None listed
Conditions
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.
Interventions
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
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
Sponsors
Uniservices
Study design
Allocation
Randomised controlled trial
Intervention model
Parallel
Primary purpose
Treatment
Masking
Open (masking not used)
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Healthy volunteers
No
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
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)
Outcome results
None listed