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

  Show 86 Study Locations
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, Renal Cell
Carcinoma
Adenocarcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
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 September 22, 2014