Patients affected by untreated metastatic renal cell carcinoma with bone involvement MedDRA version: 21.0 Level: PT Classification code 10073251 Term: Clear cell renal cell carcinoma System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Trade Name: VOTRIENT - 200 MG -COMPRESSA RIVESTITA CON FILM -USO ORALE-FLACONE (HDPE) 30 COMPRESSE
Product Name: Votrient
Product Code: [Votrient]
Pharmaceutical Form: Film-coated tablet
INN or Prop
Sponsors
FONDAZIONE IRCCS "ISTITUTO NAZIONALE DEI TUMORI"
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: - Written informed consent - Age = 18 and = 80 years - ECOG Performance Status: 0-1-2 - Life expectancy =24 weeks - Diagnosis of predominantly clear cell RCC - Risk score (Heng criteria): favorable or intermediate - No previous systemic treatment for Renal Cell Carcinoma - Documented metastatic disease (CT scan or MRI) with at least two bone metastasis (non pretreated with radiotherapy). Lesions could be measurable or not according with RECIST criteria v.1.1. -Laboratory requirements: Neutrophils =1.5 x 109/L, Platelets =100 x 109/L, and Haemoglobin =10g/dL; Total bilirubin =1.5 time the upper-normal limits (UNL) of the Institutional normal values except for patients affected by Gilbert’s syndrome; AST (SGOT) and/or ALT (SGPT) =2.5 x UNL, or =5 x UNL in case of liver metastases; alkaline phosphatase =2.5 x UNL, =5 x UNL in case of liver metastases, =10 x UNL in case of bone metastases - Patients should be compliant to study protocol procedures - Patients could receive a bone targeted agents after the first two cycles of Pazopanib treatment; the preferred drug is denosumab (due to best renal safety) - Patients that will receive bone targeted agents must have baseline dental scan and dental examination (and after every 6 months) - Patients of childbearing age should use contraceptive methods during the study 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 61 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 27
Exclusion criteria
Exclusion criteria: - Previous systemic treatment for mRCC - Non-clear-cell histology - Poor prognosis as defined by Heng criteria - History of malabsorption syndrome - Pregnant or breastfeeding women - Concomitant cardiac disorders: cardiac failure NYHA> 2; Acute coronary syndrome or myocardial infarction or severe or unstable angina within the last 6 months as well as uncontrolled hypertension (= 160/90) - Uncontrolled diabetes - Patients with single bone lesion that could receive curative treatment (radiotherapy or surgery) - Known central nervous system (CNS) metastases other than stable, treated brain metastases. Subjects with previously treated brain metastasis will be allowed if the brain metastasis has been stable by neuroimaging for at least 3 months following prior treatment (radiotherapy or surgery) - Other cancer within the previous 5 years (except for in situ skin carcinoma, superficial bladder Ta, Tis, T1 and carcinoma of the cervix or every cancer with curative treatment within 5 years) - Known human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS)-related illness, or active hepatitis B or C - Surgery, chemotherapy, or other anti-cancer therapy within 4 weeks prior to enrollment in the study - Intravenous bisphosphonate or denosumab for bone metastasis, when started in the 3 months period before study inclusion - Planned radiation therapy or surgery to bone must be before 2 weeks to study enrollment - Radiotherapy during the study (except palliative radiotherapy) - Inability to swallow tablets or capsules
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the efficacy of first line therapy with Pazopanib, in terms of progression free survival (PFS), in patients with metastatic renal cell carcinoma with bone involvement;Secondary Objective: To assess the safety and tolerability of the first line treatment with Pazopanib. To evaluate pain and quality of life of patients, by means of specific questionnaries. Exploratory objectives: to study the effect of Pazopanib on bone turnover markers;Primary end point(s): Progression free survival (PFS);Timepoint(s) of evaluation of this end point: From the start of the first line treatment with Pazopanib until disease progression or death from any cause | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Study treatment safety and tolerability according to the NCI-CTCAE version 4.03 ; Incidence of Skeletal Related Events (SREs) ; Time to pain progression and pain response according to the Brief Pain Inventory–Short Form (BPI-SF) ; Quality of live according to the NCCN-FACT FKSI-19 and EORTC QLQ-C30 questionnaires; The exploratory objectives of this study are to evaluate the effects of Pazopanib on Bone turnover markers, as follows: 1) Total alkaline phosphatase (ALP) will be measured by standard automated analytical procedures. 2) Bone alkaline phosphatase (BAP) level will be measured by measured by precipitation with wheat germ lectin or electrophoresis-precipitation. 3) Serum ß-C-terminal telopeptide of type I collagen (CTx) will be measured by (ELISA) or radioimmunoassay (RIA). 4) Procollagen type I propeptides (PINP) (ELISA) 5) Tartrate-resistant acid phosphatase (TRAcP) (ELISA) 6) Osteoprotegerin (OPG) (ELISA) 7) Receptor activator of nuclear factor kappa-B ligand (RANKL) (ELISA) ;Timepoint(s) of evaluation of this end point: From the date of signature of informed consent until 30 days after the last dose of study drug ; During treatment period and follow-up; At baseline, at day 1 of each treatment cycle and at the end of the treatment (EOT visit) until the end of study period; At baseline, at day 1 of each treatment cycle and at the end of the treatment (EOT visit) until the end of study period; At baseline, month 2, first tumour radiological evaluation as per protocol and at disease progression | — |
Countries
Italy
Contacts
Public ContactServizio Informazione sulla Sperime
Fondazione Istituto Nazionale dei Tumori di Milano
Outcome results
None listed