E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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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 |
The primary research objective is to see whether patients taking cediranib in combination with saracatanib have a longer progression free survival (surviving without their cancer returning or relapsing) than the patients who are taking cediranib with placebo. |
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E.2.2 | Secondary objectives of the trial |
Secondary objectives are: - to see if there are more side effects from taking cediranib and saracatanib compared to taking cediranib alone and to see how severe the side effects are - to compare overall survival length for both sets of patients - to test how well tumours respond to the drug treatment using Xray and CT scans of the cancer. - to test blood, cancer tissue and plasma samples for some patients to see if there is a biological 'marker' that indicates how well a patient might respond to cancer drugs and whether a patient is more likely to develop resistance to cancer drugs |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Histopathologically confirmed renal cell carcinoma with measurable metastases on CT/MRI imaging. - Radiological progressive disease on first line VEGF targeted therapy. First line VEGF targeted therapy must consist either pazopanib, sunitinib, sorafenib, bevacizumab. Patients treated with initial interferon prior to TKI exposure, or in combination with bevacizumab, are acceptable. - Evidence of measurable disease (ie, ≥1 malignant tumor mass that can be accurately measured in at least 1 dimension ≥ 20 mm with conventional computerized tomography [CT] scan or Magnetic Resonance Imaging [MRI], or ≥10 mm with spiral CT scan using a 5 mm or smaller contiguous reconstruction algorithm). Bone lesions, ascites, peritoneal carcinomatosis or miliary lesions, pleural or pericardial effusions, lymphangitis of the skin or lung, cystic lesions, or irradiated lesions are not considered measurable. - Adequate organ function as defined by the following criteria: - Total serum bilirubin ≤1.5 x ULN (patients with Gilbert’s disease exempt), - Serum transaminases <2.5 x ULN (x5 in the presence of liver metastasis - Serum creatinine ≤1.5 x ULN, - Absolute neutrophil count (ANC) ≥1000/mm3 without growth factor support, - Platelets ≥ 100,000/mm3 - Signed and dated informed consent document indicating that the patient (or legally acceptable representative) has been informed of all the pertinent aspects of the trial prior to enrolment. - Willingness and ability to comply with scheduled visits, treatment plans and laboratory tests and other study procedures - ECOG performance status of 0, 1 or 2. - Life expectance >12 weeks - At least 2 weeks since the end of prior systemic treatment (sunitinib, pazopanib, sorafenib) radiotherapy, or surgical procedure with resolution of all treatment-related toxicity to NCI CTCAE Version 3.0 grade ≤1 or back to baseline except for alopecia or hypothyroidism. A 4 week gap should exist since bevacizumanb +INF. |
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E.4 | Principal exclusion criteria |
- Congestive heart failure, myocardial infarction or coronary artery bypass graft in the previous six months, ongoing severe heart disease. - Pregnancy or breastfeeding. Patients must be surgically sterile or be postmenopausal, or must agree to use effective contraception during the period of therapy. The definition of effective contraception will be based on the judgment of the principal investigator or a designated associate. Male patients must be surgically sterile or agree to use effective contraception. - Other severe acute or chronic medical or psychiatric condition, or laboratory abnormally that would impart, in the judgment of the investigator, excess risk associated with study participation or study drug administration, or which, in the judgment of the investigator, would make the patient inappropriate for entry into this study - Untreated unstable brain or meningeal metastases or tumour. Patients with radiological evidence of stable brain metastases are eligible providing that they are asymptomatic and either do not require corticosteroids or have been treated with corticosteroids, with clinical and radiological evidence of stabilisation at least 10 days after discontinuation of steroids. - Greater than +1 proteinuria on two consecutive dipsticks taken no less than 1 week apart unless urinary protein < 1.5g in a 24 hr period or protein/creatinine ratio < 1.5. - History of significant gastrointestinal impairment, as judged by the investigator, that would significantly affect the absorption of cediranib - Patients with a recent history of poorly controlled hypertension with resting blood pressure >150/100 mmHg in the presence or absence of a stable regimen of anti-hypertensive therapy, or patients who are requiring maximal doses of calcium channel blockers to stabilize blood pressure - Any evidence of severe of uncontrolled diseases eg, unstable or uncompensated respiratory, hepatic or renal disease. - Mean QTc with Bazetts correction >480msec in screening ECG or history of familial long QT syndrome - Any evidence of interstitial lung disease (bilateral, diffuse, parenchymal lung disease). - Significant haemorrhage (>30mL bleeding/episode in previous 3 months) or haemoptysis (>5mL fresh blood in previous 4 weeks) - Recent (<14 days) major thoracic or abdominal surgery prior to entry into the study, or a surgical incision that is not fully healed - Unresolved toxicity ≥ CTC grade 2 (except alopecia) from previous anti-cancer therapy. - History of other malignancies (except for adequately treated basal or squamous cell carcinoma or carcinoma in situ or localised controlled prostate cancer) within 5 years, unless the patient has been disease free for 2 years and there is a tissue diagnosis of the primary cancer of interest from a target lesion. - Known inherited or acquired immunodeficiency - Known risk of the patient transmitting HIV, hepatitis B or C via infected blood - Involvement in the planning and conduct of the study - Previous enrolment or randomisation of treatment in the present study. - Treatment with an investigational (not including VEGF TKIs such as pazopanib) drug within 30 days prior to the first dose of cediranib. - Other concomitant anti-cancer therapy (including LHRH agonists) except steroids - Previous bone marrow transplant - Study drugs should be permanently discontinued in patients with the following conditions: - Gastrointestinal perforation or wound dehiscence requiring medical intervention - Serious haemorrhage, ie, requiring medical intervention - Severe hypertension (see hypertension management protocol) - Nephrotic syndrome - Severe arterial thromboembolic event |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary outcome measure is the length of time from the date of randomisation to the date of disease progression |
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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 | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
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) | Information not present in EudraCT |
E.7.1.1 | First administration to humans | Information not present in EudraCT |
E.7.1.2 | Bioequivalence study | Information not present in EudraCT |
E.7.1.3 | Other | Information not present in EudraCT |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | Information not present in EudraCT |
E.7.4 | Therapeutic use (Phase IV) | Information not present in EudraCT |
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 | No |
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) | Yes |
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 | 20 |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
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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The end of the trial will be the date when the last patient has completed their final follow up visit. |
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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 | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
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 | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |