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Trial registered on ANZCTR


Registration number
ACTRN12612000136808
Ethics application status
Approved
Date submitted
16/05/2011
Date registered
31/01/2012
Date last updated
31/01/2012
Type of registration
Retrospectively registered

Titles & IDs
Public title
Phase I study of RAD001 (Everolimus) in combination with Fluvastatin and Zoledronic acid in patients with solid tumours
Scientific title
A study of the safety and toxicity of the combination of zoledronic acid, fluvastatin and everolimus given to patients with advanced cancer
Secondary ID [1] 252970 0
Nil applicable
Universal Trial Number (UTN)
U1111-1117-6020
Trial acronym
Not applicable
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Advanced cancers 258495 0
Condition category
Condition code
Cancer 258665 258665 0 0
Any cancer

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Everolimus 2.5mg (dose level 1) to 5mg (dose level 2) to 10mg daily (dose level 3), fluvastatin 80mg (dose levels 1 &2) to 120mg daily (dose level 3) , and zoledronic acid 4mg (fixed dose) intravenously every 3 weeks.

After recruitment for each dose level has been completed (no set time), toxicity will be assessed for that dose level before patients are enrolled onto the next dose level.

Endpoint depends on toxicity during the first cycle.
Intervention code [1] 257493 0
Treatment: Drugs
Comparator / control treatment
Not applicable
Control group
Uncontrolled

Outcomes
Primary outcome [1] 259520 0
Toxicity and safety
Timepoint [1] 259520 0
Clinical assessments according to NCI Common Toxicity criteria to measure toxicity at any point in the first 3 weeks (1 cycle) of treatment
Secondary outcome [1] 266129 0
Pharmacokinetics of everolimus, fluvastatin and zoledronic acid (if possible)
Timepoint [1] 266129 0
Response rates, if there is measureable disease, will be assessed after 3 cycles (9 weeks) and 6 cycles (18 weeks) of treatment

Eligibility
Key inclusion criteria
Histologic or cytologic diagnosis of a solid tumour.
No curative treatment options available.
Evidence of locally advanced or metastatic disease. This can be measurable, evaluable, or nonmeasurable.
Up to three prior chemotherapy regimens for advanced disease is permitted.
No chemotherapy (hormonal therapy excluded) for at least 4 weeks before enrollment in study (6 weeks for mitomycin or nitrosoureas).
WHO Performance Status 0 - 2.
Estimated life expectancy of at least 12 weeks.
Prior radiation therapy is allowed provided no more than 30% of bone marrow producing areas have been irradiated and patients must have recovered from the acute toxic effects of the treatment prior to study enrollment. Radiation therapy must have been completed at least 2 weeks prior to commencing study treatment.
Prior bisphosphonate therapy is allowed, but any previous zoledronic acid must have been administered no more frequently than once a month. Prior HMGCoA reductase therapy for hypercholesterolemia is allowed, but patients should be willing to change to fluvastatin on trial.
Adequate organ function including the following:
Adequate bone marrow reserve: absolute neutrophil count (ANC) greater or less than 1.5 × 109/L, platelets greater or less than 100 × 109/L, hemoglobin greater or less than 9 g/dL.
Hepatic: bilirubin greater than 2 times upper limit of normal (× ULN), alkaline phosphatase (ALP), aspartate transaminase (AST), and alanine transaminase (ALT) greater than 3.0 × ULN (ALP, AST, and ALT greater than 5 × ULN is acceptable if liver has tumor involvement). NB, if LFTs meet the criteria for RAD001 dose reduction at study enrolment, the dose of RAD001 will be halved in the first instance.
Renal: serum creatinine greater than 0.16 mmol/l or creatinine clearance greater than 60ml / min
Signed informed consent.
Minimum age 18 years.
Patients on study with reproductive potential, or with female partners with reproductive potential, must use an effective contraceptive method during the trial and for 3 months after the study.
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1] Patients receiving another investigational drug
2] Active infection or chronic infection. This includes bacterial, as well as fungal and viral infections. Patients with HIV, Viral Hepatitis of any sort (including carriers) are excluded in view of the potential for immunosuppresion with RAD001
3] Uncontrolled brain metastases. Patients with meningeal metastases are eligible.
4] Pregnancy or breast-feeding.
5] Serious concomitant medical or psychiatric disorders which would compromise the safety of the patient or their ability to complete the study, at the discretion of the investigator.
6] Significant cardiovascular disease: unstable angina, myocardial infarction within 3 months or significant cardiac failure.
7] Patitents on medications potentially a substrate for CYP3A4 (see Appendix 3) are eligible if they are able to stop the relevant medication prior to study entry. However, patients unable to stop their medications (other than a HMGCoA reductase inhibitor) are ineligible. It is not known whether fluvastatin is a substrate for CYP3A4, so patients who are willing to change their HMGCoA reductase inhibitor to fluvastatin are eligible.

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
This is a Phase I non-randomised study, so patients do not undergo randomisation or concelment or blinding procedures. Patients are enrolled in the study in the order that they are consented.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Not applicable
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
This is a standard Phase I dose escalation study
Phase
Phase 1
Type of endpoint(s)
Safety
Statistical methods / analysis

Recruitment
Recruitment status
Active, not recruiting
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 in Australia
Recruitment state(s)
NSW

Funding & Sponsors
Funding source category [1] 257942 0
Commercial sector/Industry
Name [1] 257942 0
Novartis Pharmaceuticals Australia Pty Ltd
Address [1] 257942 0
Novartis Pharmaceuticals Australia Pty Limited
54 Waterloo Road
North Ryde NSW 2113
Country [1] 257942 0
Australia
Primary sponsor type
Hospital
Name
St George Hospital
Address
Gray Street
Kogarah
NSW 2217
Australia
Country
Australia
Secondary sponsor category [1] 257140 0
None
Name [1] 257140 0
Address [1] 257140 0
Country [1] 257140 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 259952 0
St George Hospital
Ethics committee address [1] 259952 0
Gray Street
Kogarah
NSW 2217
Ethics committee country [1] 259952 0
Australia
Date submitted for ethics approval [1] 259952 0
Approval date [1] 259952 0
14/12/2007
Ethics approval number [1] 259952 0

Summary
Brief summary
This study aims to investigate whether the combination of everolimus (RAD001), fluvastatin, and zoledronic acid can be given safely together and to determine the toxicities, if any, of the combination. Who is it for? You may be eligible for this study if you have advanced cancer which has continued to grow despite the use of other therapies. Trial Details In this trial, you will receive an combined treatment of the drugs Everolimus escalating from 2.5mg to 10mg daily, fluvastatin 80mg to 120mg daily, and zoledronic acid 4mg intravenously every 3 weeks until either you experience intolerable side effects or until your cancer grows again. We hope that the combination treatment will ultimately not only be fairly well tolerated, but act synergistically to help slow down the rate of tumour growth.
Trial website
Not applicable
Trial related presentations / publications
None as yet
Public notes

Contacts
Principal investigator
Name 31839 0
Address 31839 0
Country 31839 0
Phone 31839 0
Fax 31839 0
Email 31839 0
Contact person for public queries
Name 15086 0
Antoinette Fontela
Address 15086 0
Cancer Care Centre
St George Hospital
Gray Street, Kogarah
NSW, 2217
Country 15086 0
Australia
Phone 15086 0
+612 9113 3910
Fax 15086 0
+612 9113 3958
Email 15086 0
Antoinette.Fontela@SESIAHS.HEALTH.NSW.GOV.AU
Contact person for scientific queries
Name 6014 0
Paul de Souza
Address 6014 0
Cancer Care Centre
St George Hospital
Gray Street, Kogarah
NSW, 2217
Country 6014 0
Australia
Phone 6014 0
+612 9113 3910
Fax 6014 0
+612 9113 3958
Email 6014 0
p.desouza@unsw.edu.au

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