Advanced or metastatic clear cell renal cancer. MedDRA version: 16.1 Level: LLT Classification code 10038416 Term: Renal clear cell carcinoma System Organ Class: 100000004864 MedDRA version: 16.1 Level: LLT Classification code 10009251 Term: Clear cell carcinoma of the kidney System Organ Class: 100000004864 MedDRA version: 16.1 Level: LLT Classification code 10023400 Term: Kidney cancer System Organ Class: 100000004864
Conditions
Interventions
Trade Name: Afinitor
Product Name: Everolimus
Pharmaceutical Form: Tablet
INN or Proposed INN: everolimus
CAS Number: 159351-69-6
Current Sponsor code: everolimus
Other descriptive name: EVEROLIMUS
Co
Sponsors
Werkgroep Immunotherapie Nederland voor Oncologie
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: - Subjects must provide written informed consent prior to performance of study-specific procedures or assessments, and must be willing to comply with treatment and follow-up. - Age = 18 years. - Histologically confirmed diagnosis of progressive metastatic clear cell renal cell cancer defined as >10% of the tumor cells having the clear cell phenotype. - Locally advanced (defined as disease not amenable to curative surgery or radiation therapy) or metastatic RCC (equivalent to Stage IV RCC according to AJCC staging - Eastern Cooperative Oncology Group (ECOG) performance status of 0-2. - Measurable disease. - No prior systemic anti-cancer treatment against clear cell renal cell cancer. - Adequate organ system function. - Non-childbearing potential. 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 50 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 50
Exclusion criteria
Exclusion criteria: - Prior malignancy. - History or clinical evidence of central nervous system (CNS) metastases or leptomeningeal carcinomatosis. - Clinically significant gastrointestinal abnormalities that may increase the risk for gastrointestinal bleeding including, but not limited to: 1)Active peptic ulcer disease. 2)Known intraluminal metastatic lesions with risk of bleeding. 3) Inflammatory bowel disease (e.g. ulcerative colitis, Crohn’s disease), or other gastrointestinal conditions with increased risk of perforation. 4)History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 28 days prior to beginning study treatment. -Clinically significant gastrointestinal abnormalities that may affect absorption of investigational product including, but not limited to: 1)Malabsorption syndrome. 2)Major resection of the stomach or small bowel. -Presence of uncontrolled infection. -Known past or present infection with Hepatitis B virus (HBV), Hepatitis C virus (HCV) or Human Immunodeficiency Virus (HIV). -Corrected QT interval (QTc) > 480 msecs using Bazett’s formula. -History of one or more of the following cardiovascular conditions within the past 6 months: 1)Cardiac angioplasty or stenting 2)Myocardial infarction 3)Stable or unstable angina pectoris. 4)Coronary artery bypass graft surgery. 5)Symptomatic peripheral vascular disease 6)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 =160 mmHg or diastolic blood pressure (DBP) of = 90mmHg]. - History of cerebrovascular accident including transient ischemic attack (TIA), pulmonary embolism or untreated deep venous thrombosis (DVT) within the past 6 months. - Prior major surgery or trauma within 28 days prior to first dose of study drug and/or presence of any non-healing wound, fracture, or ulcer (procedures such as catheter placement not considered to be major). - Evidence of active bleeding or bleeding diathesis. - Known endobronchial lesions and/or lesions infiltrating major pulmonary vessels. - Hemoptysis in excess of 2.5 mL (or one half teaspoon) within 8 weeks of first dose of study drug. - Any serious and/or unstable pre-existing medical, psychiatric, or other condition that could interfere with subject’s safety, provision of informed consent, or compliance to study procedures. - Unable or unwilling to discontinue use of prohibited medications or modify the dosing of interacting drugs as listed in Section 6.8.1. and 6.8.2 of the protocol for at least 14 days or five half-lives of a drug (whichever is longer) prior to the first dose of study drug and for the duration of the study. - Pregnant or lactating female. - Treatment with any of the following anti-cancer therapies: Radiation therapy, surgery or tumor embolization within 14 days prior to the first dose of Pazopanib OR Chemotherapy, immunotherapy, biologic therapy, investigational therapy or hormonal therapy.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective is to assess the progression-free survival of patients who receive bi-monthly rotations of Pazopanib and Everolimus versus patients who receive Pazopanib as a first line treatment. ;Primary end point(s): Progression-free survival;Timepoint(s) of evaluation of this end point: one year after randomization of the last subject;Secondary Objective: Time to second progression or death: defined as time to progressive disease per RECIST 1.1 on Everolimus monotherapy (when PD after 8 weeks Pazopanib) or on Pazopanib monotherapy (when PD after 8 weeks Everolimus) as second line treatment in arm A and time to progressive disease on Everolimus in arm B. Comparing time to 2nd PD with time to 2nd PD. Quality of life and toxicity. Quality of life assessments and Common Toxicity Criteria will be used. Overall survival Pharmacodynamic measurements and pharmacokinetic assessments at the switch of Pazopanib and Everolimus and vice versa. Genetic analysis of tumorbiopsies (optional). | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Time to second progression Quality of life Toxicity Overall survival Pharmacodynamic and pharmacokinetic assessments (optional) tumor biopsies for genetic profiling;Timepoint(s) of evaluation of this end point: Time to second progression, Quality of life, Toxicity, Overall survival: one year after randomization of the last subject Biomarkers: aim is within one year after randomization of last subject | — |
Countries
Netherlands
Contacts
Public ContactMedical oncology/G.A. Cirkel
UMC Utrecht
Outcome results
None listed