent non-squamous non-small cell lung cancer - SAIL
• Date of first enrolment: 15/08/2006
• Target sample size: 2000
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2005-005887-97
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: no Randomised: no Open: yes Single blind: no Double blind: no Parallel group: no Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: Placebo: Other:

Countries of recruitment

Austria, Czech Republic, Denmark, Estonia, Finland, Germany, Hungary, Iceland, Italy, Latvia, Lithuania, Netherlands, Portugal, Slovenia, Spain, Sweden, United Kingdom

Key inclusion & exclusion criteria

Inclusion criteria:
Patients included in the study should have the following criteria:

1. Written informed consent (informed consent document to be approved by the institution’s Independent Ethics Committee and patient consent obtained prior to any study-specific procedure)

2. Age =18 years

3. Able to comply with the protocol

4. Histologically or cytologically documented inoperable, locally advanced (Stage IIIb with supraclavicular lymph node metastases or malignant pleural or pericardial effusion), metastatic (Stage IV) or recurrent non-squamous NSCLC

5. ECOG PS 0-2

6. Life expectancy =12 weeks

7. Adequate haematological function
- Absolute neutrophil count (ANC) =1.5 x 10[9]/L AND
- Platelet count =100 x 10[9]/L AND
- Haemoglobin =9 g/dL (may be transfused to maintain or exceed this level)

8. Adequate liver function
- Total bilirubin <1.5 x ULN AND
- Asparagine aminotransferase (AST), alanine aminotransferase (ALT) <2.5 x ULN in patients without liver metastases; <5 x ULN in patients with liver metastases

9. Adequate renal function
- Serum creatinine =1.25 x ULN or calculated creatinine clearance =50 mL/min AND
- Urine dipstick for proteinuria <2+. Patients discovered to have =2+ proteinuria on dipstick urinalysis at baseline should undergo a 24 hour urine collection and must demonstrate =1 g of protein in 24 hours

10. INR =1.5 and partial prothrombin time (PTT or aPTT) =1.5 x ULN within 7 days prior to enrolment

11. If female, should not be pregnant or be breast-feeding. Women with an intact uterus (unless amenorrhoeic for the last 24 months) must have a negative serum pregnancy test within 28 days prior to enrolment into the study. If a serum pregnancy test is not performed within 7 days prior to the first dose of bevacizumab, a confirmatory urine test (within 7 days prior to the first dose of bevacizumab) is required.

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
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
Patients with any of the following will be excluded from study entry:

1. Mixed, non-small cell and small cell tumours or mixed adenosquamous carcinomas with a predominant squamous component

2. History of haemoptysis, defined as bright red blood of at least half a teaspoon in the 3 months prior to enrolment

3. Evidence of tumour invading major blood vessels on imaging. The investigator or the local radiologist must exclude evidence of tumour that is fully contiguous with, surrounding, or extending into the lumen of a major blood vessel (e.g. pulmonary artery or superior vena cava)

4. Evidence of CNS metastases, even if previously treated. If suspected, the patient should be scanned within 28 days prior to enrolment to rule out CNS metastases

5. Neoadjuvant/adjuvant chemotherapy within 6 months prior to enrolment

6. Radical radiotherapy with curative intent within 28 days prior to enrolment. Palliative radiotherapy for relief of bone pain not involving thoracic region is allowed prior to enrolment

7. Major surgery (including open biopsy), significant traumatic injury within 28 days prior to enrolment or anticipation of the need for major surgery during study treatment

8. Minor surgery, including insertion of an indwelling catheter, within 24 hours prior to the first bevacizumab infusion

9. Current or recent use of aspirin (>325 mg/day)

10. Current or recent (within 10 days of first dose of bevacizumab) use of full-dose oral or parenteral anticoagulants or thrombolytic agent for therapeutic purposes. Prophylactic use of anticoagulants is allowed

11. History of evidence of inherited bleeding diathesis or coagulopathy with the risk of bleeding

12. Uncontrolled hypertension (systolic >150 mmHg and/or diastolic >100 mmHg)

13. Clinically significant (i.e. active) cardiovascular disease for example CVA (=6 months before enrolment), myocardial infarction (=6 months before enrolment), unstable angina, CHF NYHA Class =II, serious cardiac arrhythmia requiring medication during the study and might interfere with regularity of the study treatment, or not controlled by medication

14. Non-healing wound, active peptic ulcer or bone fracture

15. History of abdominal fistula, gastrointestinal perforation or intra-abdominal abscess within 6 months of enrolment

16. Women with an intact uterus (unless amenorrhoeic for the last 24 months) not using effective, means of contraception (oral contraceptives in case not contraindicated for use with concomitant chemotherapy backbone treatment, intrauterine contraceptive device, barrier method of contraception in conjunction with spermicidal jelly or surgically sterile). Men who do not agree to use effective contraception during the study and for a period of 90 days following the last administration of bevacizumab

17. Treatment with any other investigational agent, or participation in another clinical trial within 28 days prior to enrolment

18. Known hypersensitivity to bevacizumab and any of its excipients, and any of the chemotherapies

19. Evidence of ongoing or active infection, any other disease, neurological or metabolic dysfunction, physical examination finding or laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or puts the patient at high risk for treatment-related complications.

20. Patients diagnosed with tracheo-oesophagela fistula

21. Prior chemotherpay or treatment with another system

Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Advanced or recurrent non-squamous non-small cell lung cancer
MedDRA version: 9 Level: PT Classification code 10059515

Intervention(s)

Trade Name: Avastin
Product Name: bevacizumab
Product Code: RO4876646
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: bevacizumab
CAS Number: 216974-75-3
Current Sponsor code: RO4876646
Other descriptive name: rhuMab, VEGF, anti-VEGF
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 100mg/4ml-

Trade Name: Avastin
Product Name: bevacizumab
Product Code: RO4876646
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: bevacizumab
CAS Number: 216974-75-3
Current Sponsor code: RO4876646
Other descriptive name: rhuMab, VEGF, anti-VEGF
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 400mg/16ml-

Primary Outcome(s)

Primary end point(s): The incidence of SAEs related to bevacizumab and the incidence of specific AEs (serious and non-serious) such as hypertension, proteinuria, wound healing complications, arterial and venous thomboembolic events, haemoptysis, CNS bleeding, other haemorrhages, gastrointestinal perforations and CHF, are considered as primary endpoints. (ECOG PS 2 patients will be analysed separately.)

Secondary Objective: To assess the efficacy of bevacizumab as measured by TTP and OS.
To assess the safety of bevacizumab in patients who develop CNS metastases during the treatment period.

Main Objective: To assess the safety profile of bevacizumab when combined with standard chemotherapy as first-line treatment of advanced or recurrent non-squamous NSCLC. In particular, the incidence of serious adverse events (SAEs) related to bevacizumab and the incidence of specific AEs (serious and non-serious) such as hypertension, proteinuria, wound healing complications, gastrointestinal perforations, arterial and venous thomboembolic events, haemoptysis, CNS bleeding, other haemorrhages and CHF will be investigated.

Secondary ID(s)

2005-005887-97-SI

MO19390