A Study to Compare Tivozanib (AV-951) to Sorafenib in Subjects With Advanced Renal Cell Carcinoma

• Register: ClinicalTrials.gov
• Last refreshed on: 12 December 2020
• Main ID: NCT01030783
• Date of registration: 09/12/2009
• Prospective Registration: No
• Primary sponsor: AVEO Pharmaceuticals, Inc.
• Public title: A Study to Compare Tivozanib (AV-951) to Sorafenib in Subjects With Advanced Renal Cell Carcinoma TIVO-1
• Scientific title: A Phase 3, Randomized, Controlled, Multi-Center, Open-Label Study to Compare Tivozanib (AV-951) to Sorafenib in Subjects With Advanced Renal Cell Carcinoma (TIVO-1)
• Date of first enrolment: December 2009
• Target sample size: 517
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT01030783
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: None (Open Label).
• Phase: Phase 3

Countries of recruitment

Argentina, Bulgaria, Canada, Chile, Czech Republic, Czechia, France, Hungary, India, Italy, Poland, Romania, Russian Federation, Serbia, Ukraine, United Kingdom, United States

Contacts

• Name: Robert J. Motzer, MD
• Affiliation: Memorial Sloan Kettering Cancer Center

Key inclusion & exclusion 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.

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.

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.

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 hematologic abnormalities (as noted in the protocol).

5. Any serum chemistry abnormalities (as noted in the protocol).

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.

12. Significant bleeding disorders within 6 months prior to administration of first dose
of study drug.

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 for at least 90 days after the last dose of drug. All fertile
male and female subjects and their partners must agree to use a highly effective
method of contraception (including their partner). Effective birth control includes
(a) IUD plus one barrier method; or (b) 2 barrier methods. Effective barrier methods
are male or female condoms, diaphragms, and spermicides (creams or gels that contain a
chemical to kill sperm). (Note: Oral, implantable, or injectable contraceptives may be
affected by cytochrome P450 interactions, and are not considered effective for this
study.)



Age minimum: 18 Years
Age maximum: N/A
Gender: All

Health Condition(s) or Problem(s) studied

Advanced Renal Cell Carcinoma

Intervention(s)

Drug: tivozanib (AV-951)

Drug: Sorafenib

Primary Outcome(s)

Progression-free Survival (PFS) of Subjects With Advanced Renal Cell Cancer (RCC) Randomized to Treatment With Tivozanib or Sorafenib [Time Frame: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first. Disease progression was assessed every 8 weeks.]

Secondary Outcome(s)

Overall Survival (OS) of Subjects Randomized to Treatment With Tivozanib or Sorafenib [Time Frame: Date of randomization to date of death]

Safety and Tolerability of Tivozanib and Sorafenib [Time Frame: From start of treatment therapy to completion of treatment therapy, an average of 11 months]

To Compare Kidney-specific Symptoms and Health Outcome Measurements in Subjects Randomized to Treatment With Tivozanib or Sorafenib [Time Frame: At Day 1 of each 28 day cycle throughout the course of the study, for an average of 11 months per subject]

Duration of Response (DR) of Subjects Randomized to Treatment With Tivozanib or Sorafenib [Time Frame: Assessed every 8 weeks from date of randomization until date of progression]

Objective Response Rate (ORR) of Subjects Randomized to Treatment With Tivozanib or Sorafenib [Time Frame: Every 8 weeks from date of randomization until disease progression]

Pharmacokinetics (Serum Concentrations) of Tivozanib [Time Frame: Cycle 1, Day 1 (prior to dosing), Cycle 1, Day 15 (prior to dosing), Cycle 2, Day 1 (prior to dosing), and Cycle 2, Day 22-28]

Secondary ID(s)

AV-951-09-301

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Results

• Results available: Yes
• Date Posted: 28/10/2019
• URL: https://clinicaltrials.gov/ct2/show/results/NCT01030783