A Study to Compare Tivozanib (AV-951) to Sorafenib in Subjects With Advanced Renal Cell Carcinoma (TIVO-1)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
AVEO Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier:
NCT01030783
First received: December 9, 2009
Last updated: February 19, 2014
Last verified: February 2014
  Purpose

This is an open-label, randomized, controlled, multi-national, multi-center, parallel-arm trial comparing tivozanib to sorafenib in subjects with advanced RCC. The study is designed to compare the PFS, OS, ORR, DR, safety and tolerability, and kidney specific symptoms/health outcome measurements of tivozanib and sorafenib.


Condition Intervention Phase
Advanced Renal Cell Carcinoma
Drug: tivozanib (AV-951)
Drug: Sorafenib
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official 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)

Resource links provided by NLM:


Further study details as provided by AVEO Pharmaceuticals, Inc.:

Primary Outcome Measures:
  • To compare the progression-free survival (PFS) of subjects with advanced renal cell cancer (RCC) randomized to treatment with tivozanib or sorafenib [ Time Frame: 24 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • To compare the overall survival (OS) of subjects randomized to treatment with tivozanib or sorafenib [ Time Frame: 24 months ] [ Designated as safety issue: No ]
  • To compare objective response rate (ORR) and duration of response (DR) of subjects randomized to treatment with tivozanib or sorafenib [ Time Frame: 24 months ] [ Designated as safety issue: No ]
  • To compare the safety and tolerability of tivozanib and sorafenib [ Time Frame: 24 months ] [ Designated as safety issue: Yes ]
  • To compare kidney-specific symptoms and health outcome measurements in subjects randomized to treatment with tivozanib or sorafenib [ Time Frame: 24 months ] [ Designated as safety issue: Yes ]
  • To evaluate the pharmacokinetics (PK) of tivozanib [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]

Enrollment: 517
Study Start Date: December 2009
Study Completion Date: June 2013
Primary Completion Date: July 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: tivozanib (AV-951) Drug: tivozanib (AV-951)
Tivozanib: 1.5 mg orally once daily. Subjects will receive 1.5 mg tivozanib once daily beginning on Day 1 for 3 weeks followed by 1 week off treatment. One cycle will be defined as 4 weeks of treatment. Cycles will be repeated every 4 weeks.
Active Comparator: sorafenib Drug: Sorafenib
Sorafenib: 400 mg orally twice daily. Subjects will receive 400 mg (2 x 200 mg tablets) sorafenib twice daily continuously, beginning on Day 1. One cycle will be defined as 4 weeks of treatment. Cycles will be repeated every 4 weeks.

Detailed Description:

This is an open-label, randomized, controlled, multi-national, multi-center, parallel-arm trial comparing tivozanib to sorafenib in subjects with advanced RCC. The study is designed to compare the PFS, OS, ORR, DR, safety and tolerability, and kidney specific symptoms/health outcome measurements of tivozanib and sorafenib.

Subjects will be randomized (1:1) to treatment with tivozanib or sorafenib and stratified by geographic region (North America/Western Europe, Central/Eastern Europe, or rest of the world); number of prior treatments (0 or 1); and number of metastatic sites/organs involved (1 or ≥ 2).

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.)
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01030783

  Hide Study Locations
Locations
United States, California
Site 185
Los Angeles, California, United States, 90095
United States, Florida
Site 180
Gainesville, Florida, United States, 32625
Site 184
Orlando, Florida, United States, 32806
United States, Minnesota
Site 182
Minneapolis, Minnesota, United States, 55455
United States, New York
Site 186
New York, New York, United States, 10065
United States, Texas
Site 187
Dallas, Texas, United States, 75246
Argentina
Site 102
Sante Fe, Argentina, 3077
Bulgaria
Site 403
Plovdiv, Bulgaria, 4004
Site 400
Sofia, Bulgaria, 1756
Site 404
Sofia, Bulgaria, 1431
Site 401
Varna, Bulgaria, 9002
Site 402
Veliko Tarnovo, Bulgaria, 5000
Canada, Quebec
Site 110
Montréal, Quebec, Canada, H2X 1N8
Chile
Site 121
La Reina, Santiago de Chile, Chile, 7510009
Site 122
Santiago, Chile, 8320000
Site 123
Temuco, Chile, 4810469
Czech Republic
Site 411
Prague 8, Czech Republic, 180 81
France
Site 130
Marseille, France, 13009
Site 133
Saint Herblain Cedex, France, 44805
Hungary
Site 423
Budapest, Hungary, H-1108
Site 421
Kaposvár, Hungary, H-7400
Site 422
Pécs, Hungary, H-7624
Site 424
Szombathely, Hungary, H-9700
India
Site 157
Hyderabad, Andhra Pradesh, India, 500004
Site 190
Patna, Bihar, India, 801505
Site 156
Ahmedabad, Gujarat, India, 380015
Site 151
Nashik, Maharashtra, India, 422005
Site 153
Pune, Maharashtra, India, 411004
Site 159
Pune, Maharashtra, India, 411005
Site 155
Jaipur, Rajasthan, India, 302013
Site 191
Jaipur, Rajasthan, India, 302004
Site 152
Vellore, Tamil Nadu, India, 632004
Site 158
Lucknow, Uttar Pradesh, India, 226003
Site 150
Kolkata, West Bengal, India, 700054
Site 154
Delhi, India, 110085
Italy
Site 160
Arezzo, Italy, 52100
Site 161
Pavia, Italy, 27100
Site 162
Roma, Italy, 00152
Poland
Site 432
Bialystok, Poland, 15-027
Site 434
Bydgoszcz, Poland, 85-168
Site 431
Gdansk, Poland, 80-952
Site 435
Olsztyn, Poland, 10-228
Site 433
Poznan, Poland, 61-878
Site 430
Warsaw, Poland, 02-781
Site 436
Warsaw, Poland, 04-141
Romania
Site 444
Brasov, Romania, 500085
Site 443
Bucharest, Romania, 050659
Site 440
Bucharest, Romania, 041345
Site 441
Bucharest, Romania, 022328
Site 442
Timisoara, Romania, 300239
Russian Federation
Site 459
Ufa, Republic of Bashkortostan, Russian Federation, 450054
Site 451
Chelyabinsk, Russian Federation, 454087
Site 455
Ekaterinburg, Russian Federation, 620102
Site 468
Ioshkar Ola, Russian Federation, 424037
Site 452
Kazan, Russian Federation, 420029
Site 454
Moscow, Russian Federation, 105077
Site 462
Moscow, Russian Federation, 125284
Site 458
Moscow, Russian Federation, 115478
Site 461
Moscow, Russian Federation, 115478
Site 460
Moscow, Russian Federation, 115478
Site 453
Moscow, Russian Federation, 115478
Site 450
Nizhny Novgorod, Russian Federation, 603109
Site 456
Obninsk, Russian Federation, 249036
Site 467
Omsk, Russian Federation, 644013
Site 463
Pyatigorsk, Russian Federation, 357500
Site 457
Rostov-on-Don, Russian Federation, 344022
Site 465
St. Petersburg, Russian Federation, 198255
Site 466
St. Petersburg, Russian Federation, 193312
Site 464
Yaroslavi, Russian Federation, 150054
Serbia
Site 480
Belgrade, Serbia, 11000
Site 481
Belgrade, Serbia, 11000
Site 482
Belgrade, Serbia, 11000
Site 483
Nis, Serbia, 18000
Site 484
Sremska Kamenica, Serbia, 21204
Ukraine
Site 491
Chernihiv, Ukraine, 14029
Site 492
Dniproperovsk, Ukraine, 49102
Site 498
Dnipropetrovsk, Ukraine, 49005
Site 493
Donetsk, Ukraine, 83092
Site 496
Donetsk, Ukraine, 83092
Site 490
Ivano-Frankivsk, Ukraine, 76000
Site 494
Kharkiv, Ukraine, 61037
Site 497
Uzhhorod, Ukraine, 88014
Site 495
Zaporizhia, Ukraine, 69600
United Kingdom
Site 170
Cambridge, United Kingdom, CB2 0QQ
Site 173
Ipswich, United Kingdom, IP4 5WW
Site 172
Leicester, United Kingdom, LE1 5WW
Sponsors and Collaborators
AVEO Pharmaceuticals, Inc.
Investigators
Principal Investigator: Robert J. Motzer, MD Memorial Sloan-Kettering Cancer Center
  More Information

Additional Information:
No publications provided

Responsible Party: AVEO Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier: NCT01030783     History of Changes
Other Study ID Numbers: AV-951-09-301
Study First Received: December 9, 2009
Last Updated: February 19, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Carcinoma
Carcinoma, Renal Cell
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Adenocarcinoma
Kidney Neoplasms
Urologic Neoplasms
Urogenital Neoplasms
Neoplasms by Site
Kidney Diseases
Urologic Diseases
Sorafenib
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on August 01, 2014