E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Locally advanced or metastatic renal clear cell adenocarcinoma
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MedDRA Classification |
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
Primary efficacy objective: To assess whether the addition of TroVax® to first line standard of care, will prolong survival of patients with locally advanced or metastatic clear cell renal adenocarcinoma when compared to placebo. Analysis will occur after a predetermined number of deaths have occurred necessary to trigger the primary endpoint analysis or when specified by an independent Data Safety Monitoring Board based on analyses of interim data. The analysis will be based on the Intent to Treat (ITT) population, composed of all patients. Primary safety objective: To assess whether the addition of TroVax® to first line standard of care alters the profile of serious and non-serious adverse events, when compared to placebo, in patients with locally advanced or metastatic clear cell renal adenocarcinoma. This will be assessed in the Intent to Treat (ITT) population.
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E.2.2 | Secondary objectives of the trial |
Secondary efficacy objectives: •To compare the proportion of patients with progression free survival at 26 wks (+/- 1 week) in the TroVax® versus placebo arms based on radiological data. Data will be analysed using the ITT population and adjudicated (blinded peer review) baseline and week 26 radiological data. •To compare the tumour response rates, time to response and duration of response between patients treated with TroVax® versus placebo. This will be analysed in the ITT population. •To assess whether the addition of a minimum of three doses of TroVax® to first line standard of care, will prolong survival of patients with locally advanced or metastatic clear cell renal adenocarcinoma when compared to placebo. This will be an exploratory analysis in the Modified ITT population. •To assess whether TroVax® has an impact on the quality of life as measured by QLQ30 and EuroQOL questionnaires when compared to placebo. This will be analysed in the ITT population.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Signed informed consent. The patient must be competent to give written informed consent and comply with the protocol requirements. 2. Locally advanced or metastatic, histologically proven clear cell renal carcinoma. 3. Primary tumour surgically removed (some residual advanced primary tumour may remain). 4. At least four weeks post surgery or radiotherapy. 5. First-line. No prior therapy for renal cancer except surgery or radiotherapy. 6. Measurable disease. 7. Aged 18 years or more. 8. Patient expected to survive a minimum of 12 weeks (i.e. in the opinion of the investigator there is a >90% probability that the patient will survive >12 weeks if treated with the selected standard of care). 9. Free of clinically apparent autoimmune disease (including no prior confirmed diagnosis or treatment for autoimmune disease including Systemic Lupus Erythematosis, Grave’s disease, Hashimoto’s thyroiditis, multiple sclerosis, insulin dependant diabetes mellitus or systemic (non-joint) manifestations of rheumatoid disease). 10. Total white cell count ≥ 3 x 109/L and lymphocyte count ≥1 x 109/L. 11. Serum creatinine ≤1.5 times the upper limit of normal. 12. Bilirubin ≤ 2 times the upper limit of normal and an SGPT of ≤ 4 times the upper limit of normal. 13. Women must be either post menopausal, or rendered surgically sterile or, if of child bearing potential, must have been practising a reliable form of contraception (oral contraception + a barrier method) for at least three months prior to the first dose of TroVax® and must continue while they are being treated with TroVax®. Men must practise a reliable form of contraception (barrier or vasectomy) while they are being treated with TroVax®. 14. No acute changes on 12-lead ECG. 15. Ejection fraction documented as not less than 45% or no clinical suspicion that cardiac ejection fraction is less than 45%.(If clinical suspicion exists the ejection fraction should be measured according to local site procedures). 16. Karnofsky performance status of ≥ 80%. |
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E.4 | Principal exclusion criteria |
1. Cerebral metastases. (Known from previous investigations or clinically detectable). 2. Previous exposure to TroVax®. 3. Serious infections within the 28 days prior to entry to the trial. 4. Known to test positive for HIV or hepatitis B or C. 5. Life threatening illness unrelated to cancer. 6. History of allergic response to previous vaccinia vaccinations. 7. Known allergy to egg proteins. 8. Known hypersensitivity to neomycin. 9. Participation in any other clinical trial of a licensed or unlicensed drug within the previous 30 days or during the course of this trial. 10. Previous malignancies within the last 10 years other than successfully treated squamous carcinoma of the skin or in situ carcinoma of the cervix treated with cone biopsy. 11. Previous history of major psychiatric disorder requiring hospitalization or any current psychiatric disorder that would impede the patient's ability to provide informed consent or to comply with the protocol. 12. Oral corticosteroid use unless prescribed as replacement therapy in the case of adrenal insufficiency. 13. Ongoing use of agents listed in locally approved prescribing information as causing immunosuppression. 14. Prior history of organ transplantation. 15. Pregnancy or lactation. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Primary efficacy endpoint: The survival event rate ratio in the TroVax® arm versus the placebo in the Intent to Treat (ITT) population based on the log of the hazard ratio derived from the Cox Proportional Hazards regression model. A frequentist monitoring approach will be used for evaluating the event ratio. The key objective of this study is to determine whether TroVax® is able to prolong survival in patients receiving first line standard of care. Analysis is triggered by a predetermined number of deaths in the study population or when specified by an independent Data Safety Monitoring Board based on analyses of interim data. Primary safety endpoints: •The number of adverse events (serious and non-serious) in the Intent to Treat population in the TroVax® versus the placebo arm. •The laboratory variables (complete blood count and chemistry panel) in the Intent to Treat (ITT) population in the TroVax® versus the placebo arm.
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 4 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 30 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
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E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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This is a survival trial, so patients are followed-up until they die. |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 3 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 6 |