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Trial registered on ANZCTR


Registration number
ACTRN12609000980235
Ethics application status
Approved
Date submitted
11/11/2009
Date registered
13/11/2009
Date last updated
19/03/2013
Type of registration
Prospectively registered

Titles & IDs
Public title
The effect of RAD001 and Zoledronic acid in Renal cell cancer which has spread to the bones.
Scientific title
RAD001 and ZOledronic acid in Renal cell carcinoma patients with bone metastases (RAZOR) – a randomised phase II trial to evaluate the effect on control of bone metastases
Secondary ID [1] 1135 0
CTNZ 09_01
Universal Trial Number (UTN)
U1111-1112-4551
Trial acronym
RAZOR
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Renal Cell Carcinoma 252164 0
Bone metastases 252165 0
Condition category
Condition code
Cancer 252368 252368 0 0
Kidney
Cancer 252369 252369 0 0
Bone

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Participants will be treated with RAD001 and zoledronic acid. Participants are expected to ingest 10mg of RAD001 once a day. RAD001 comes in tablet form in 2.5mg, 5mg and 10mg strengths. Zoledronic acid (ZA) will be administered at a dose of 4mg by a 15 minute intravenous infusion (IV) once every 28 days. It is intended that patients continue on therapy, until one of the following criteria applies: a) Disease progression b) Intercurrent illness that prevents further administration of treatment c) Unacceptable adverse events(s) d) Patient decides to withdraw from the study e) General or specific changes in the patient's condition render the patient unacceptable for further treatment in the judgment of the investigator
Intervention code [1] 241533 0
Treatment: Drugs
Comparator / control treatment
Participants will be treated with RAD001. Participants are expected to ingest 10mg of RAD001 once a day. RAD001 comes in tablet form in 2.5mg, 5mg and 10mg strengths. It is intended that patients continue on therapy, until one of the following criteria applies: a) Disease progression b) Intercurrent illness that prevents further administration of treatment c) Unacceptable adverse events(s) d) Patient decides to withdraw from the study e) General or specific changes in the patient's condition render the patient unacceptable for further treatment in the judgment of the investigator
Control group
Active

Outcomes
Primary outcome [1] 253238 0
The primary objective is to assess the ability of RAD001 alone compared to the combination of RAD001 and ZA to control bone metastases from renal cell carcinoma by measuring the urinary N-telopeptide (uNTX) levels over a 12 week period.
Timepoint [1] 253238 0
uNTX will be measured at baseline, and on day one of weeks 1, 4, 8 and 12.
Secondary outcome [1] 262201 0
To assess the effects on plasma c-telopeptide (CTX)
Timepoint [1] 262201 0
CTX will be measured at baseline, and on day one of weeks, 1, 4, 8 and 12
Secondary outcome [2] 262202 0
To assess the effects on plasma CTX and correlate with uNTX
Timepoint [2] 262202 0
Plasma CTX and uNTX will be measured at baseline, and on day one of weeks, 1, 4, 8 and 12.
Secondary outcome [3] 262203 0
To assess the effects on bone pain and pain as measured by the Functional Assessment of Cancer Therapy - Bone Pain (FACT-BP) and Brief Pain Inventory (BPI) quality of life (QoL)questionnaires
Timepoint [3] 262203 0
Participants will be asked to complete (QoL) questionnaires at baseline, and on day one of weeks 4, 8 and 12.
Secondary outcome [4] 262204 0
To compare time to first skeletal related event (SRE). A SREs will be defined as the occurrence of a pathological fracture, spinal cord compression, requirement for radiation therapy, surgery to the bone or hypercalcemia of malignancy while on treatment or during follow-up.
Timepoint [4] 262204 0
Baseline and on day one of weeks 4, 8 and 12, and every 4 weeks thereafter until the end of treatment and then 12 weekly for a minimum of 1 year and a maximum of 3 years. It is intended that patients continue on therapy, until one of the following criteria applies: a) Disease progression b) Intercurrent illness that prevents further administration of treatment c) Unacceptable adverse events(s) d) Patient decides to withdraw from the study e) General or specific changes in the patient's condition render the patient unacceptable for further treatment in the judgment of the investigator
Secondary outcome [5] 297648 0
To compare progression free survival (PFS)
Timepoint [5] 297648 0
PFS is defined as the time from the date of randomization to the date of first documented progression or death due to any cause.
Secondary outcome [6] 297649 0
To compare tumour response
Timepoint [6] 297649 0
Tumour response to be assessed by CT scan according to RECIST 1.1 criteria at baseline, every 8 weeks until Week 40 and 12 weekly thereafter until disease progression or death or for a minimum of 1 year if on follow-up.

Eligibility
Key inclusion criteria
1. Patients must have histologically or cytologically confirmed renal cell carcinoma (RCC) 2. Patients must have evidence of at least one bone metastasis on imaging 3. Patients must not have received any prior therapy for advanced RCC. Prior radiotherapy is allowed, but must have been completed at least 4 weeks prior to randomisation. Prior systemic adjuvant therapy in a clinical trial is allowed. Prior bisphosphonates are allowed, but not within 4 weeks of study randomisation. Prior immunotherapy for advanced RCC is not allowed 4. Age >18 years 5. Life expectancy of greater than 3 months 6. Eastern Cooperative Oncology Group (ECOG) performance status <2 7. Patients must have normal organ and marrow function as defined as Haemoglobin >90 g/l, WBC >3.0 x109/L, Absolute Neutrophil Count > 1/5 x109/L, Platelets >100 x109/L, Bilirubin-within normal limits, ASL/ALT <2.5 ULN, Calcium 2.0-3.0 mmol/L, Creatinine Clearance >35 ml/min 8. Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation 9. Fasting serum cholesterol less than or equal to 7.75 mmol/L and fasting triglycerides less than or equal to 2.5 x upper limit of normal (ULN). In case one or both of these thresholds are exceeded, the patient can only be included after initiation of statin therapy and when the above mentioned values have been achieved 10. Ability to understand and the willingness to sign a written informed consent document
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Patients who have had radiotherapy or bisphosphonates within 4 weeks prior to entering the study 2. Patients may not be receiving any other investigational agents. 3. Patients with known brain metastases are excluded from this clinical trial unless they have undergone definitive treatment with either surgery or whole brain radiotherapy and been neurologically stable for > 6 weeks. Patients should either be off corticosteroids, or down to a low dose (less than or equal to 2mg dexamethasone or less than or equal to 10mg prednisone daily) and if still on corticosteroids, they must have normal glycaemic control. 4. History of allergic reactions attributed to compounds of similar chemical or biologic composition to RAD001 or zoledronic acid 5. Patients receiving any medications or substances that are potent inhibitors or inducers of CYP450 3A4 6. Uncontrolled intercurrent illness 7. Uncontrolled or brittle diabetes mellitus 8. Pregnant or breastfeeding women 9. Human Immunodeficiency Virus (HIV) -positive patients on combination antiretroviral therapy 10. Current active dental problems 11. Recent (within 6 weeks) or planned dental or jaw surgery 12. Prior organ transplantation on immunosuppressants 13. Patients with concurrent active second malignancy are ineligible 14. Patients who are HBsAg +ve AND who have not been commenced on appropriate HBV prophylaxis (e.g. lamivudine)

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)
Patients will be randomly allocated to RAD001 (Arm A) or RAD001 plus Zoledronic acid (Arm B) on a 1:1 ratio. Randomisation will be performed after completion of all baseline assessments via an office hours email/fax service via the Coordinating Trial Centre. Sites are required to complete Eligibility and Enrolment CRF pages to request randomisation.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
The randomisation sequence will be stratified and blocked by site. The sites are defined as either Auckland or other.
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint(s)
Safety/efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment outside Australia
Country [1] 2322 0
New Zealand
State/province [1] 2322 0

Funding & Sponsors
Funding source category [1] 244002 0
Commercial sector/Industry
Name [1] 244002 0
Novartis Pharmaceuticals Australia Pty Ltd
Address [1] 244002 0
54 Waterloo Road
North Ryde
NSW 2113
Country [1] 244002 0
Australia
Primary sponsor type
Commercial sector/Industry
Name
Uniservices
Address
Address and general enquiries:
UniServices House
70 Symonds Street
Auckland 1010

Postal Address:
c/- The University of Auckland
Private Bag 92019, Auckland Mail Centre
Auckland 1142,
Country
New Zealand
Secondary sponsor category [1] 251353 0
None
Name [1] 251353 0
Address [1] 251353 0
Country [1] 251353 0
Other collaborator category [1] 953 0
Other Collaborative groups
Name [1] 953 0
Cancer Trials New Zealand
Address [1] 953 0
Cancer Trials New Zealand
Discipline of Oncology
The University of Auckland
Private Bag 92019
Auckland 1142
Country [1] 953 0
New Zealand

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 244107 0
Multi Region Ethics Committee
Ethics committee address [1] 244107 0
Ethics committee country [1] 244107 0
New Zealand
Date submitted for ethics approval [1] 244107 0
16/11/2009
Approval date [1] 244107 0
14/01/2010
Ethics approval number [1] 244107 0
MEC/09/12/134

Summary
Brief summary
The main purpose of this study is to assess if RAD001 plus zoledronic acid, is a more effective treatment for patients with renal cell carcinoma and bone metastases compared to RAD001 alone.
Participants will be allocated to one of these two treatments with equal chances of each treatment being the one received.
Patients’ must have previously untreated advanced renal cell carcinoma, with at least one measurable bone metastases. Patients must be aged 18 years or older.
Zoledronic acid will be given as an intravenous venous (IV) infusion over 15 minutes once every 28 days. RAD001 will be taken by mouth, in tablet form, 10 mg every day.
Participants will undergo tests (medical history, physical examinations, blood & urine tests, electrocardiograms (ECG), a dental examination and Computerised Tomography (CT) scan to confirm they can enter the study.
Patients will be assessed every 28 days and have similar tests to monitor progress and identify and treat any side effects.
After the 12 week bone specific assessment period, subjects continue on therapy, on the treatment arm to which they are allocated, until one of the following criteria applies:
a) Disease progression
b) Intercurrent illness that prevents further administration of treatment
c) Unacceptable adverse events(s)
d ) Patient decides to withdraw from the study
e) General or specific changes in the patient's condition render the patient unacceptable for further treatment in the judgment of the investigator.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 30492 0
Dr Dr Reuben Broom
Address 30492 0
Medical Oncologist Building 7, Auckland City Hospital, Park Rd., Grafton, Auckland 1023
Country 30492 0
New Zealand
Phone 30492 0
+64 (0)9 307 4949
Fax 30492 0
Email 30492 0
reubenb@adhb.govt.nz
Contact person for public queries
Name 13739 0
Dr Dr Reuben Broom
Address 13739 0
Medical Oncologist
Building 7,
Auckland City Hospital,
Park Rd., Grafton,
Auckland 1023
Country 13739 0
New Zealand
Phone 13739 0
+64 (0)9 307 4949
Fax 13739 0
Email 13739 0
reubenb@adhb.govt.nz
Contact person for scientific queries
Name 4667 0
Dr Dr Reuben Broom
Address 4667 0
Medical Oncologist
Building 7,
Auckland City Hospital,
Park Rd., Grafton,
Auckland 1023
Country 4667 0
New Zealand
Phone 4667 0
+64 (0)9 307 4949
Fax 4667 0
Email 4667 0
reubenb@adhb.govt.nz

No information has been provided regarding IPD availability
Summary results
Have study results been published in a peer-reviewed journal?
Other publications
Have study results been made publicly available in another format?
Results – basic reporting
Results – plain English summary