A Clinical Study Comparing the Safety and Effectiveness of Tivozanib (AV-951) Verses Sorafenib for the Treatment of Patients With Advanced Renal Cell Carcinoma

• Conditions: Advanced Renal Cell Carcinoma; MedDRA version: 14.0Level: PTClassification code 10067946Term: Renal cell carcinomaSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)

• Registration Number: EUCTR2009-013219-37-CZ
• Lead Sponsor: AVEO Pharmaceuticals, Inc.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2009-11-18
• Last Update Posted: 10 June 2014

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 500

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

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 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 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 and the

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified