Metastatic Renal Cell Carcinoma MedDRA version: 14.1 Level: PT Classification code 10050513 Term: Metastatic renal cell carcinoma System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Product Name: Sunitinib Malate
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: Sunitinib Malate
CAS Number: 557795-19-4
Concentr
Sponsors
Cambridge University Hospitals NHS Foundation Trust and University of Cambridge
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: • Presumed metastatic (Stage IV) renal cell carcinoma, as defined by the referring clinician • Clinically fit and scheduled for nephrectomy • No prior systemic therapy for renal cell carcinoma • Male or female, 18 years of age or older • Life expectancy of 12 weeks or greater • ECOG performance status 0 or 1 • Radiologically documented, RECIST measurable, metastatic disease. Measurable disease, defined by the presence of at least one lesion outside of the kidney which can be measured in at least one dimension with the longest diameter = 20mm using chest X-ray, = 10mm calliper measurement by clinical exam or = 10mm using spiral CT. • Laboratory parameters as follows: o Serum aspartate transaminase (AST) or serum alanine transaminase (ALT) =2.5 x upper limit of normal (ULN), or AST or ALT =5 x ULN if liver function abnormalities are due to underlying malignancy o Total serum bilirubin =1.5 x ULN o Absolute neutrophil count (ANC) =1.5 x 10^9/L o Platelets =100 x 10^9/L o Haemoglobin =90 g/L (However where a transfusion is scheduled the patient may have a lower a value but this must be discussed and approved) o Serum creatinine =1.5 x ULN o Prothrombin time (PT) =1.5 x ULN • Willingness and ability to comply with scheduled visits, treatment plans, laboratory tests, and other study procedures • Before patient registration, written informed consent, including for preoperative biopsy, must be given according to ICH/GCP, national and local regulations Are the trial subjects under 18? no Number of subjects for this age range: 0 F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 0 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 0
Exclusion criteria
Exclusion criteria: • Presence of = grade 3 (NCI CTCAE grading version 3.0) haemorrhage within 4 weeks of registration. • Any previous chemotherapy or investigational treatment given for renal carcinoma. • Diagnosis of any other malignancy within the last 5 years, except for adequately treated basal cell carcinoma, squamous cell skin cancer, or in situ cervical cancer • Any of the following within the 12 months prior to study drug administration: myocardial infarction, severe/unstable angina, coronary/peripheral artery bypass graft, symptomatic congestive heart failure, cerebrovascular accident or transient ischemic attack, or pulmonary embolism • Any major surgery in the previous 4 weeks. • Co-administration of CYP3A4 inducer or inhibitor medications that would require an increase or decrease in sunitinib dosage from the study dose of 50 mg o.d. • Pre-existing thyroid abnormality with thyroid function that cannot be maintained in the normal range with medication • Ongoing cardiac dysrhythmias of = grade 2 (NCI CTCAE grading version 3.0), atrial fibrillation of any grade, or prolongation of the QTc interval to >450 msec for males or >470 msec for females • Treatment with drugs of dysrhythmic potential is not allowed • Concurrent participation in another clinical trial using an investigational medicinal product • Known human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS)-related illness • Pregnancy or breastfeeding. • Female patients must be surgically sterile, be postmenopausal, or must agree to use effective contraception during the period of therapy and for 6 months after. All female patients with reproductive potential must have a negative pregnancy test (serum or urine) prior to enrolment. Male patients must be surgically sterile or must agree to use effective contraception during the period of therapy and for 6 months after. Barrier contraception is recommended. • Other severe acute or chronic medical or psychiatric condition, or laboratory abnormality that may increase the risk associated with study participation or study drug administration, or in the judgment of the investigator would make it undesirable for the patient to enter the trial. • Uncontrolled hypertension. Patients are excluded with current blood pressure of either systolic = 150 or diastolic =90. Patients using anti-hypertensive medication to control blood pressure to these levels are elgible.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To determine the anti-tumour activity of sunitinib when given before and after nephrectomy to previously untreated patients with metastatic renal cell carcinoma; Secondary Objective: To describe the toxic effects of sunitinib given before and after nephrectomy until disease progression to previously untreated patients with metastatic renal cell carcinoma To evaluate, pathologically, evidence of sunitinib activity in the primary RCC lesion To correlate pathological response with clinical response To identify in vivo targets for sunitinib in renal cell cancer by analysis of tumour samples prior to and during therapy To correlate changes in serum and tumour biomarkers with both response to treatment and toxicity To evaluate changes in diffusion weighted (DWI-MRI), BOLD and dynamic contrast enhanced magnetic resonance imaging (DCE MRI) of the tumour before and after 12 days of sunitinib therapy ;Primary end point(s): The primary endpoint of this study is objective response rate. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • Objective clinical benefit rate (by RECIST criteria) of sunitinib • Pathological response as measured by % tumour necrosis • Morbidity and mortality related to sunitinib intra-operatively and post-operatively e.g. risk of bleeding, thrombosis, delayed wound healing, sepsis • Time to hospital discharge post-nephrectomy • Response rate, overall survival, time to progression and response duration • Toxicity of sunitinib (by NCI CTCAE grading version 3.0) • Expression of all major VEGF isoforms, PDGFR, c-KIT and FLT-3 in tissue samples as measured by RT-PCR and Western blotting • VEGF-A and VEGF-C levels in serum as measured by ELISA • VHL, PTEN and RAS typing on tumour • To evaluate changes in diffusion weighted (DWI-MRI), BOLD and dynamic contrast enhanced magnetic resonance imaging (DCE MRI) of the tumour before and after 12 days of sunitinib therapy | — |
Countries
United Kingdom
Outcome results
None listed