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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT01249521




Registration number
NCT01249521
Ethics application status
Date submitted
29/11/2010
Date registered
30/11/2010
Date last updated
30/11/2010

Titles & IDs
Public title
Dual Targeting of Vascular Endothelial Growth Factor-A Together With Angiopoietins in Chemotherapy-naïve Metastatic Colorectal Cancer
Scientific title
Open Label Phase II Study Evaluating the Combination of Bevacizumab and AMG386 Without Chemotherapy as First Line Treatment of Advanced Colorectal Cancer
Secondary ID [1] 0 0
03501
Universal Trial Number (UTN)
Trial acronym
Vengeance
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Metastatic Colorectal Cancer 0 0
Condition category
Condition code
Cancer 0 0 0 0
Bowel - Back passage (rectum) or large bowel (colon)

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - AMG386 and bevacizumab

Treatment: Drugs: AMG386 and bevacizumab
AMG386 10mg/kg qw iv Bevacizumab 7.5mg/kg q3w iv
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Disease control (ie non progression) at 6 months
Timepoint [1] 0 0
6 months
Secondary outcome [1] 0 0
Toxicity
Timepoint [1] 0 0
weekly
Secondary outcome [2] 0 0
Overall survival
Timepoint [2] 0 0
3 monthly
Secondary outcome [3] 0 0
Response rate
Timepoint [3] 0 0
6 weeks

Eligibility
Key inclusion criteria
i) Histological diagnosis of colorectal cancer ii) Metastatic disease that is not resectable iii) Age > 18 years iv) Any patient in whom the investigator considers immediate cytotoxic chemotherapy is not required.

v) Measurable and/or non-measurable disease as assessed by CT scan vi) ECOG performance status 0, 1 or 2. vii) No prior chemotherapy except for adjuvant chemotherapy. viii) Adequate bone marrow function with platelets > 100 X 109/l; neutrophils > 1.5 X 109/l ix) Adequate renal function, with calculated creatinine clearance >40 ml/min (Cockcroft and Gault).

x) Adequate hepatic function with serum total bilirubin < 1.5 X upper limit of normal range xi) Life expectancy of at least 12 weeks xii) No other concurrent uncontrolled medical conditions xiii) No other malignant disease apart from non-melanotic skin cancer or carcinoma in situ of the uterine cervix or any other cancer treated with curative intent >2 years previously without evidence of relapse xiv) Women and partners of women of childbearing potential must agree to use adequate contraception xv) Written informed consent including consent for biomarker studies
Minimum age
No limit
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
i) Medical or psychiatric conditions that compromise the patient's ability to give informed consent or to complete the protocol ii) Uncontrolled hypertension iii) Prior treatment with VEGF inhibitors or angiopoietin inhibitors iv) Active bleeding disorders within the last 6 months v) Participation in any investigational drug study within the previous 4 weeks vi) Patients with uncontrolled clinically significant cardiac disease, arrhythmias or angina pectoris vii) Patients with a history of arterial or venous thrombosis within the last 12 months viii) Concurrent or prior (within 1 week before enrollment) anticoagulation therapy. The concurrent use of low molecular weight heparin or low dose warfarin (ie, 1 mg daily) for prophylaxis against thrombosis is acceptable while on study ix) Regular use of aspirin (>325mg/day) or NSAIDs (low dose aspirin (<325 mg/d), or occasional use of NSAIDs is acceptable) x) Treatment with immune modulators such as cyclosporine or tacrolimus within the previous 4 weeks xi) CNS metastases xii) Major surgical procedure within the last 28 days xiii) Minor surgical procedure, placement of access device, or fine needle aspiration within the last 7 days xiv) Serious non-healing wound, ulcer or bone fracture xv) 24 hour urinary protein > 1g/ 24 hours ( performed if urine dipstick > 1+ ) xvi) Pregnancy or lactation

Study design
Purpose of the study
Treatment
Allocation to intervention
NA
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
UNKNOWN
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
1/11/2010
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
1/11/2012
Actual
Sample size
Target
40
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 0 0
Austin Health - Melbourne
Recruitment postcode(s) [1] 0 0
3084 - Melbourne

Funding & Sponsors
Primary sponsor type
Government body
Name
Austin Health
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
This is a clinical trial investigating the effectiveness and safety of the combination of the study drugs bevacizumab and AMG386 in patients with advanced (metastatic) chemotherapy-naive bowel (colorectal) cancer. Chemotherapy has a significant impact in metastatic bowel cancer in terms of maintenance of quality of life and extension of survival. However, ultimately tumours will develop resistance to these agents and further treatment options are urgently required.

Angiogenesis is a process that results in the formation of new blood vessels. Similar to normal tissues, solid tumours require new blood vessels for growth and survival. Hence, drugs targeting angiogenesis may be useful treatment options for patients with bowel cancer.

AMG386 and bevacizumab act on 2 different pathways relevant to angiogenesis. There is evidence from laboratory and animal studies to suggest that such a combination could be useful as a cancer treatment. Previous studies in humans have shown that AMG386 and bevacizumab can be combined safely.. This study aims to evaluate the effectiveness and safety of the combination of AMG386 and bevacizumab in patients with advanced bowel cancer.

40 patients from approximately four hospitals in Australia will participate in this trial, with approximately 20 patients being enrolled at Austin Health. All participants will receive the same treatment.
Trial website
https://clinicaltrials.gov/study/NCT01249521
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Niall Tebbutt
Address 0 0
Austin Health
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Effie Skrinos
Address 0 0
Country 0 0
Phone 0 0
+61394963576
Fax 0 0
Email 0 0
[email protected]
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT01249521