Advanced Renal Cell Carcinoma MedDRA version: 12.0 Level: LLT Classification code 10038410 Term: Renal cell carcinoma recurrent MedDRA version: 12.0 Level: LLT Classification code 10050513 Term: Metastatic renal cell carcinoma
Conditions
Interventions
Product Name: AV-951
Product Code: Tivozanib
Pharmaceutical Form: Capsule*
CAS Number: 682745-41-1
Current Sponsor code: Tivozanib (AV-951)
Other descriptive name: KRN951
Concentration unit: mg millig
Sponsors
AVEO Pharmaceuticals, Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. = 18-years of age. 2. Subjects with recurrent or metastatic RCC. 3. Subjects must have undergone prior nephrectomy (complete or partial) for excision of the primary tumor. 4. Histologically or cytologically confirmed RCC with a clear cell component (subjects with pure papillary cell tumor or other non-clear cell histologies, including collecting duct, medullary, chromophobe, mixed tumor containing predominantly sarcomatoid cells, and unclassified RCC are excluded). 5. Measurable disease per the RECIST criteria Version 1.0 (see Appendix A). Measurable disease must be verified by an independent radiologist prior to randomization. 6. Treatment naïve subjects or subjects who have received no more than one prior systemic treatment (immunotherapy, including interferon-alfa or interleukin-2 based therapy, chemotherapy, hormonal therapy or an investigational agent) for metastatic RCC. Postoperative or adjuvant systemic therapy will not be counted as a prior therapy unless recurrence is detected within 6 months of completion of treatment, in which case it will be counted as a prior therapy for metastatic disease. 7. ECOG performance status of 0 or 1, and life expectancy = 3 months (see Appendix B). 8. If female and of childbearing potential, documentation of negative pregnancy test prior to enrollment. 9. Ability to give written informed consent and comply with protocol requirements. 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
Exclusion criteria: 1. Any prior VEGF-directed therapy including VEGF antibody (eg, bevacizumab), VEGF receptor tyrosine kinase inhibitor (eg, sunitinib, sorafenib, axitinib, pazopanib, etc.), VEGF trap (eg, aflibercept), or any other agent or investigational agent targeting the VEGF pathway. 2. Any prior therapy with an agent targeting the mTOR pathway (eg, temsirolimus, everolimus, etc) 3. Primary CNS malignancies or symptomatic CNS metastases; subjects with previously treated brain metastasis will be allowed if the brain metastasis have been stable without steroid treatment for at least 3 months following prior treatment (radiotherapy or surgery). 4. Any listed hematologic abnormalities 5. Any listed serum chemistry abnormalities 6. Significant cardiovascular disease 7. Non-healing wound, bone fracture, or skin ulcer. 8. Active peptic ulcer disease, inflammatory bowel disease, ulcerative colitis, or other gastrointestinal condition with increased risk of perforation; history of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 4 weeks prior to administration of first dose of study drug 9. Serious/active infection or infection requiring parenteral antibiotics. 10. Inadequate recovery from any prior surgical procedure or major surgical procedure within 4 weeks prior to administration of first dose of study drug. 11. Significant thromboembolic or vascular disorders within 6 months prior to administration of first dose of study drug, including but not limited to: Deep vein thrombosis Pulmonary embolism Cerebrovascular accident (CVA) or transient ischemic attach (TIA) Peripheral arterial ischemia > Grade 2 Coronary or peripheral artery bypass graft. 12. Significant bleeding disorders within 6 months prior to administration of first dose of study drug, including but not limited to. Hematemesis, hematochezia, melena or other gastrointestinal bleeding Grade =2 Hemoptysis or other pulmonary bleeding Grade =2 Hematuria or other genitourinary bleeding Grade =2 13. Currently active second primary malignancy, including hematologic malignancies (leukemia, lymphoma, multiple myeloma, etc.), other than non-melanoma skin cancers, non-metastatic prostate cancer, in situ cervical cancer and ductal or lobular carcinoma in situ of the breast. Subjects are not considered to have a currently active malignancy if they have completed anti-cancer therapy and have been disease free for >2 years. 14. Pregnant or lactating females. 15. History of genetic or acquired immune suppression disease such as HIV; subjects on immune suppressive therapy for organ transplant. 16. Life-threatening illness or organ system dysfunction compromising safety evaluation. 17. Requirement for hemodialysis or peritoneal dialysis. 18. Inability to swallow pills, malabsorption syndrome or gastrointestinal disease that severely affects the absorption of tivozanib or sorafenib, major resection of the stomach or small bowel, or gastric bypass procedure. 19. Psychiatric disorder or altered mental status precluding informed consent or necessary testing. 20. Sexually active pre-menopausal female subjects (and female partners of male subjects) must use adequate contraceptive measures, while on study and for at least 50 days after the last dose of study drug. Sexually active male subjects must use adequate contraceptive measures, while on study and for at least 90 days after the last dose of study drug. All fertile male and female subjects must agree to use a h
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To compare the progression-free survival (PFS) of subjects with advanced renal cell cancer (RCC) randomized to treatment with tivozanib or sorafenib;Secondary Objective: To compare the overall survival (OS) of subjects randomized to treatment with tivozanib or sorafenib To compare objective response rate (ORR) and duration of response (DR) of subjects randomized to treatment with tivozanib or sorafenib To compare the safety and tolerability of tivozanib and sorafenib To compare kidney-specific symptoms and health outcome measurements in subjects randomized to treatment with tivozanib or sorafenib To evaluate the pharmacokinetics (PK) of tivozanib;Primary end point(s): To compare the progression-free survival (PFS) of subjects with advanced renal cell cancer (RCC) randomized to treatment with tivozanib or sorafenib | — |
Countries
Bulgaria, Czech Republic, France, Hungary, Italy, Poland, United Kingdom
Outcome results
None listed