A Randomised Phase II Study Evaluating Cediranib vs. Cediranib and Saracatanib in patients with relapsed metastatic clear cell renal cancer - COSAK

Active, not recruiting

• Conditions: Clear Cell Renal Cancer

• Registration Number: EUCTR2009-018014-20-GB
• Lead Sponsor: Common Services Agency

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2010-03-18
• Last Update Posted: 4 August 2015

Recruitment & Eligibility

• Status: Not Recruiting
• Sex: All
• Target Recruitment: 130

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.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

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 interven

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified