Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12606000507583
Ethics application status
Approved
Date submitted
24/11/2006
Date registered
7/12/2006
Date last updated
14/07/2016
Type of registration
Prospectively registered

Titles & IDs
Public title
ANZ 0601 / CIRG/TORI 010
Scientific title
A Randomized Phase 2 Trial of Double-Blind, Placebo Controlled AMG 706 in Combination with Paclitaxel, or Open-Label Bevacizumab in Combination with Paclitaxel, as First Line Therapy in Women with HER2 Negative Locally Recurrent or Metastatic Breast Cancer
Secondary ID [1] 321 0
Amgen Project Number: 20050225
Secondary ID [2] 287869 0
NCT00356681
Universal Trial Number (UTN)
Trial acronym
ANZ 0601 / CIRG/TORI 010
Linked study record

Health condition
Health condition(s) or problem(s) studied:
HER2 Negative Locally Recurrent or Metastatic Breast Cancer 1485 0
Condition category
Condition code
Cancer 1580 1580 0 0
Breast

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Eligible patients will be randomised in a 3-arm design to receive one of the following:

Arm B : Paclitaxel 90mg/m2 IV over 1 hour every week for 3 weeks (days 1, 8, 15, of each 28 day cycle) and blinded AMG 706 125mg orally every day.
Arm C : Paclitaxel 90mg/m2 IV over 1 hour every week for 3 weeks (days 1, 8, 15, of each 28 day cycle) and open label bevacizumab 10mg/kg IV following paclitaxel treatment on week 1 and week 3 of each cycle.

Treatment will be continued until disease progression, unacceptable toxicity or withdrawal of patient consent.
Intervention code [1] 1464 0
Treatment: Drugs
Comparator / control treatment
Arm A : Paclitaxel 90mg/m2 IV over 1 hour every week for 3 weeks (days 1, 8, 15, of each 28 day cycle) and blinded AMG 706 placebo 125mg orally every day.
Control group
Placebo

Outcomes
Primary outcome [1] 2183 0
To determine if treatment with paclitaxel and AMG 706 is superior to paclitaxel plus AMG 706 placebo in subjects with HER2 negative locally recurrent or metastatic breast cancer, based on objective response rates. Objective response rate is the percentage of patients assigned to a treatment arm with a confirmed best response of complete response or partial response as determined by an independent review committee.
Timepoint [1] 2183 0
The primary analysis for the objective response rate will be performed when all patients who are receiving protocol therapy have at least their second radiological image. An updated analysis will be performed when every patient on the study receiving protocol specified therapy have at least 10 months after first dose of study treatment.
Secondary outcome [1] 3809 0
• To estimate the differences in progression-free survival time, clinical benefit, overall survival and duration of response between Arm A (paclitaxel plus AMG 706 placebo) and Arm B (paclitaxel plus AMG 706).
Timepoint [1] 3809 0
For Arm A and Arm B.
Progression Free Survival: the interval from the date of randomization to the first documented date of disease progression or death. Patients who have not progressed or died while on study will be censored at their last evaluable assessment date.
Duration of response: the interval from date of initial documented response (complete response or partial response) to the first
documented date of disease progression or death if due to disease progression. Patients who responded and have not progressed while on study or died for reasons other than disease
progression will be censored at the date of assessment of the last CT scan.
Clinical benefit rate: the percentage of patients with a complete response, partial responses or stable disease lasting > 24 weeks.
Overall survival: the interval from the date of randomization and the date of death. Patients who have not died while on study drug will be censored at their last contact date.
Incidence of adverse events and laboratory abnormalities.
Secondary outcome [2] 3810 0
• To estimate the differences in objective response rate, progression-free survival time, clinical benefit, overall survival and duration of response between Arm B (paclitaxel plus AMG 706) and Arm C (paclitaxel plus bevacizumab).
Timepoint [2] 3810 0
For Arm B and Arm C.
Progression Free Survival: the interval from the date of randomization to the first documented date of disease progression or death. Patients who have not progressed or died while on study will be censored at their last evaluable assessment date.
Duration of response: the interval from date of initial documented response (complete response or partial response) to the first
documented date of disease progression or death if due to disease progression. Patients who responded and have not progressed while on study or died for reasons other than disease
progression will be censored at the date of assessment of the last CT scan.
Clinical benefit rate: the percentage of patients with a complete response, partial responses or stable disease lasting > 24 weeks.
Overall survival: the interval from the date of randomization and the date of death. Patients who have not died while on study drug will be censored at their last contact date.
Incidence of adverse events and laboratory abnormalities.
Secondary outcome [3] 3811 0
• To evaluate safety and tolerability in the three treatment arms.
Timepoint [3] 3811 0
The first Data Monitoring Committee review of safety data will occur no later than after the first 60 patients have been randomised and completed one cycle of therapy. The safety analysis will be conducted on all patients who received at least one dose of study drug post protocol amendment 1. Patients will be included in the analysis according to the treatment received. Safety evaluations will consist of medical interviews,
recording of adverse events, physical examinations, blood pressure, and laboratory measurements. Patients will be evaluated for adverse events at each study visit for the duration of their participation in the study. Hypertension will be monitored through routine evaluation of blood pressure.

Eligibility
Key inclusion criteria
Confirmed HER2 negative locally recurrent or metastatic breast cancer (locally recurrent disease must not be amenable to resection with curative intent); measurable disease per RECIST (Response Evaluation Criteria in Solid Tumor) guidelines; complete radiology and tumor measurement within 4 weeks (28 days) prior to randomization; ECOG Performance Status of 0 or 1; adequate organ and hematological function; negative pregnancy test within 7 days prior registration for patients of child-bearing potential and sexually active; written informed consent signed prior to any study-related procedures.
Minimum age
18 Years
Maximum age
Not stated
Sex
Females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Adjuvant or neoadjuvant taxane treatment within 12 months of randomization. Any other adjuvant chemotherapy regimen must be discontinued at least 3 weeks (21 days) prior to study randomisation.2. Prior chemotherapy for locally recurrent or metastatic breast cancer (prior endocrine therapyis permitted).3. Prior radiation therapy, radiofrequency ablation, percutaneous cryotherapy or hepaticchemoembolization on all sites of measurable disease unless disease progression was subsequently documented on at least one of these sites.4. Current or prior history of central nervous system metastasis.5. Common Terminology Criteria for Adverse Events (CTCAE) v 3.0 peripheral neuropathy > grade 2 at registration.6. Average systolic blood pressure > 145 mm Hg or average diastolic blood pressure > 85 mm Hg (average blood pressure of the 3 separate blood pressure values measured according to the Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure).7. History of arterial or venous thrombosis within 1 year prior to randomisation.8. History of bleeding diathesis or bleeding within 14 days of randomisation.9. Major surgical procedure within 4 weeks (28 days) prior to randomisation.10. Minor surgical procedure, placement of access device, or fine needle aspiration within 7 days of randomisation.11. Known positive test for human immunodeficiency virus (HIV), hepatitis C, or malignancy (other than in situ cervical cancer, or basal cell cancer of the skin), unless treated with curative intent and without evidence of disease for = 3 years before study randomisation.12. Clinically significant cardiac disease within 12 months of study randomisation, including myocardial infarction, unstable angina, grade II or greater peripheral vascular disease, cerebrovascular accident, transient ischemic attack, congestive heart failure, or ongoing arrhythmias requiring medication or pacemaker.13. Non-healing wound, ulcer or fracture.14. Ongoing or active infection.15. Positive hepatitis B surface antigen.16. Known chronic hepatitis.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Australian and New Zealand institutions will register and randomise patients in liaison with the Cancer International Research Group (CIRG) Office in Paris. At the time of study entry all participants will be allocated a treatment code via a web-based randomization system and blinded study drug (AMG 706) and open label study drugs will be supplied in accordance with the treatment code.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Minimisation.
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
This is a double-blind study in which both the subjects and investigators (clinicians assessing the patients) are blinded to the treatment.
Phase
Phase 2
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
1/12/2006
Actual
11/09/2007
Date of last participant enrolment
Anticipated
Actual
4/07/2008
Date of last data collection
Anticipated
Actual
Sample size
Target
273
Accrual to date
Final
282
Recruitment in Australia
Recruitment state(s)

Funding & Sponsors
Funding source category [1] 1724 0
Self funded/Unfunded
Name [1] 1724 0
Australia and New Zealand Breast Cancer Trials Group
Country [1] 1724 0
Australia
Funding source category [2] 1725 0
Commercial sector/Industry
Name [2] 1725 0
Amgen Inc
Country [2] 1725 0
United States of America
Funding source category [3] 1726 0
Other Collaborative groups
Name [3] 1726 0
Cancer International Research Group
Country [3] 1726 0
Canada
Primary sponsor type
Commercial sector/Industry
Name
Amgen Inc.
Address
Amen, Inc. One Amgen Centre Drive Thousand Oaks, CA 91320-1799 USA
Country
United States of America
Secondary sponsor category [1] 1521 0
Other Collaborative groups
Name [1] 1521 0
Cancer International Research Group (CIRG)
Address [1] 1521 0
Cancer International Research Group
Suite 1100
9925-109 Street
Edmonton
Alberta T5K 2J8, Canada
Country [1] 1521 0
Canada

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 3181 0
Auckland Hospital
Ethics committee address [1] 3181 0
Ethics committee country [1] 3181 0
New Zealand
Date submitted for ethics approval [1] 3181 0
Approval date [1] 3181 0
Ethics approval number [1] 3181 0
Ethics committee name [2] 3182 0
Border Medical Oncology
Ethics committee address [2] 3182 0
Ethics committee country [2] 3182 0
Australia
Date submitted for ethics approval [2] 3182 0
Approval date [2] 3182 0
Ethics approval number [2] 3182 0
Ethics committee name [3] 3183 0
Christchurch Hospital
Ethics committee address [3] 3183 0
Ethics committee country [3] 3183 0
New Zealand
Date submitted for ethics approval [3] 3183 0
Approval date [3] 3183 0
Ethics approval number [3] 3183 0
Ethics committee name [4] 3184 0
Concord Repatriation General Hospital
Ethics committee address [4] 3184 0
Ethics committee country [4] 3184 0
Australia
Date submitted for ethics approval [4] 3184 0
Approval date [4] 3184 0
Ethics approval number [4] 3184 0
Ethics committee name [5] 3185 0
Mater Sydney
Ethics committee address [5] 3185 0
Ethics committee country [5] 3185 0
Australia
Date submitted for ethics approval [5] 3185 0
Approval date [5] 3185 0
Ethics approval number [5] 3185 0
Ethics committee name [6] 3186 0
Princess Alexandra Hospital
Ethics committee address [6] 3186 0
Ethics committee country [6] 3186 0
Australia
Date submitted for ethics approval [6] 3186 0
Approval date [6] 3186 0
Ethics approval number [6] 3186 0
Ethics committee name [7] 3187 0
Royal Brisbane and Women's Hospital
Ethics committee address [7] 3187 0
Ethics committee country [7] 3187 0
Australia
Date submitted for ethics approval [7] 3187 0
Approval date [7] 3187 0
Ethics approval number [7] 3187 0
Ethics committee name [8] 3188 0
Royal Hobart Hospital
Ethics committee address [8] 3188 0
Ethics committee country [8] 3188 0
Australia
Date submitted for ethics approval [8] 3188 0
Approval date [8] 3188 0
01/06/2006
Ethics approval number [8] 3188 0
Ethics committee name [9] 3189 0
St Vincent's Hospital, Melbourne
Ethics committee address [9] 3189 0
Ethics committee country [9] 3189 0
Australia
Date submitted for ethics approval [9] 3189 0
Approval date [9] 3189 0
Ethics approval number [9] 3189 0
Ethics committee name [10] 3190 0
Tweed Hospital
Ethics committee address [10] 3190 0
Ethics committee country [10] 3190 0
Australia
Date submitted for ethics approval [10] 3190 0
Approval date [10] 3190 0
Ethics approval number [10] 3190 0
Ethics committee name [11] 3191 0
Waikato Hospital
Ethics committee address [11] 3191 0
Ethics committee country [11] 3191 0
New Zealand
Date submitted for ethics approval [11] 3191 0
Approval date [11] 3191 0
Ethics approval number [11] 3191 0

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 27398 0
Prof John F Forbes
Address 27398 0
ANZBCTG
PO Box 283
The Junction NSW 2291
Country 27398 0
Australia
Phone 27398 0
+61 2 4985 0113
Fax 27398 0
Email 27398 0
enquiries@anzbctg.org
Contact person for public queries
Name 10653 0
Corinna Beckmore
Address 10653 0
ANZBCTG
PO Box 283
The Junction NSW 2291
Country 10653 0
Australia
Phone 10653 0
+61 2 4925 3068
Fax 10653 0
+61 2 49850141
Email 10653 0
enquiries@anzbctg.org
Contact person for scientific queries
Name 1581 0
John F Forbes
Address 1581 0
ANZBCTG
PO Box 283
The Junction NSW 2291
Country 1581 0
Australia
Phone 1581 0
+61 2 4925 3068
Fax 1581 0
+61 2 49850141
Email 1581 0
enquiries@anzbctg.org

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No Supporting Document Provided



Results publications and other study-related documents

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