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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/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
N/A
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 status
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
Other
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/ct2/show/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/ct2/show/NCT01249521