Locally advanced or metastatic renal cell carcinoma MedDRA version: 20.0 Level: LLT Classification code 10038407 Term: Renal cell cancer System Organ Class: 100000004864
Conditions
Interventions
Trade Name: Votrient
Product Name: Votrient
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: PAZOPANIB
CAS Number: 444731-52-6
Concentration unit: mg milligram(s)
Concentration type: equal
Sponsors
iOMEDICO AG
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Histologically confirmed metastatic or locally advanced (defined as non operable tumor), predominantly clear cell renal cell carcinoma. 2. At least three of the following six predictors of short survival are required: o LDH > 1.5 x ULN o Hemoglobin 10 mg/dl (2.5 mmol/l) o time from initial diagnosis of renal-cell carcinoma to occurrence of metastases of less than 1 year o Karnofsky Status of 60 or 70 3. Karnofsky Status = 60 4. Age = 18 years or legal age of consent if greater than 18 years 5. Dated and signed written informed consent prior to performance of study-specific procedures or assessments 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 44 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 44
Exclusion criteria
Exclusion criteria: - Other malignancy. (Patients who have undergone prior radical or partial nephrectomy for RCC are allowed). Subjects who have had another malignancy and have been disease-free for five years, or subjects with a history of completely resected non-melanomatous skin carcinoma or successfully treated in situ carcinoma are eligible. - Prior systemic treatment for renal cell carcinoma. (NB: all treatments, neo-adjuvant, adjuvant or for locally advanced or metastatic RCC are not permitted.) - History or clinical evidence of central nervous system (CNS) metastases or leptomeningeal carcinomatosis, except for individuals who have previously-treated CNS metastases, are asymptomatic, and have had no requirement for steroids or anti-seizure medication for 6 months prior to first dose of study drug. Screening with CNS imaging studies (computed tomography (CT) or magnetic resonance imaging (MRI) is required only if clinically indicated or if the subject has a history of CNS metastases. - Clinically significant gastrointestinal abnormalities that may increase the risk for gastrointestinal bleeding including, but not limited to: o Active peptic ulcer disease o Known intraluminal metastatic lesion/s with risk of bleeding o Inflammatory bowel disease (e.g. ulcerative colitis, Chrohn’s disease), or other gastrointestinal conditions with increased risk of perforation o History of abdominal fistula, gastrointestinal perforation, or intra abdominal abscess within 28 days prior to beginning study treatment - History of any one or more of the following cardiovascular conditions within the past 6 months: o Myocardial infarction o Cardiac angioplasty or stenting o Unstable angina o Coronary artery bypass graft surgery o Symptomatic peripheral vascular disease o Class III or IV congestive heart failure, as defined by the New York Heart Association (NYHA) - Poorly controlled hypertension (defined as systolic blood pressure (SBP) of =140 mmHg or diastolic blood pressure (DBP) of = 90mmHg). Note: Initiation or adjustment of antihypertensive medication(s) is permitted prior to study entry. BP must be re-assessed on two occasions at intervals of at least one hour if it is not <140/90 mmHg at baseline assesment. On each of these occasions, SBP / DBP values from each BP assessment must be <140/90 mmHg in order for a subject to be eligible for the study - Pregnant or breast-feeding women - Known hypersensitive reaction to any of the components of study treatments
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Primary analysis will focus on the rate of poor risk patients as defined by the MSKCC criteria who are free of disease progression at 6 months after start of first line treatment with pazopanib. ;Secondary Objective: - Estimate the progression free survival of patients treated with pazopanib - To assess overall survival of poor risk patients treated with pazopanib. - To assess the overall response rate (ORR) according to RECIST-criteria 1.1 and the duration of response - To assess the safety profile of pazopanib in first line poor risk patients ;Primary end point(s): Rate of poor risk patients as defined by the MSKCC criteria who are free of disease progression at 6 months after start of first line treatment with pazopanib. ;Timepoint(s) of evaluation of this end point: 6 months (26 weeks) | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • To assess overall survival (OS) of poor risk patients treated with pazopanib. • To assess the safety profile of pazopanib in first line poor risk patients • To assess progression free survival (PFS) of patients treated with pazopanib • To assess overall response (ORR) rate and duration of response (DR) according to RECIST 1.1 Explorative analysis (Biomarker): • Relation between biomarkers and clinical outcome (response, stable disease, progression of disease) Explorative analysis (DCE-MRI): • To assess the overall response rate (ORR) according to RECIST-criteria 1.1 and the duration of response to first line therapy with pazopanib • To assess early clinical effects of therapy with pazopanib starting from 7 days compared with 2 months after first dose. • To assess the functional effects of therapy with pazopanib, e.g. vascularization of the tumor including morphological changes according to RECIST 1.1 • To assess the relationship of baseline parameters, early and late therapy effects with clinical outcome (overall and progression free survival) ;Timepoint(s) of evaluation of this end point: OS: date of death Safety profile: continuosly PFS: Day 1 of 9th and 17th week, after 6 months (26 weeks), after 32 weeks; after that period every 8 weeks until end of therapy ORR/DR: Day 1 of 9th and 17th week, after 6 months (26 weeks), after 32 weeks; after that period every 8 weeks until end of therapy Explorative Analyses: At Baseline, 2 weeks after start of therapy, on first day of cycles 2, 3, 5 and 7 and at end of therapy MRI substudy: Day 1, day 8 and week 8 of treatment | — |
Countries
Germany
Contacts
Public ContactiOMEDICO AG
iOMEDICO AG
Outcome results
None listed