Clinical trial NCT01076010: An Extension Treatment Protocol for Subjects Who Have Participated in a Study of Tivozanib Versus Sorafenib in Kidney Carcinoma (Protocol AV-951-09-301).
Official title: An Extension Treatment Protocol for Subjects Who Have Participated in a Phase 3 Study of Tivozanib vs. Sorafenib in Renal Cell Carcinoma (Protocol AV-951-09-301).
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Advanced Renal Cell Carcinoma
Lead sponsor: AVEO Pharmaceuticals, Inc.
Sponsor class: INDUSTRY
First posted: 2010-02-25
Enrollment: 277
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Open-label, multi-center extension treatment protocol to allow access to tivozanib and sorafenib for subjects who have participated on the AV-951-09-301 protocol. Eligible subjects who were randomized to receive sorafenib on AV-951-09-301 and had documented progression of disease will receive a tivozanib dose of 1.5 mg/day. Eligible subjects who were randomized to tivozanib or sorafenib in AV-951-09-301, and displayed clinical benefit and acceptable tolerability to treatment, will continue to receive tivozanib or sorafenib at the same dose and schedule as in AV-951-09-301.

Detailed description: This is an extension treatment protocol to allow access to tivozanib or sorafenib for subjects enrolled on AV-951-09-301(parent protocol). Subjects who failed sorafenib on the parent protocol will be offered tivozanib. Subjects who were randomized to tivozanib, and demonstrated clinical benefit and acceptable tolerability will be offered long-term access to tivozanib. Subjects who were randomized to sorafenib, and demonstrated clinical benefit and acceptable tolerability will be offered long-term access to sorafenib. Subjects who continue receiving sorafenib on this protocol and progress will be allowed to cross-over to tivozanib.

Eligibility criteria: Inclusion Criteria:

1. The subject must have participated on Protocol AV-951-09-301, and must meet either of the following bulleted criteria:

   * Demonstrated disease progression per RECIST during treatment with sorafenib, OR
   * Demonstrated clinical benefit \[complete response (CR), partial response (PR), or stable disease (SD) per RECIST\] and acceptable tolerability after treatment with tivozanib or sorafenib on protocol AV-951-09-301.
2. Eastern Cooperative Oncology Group performance status ≤ 2 and life expectancy ≥ 3 months.
3. If female and of childbearing potential, documentation of negative pregnancy test prior to enrollment.
4. Ability to give written informed consent

Exclusion Criteria:

1. Newly identified central nervous system (CNS) malignancies or documented progression of CNS metastases; subjects will be allowed only if the CNS metastases have been adequately treated with radiotherapy or surgery. For subjects receiving steroid therapy for allowed steroid maintenance therapy.
2. Duration since last dose on Protocol AV-951-09-301:

   1. For subjects continuing tivozanib or sorafenib (subjects who demonstrated clinical benefit and acceptable tolerability during treatment with tivozanib or sorafenib on protocol AV-951-09-301): more than 2 weeks since last dose of tivozanib or sorafenib.
   2. For subjects initiating tivozanib (ie demonstrated disease progression during treatment with sorafenib): more than 4 weeks since last dose of sorafenib. Subjects demonstrating disease progression due to CNS metastasis will be allowed up to 8 weeks since last dose of sorafenib in order to complete treatment for CNS metastasis.
3. Inadequate recovery from any prior surgical procedure or major surgical procedure within 4 weeks prior to administration of first dose of study drug.
4. Any of the following hematologic abnormalities:

   * Hemoglobin \< 9.0 g/dL
   * Absolute neutrophil count \< 1500 per mm3
   * Platelet count \< 75,000 per mm3
   * Prothrombin time or Partial thromboplastin time \>1.5 × upper limit of normal (ULN)
5. Any of the following serum chemistry abnormalities:

   * Total bilirubin \> 1.5 × ULN (or \> 2.5 × ULN for subjects with Gilbert's syndrome)
   * Aspartate aminotransferase or alanine aminotransferase \> 2.5 × ULN (or \> 5 × ULN for subjects with liver metastasis)
   * Alkaline phosphatase \> 2.5 × ULN (or \> 5 × ULN for subjects with liver or bone metastasis)
   * Creatinine \> 2.0 × ULN
   * Proteinuria \> 3+ by urinalysis or urine dipstick
6. If female, pregnant or lactating.
7. 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,and their partners,must agree to use a highly effective method of contraception. Effective birth control includes (a) Intrauterine device 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).
8. Uncontrolled hypertension: systolic blood pressure \> 150 mmHg or diastolic blood pressure \>100 mmHg on 2 or more antihypertensive medications, documented on 2 consecutive measurements taken at least 24 hours apart.
9. Unhealed wounds (including active peptic ulcers).
10. Serious/active infection or infection requiring parenteral antibiotics.
11. Life-threatening illness or organ system dysfunction compromising safety evaluation.
12. Psychiatric disorder, altered mental status precluding informed consent or necessary testing.
13. Inability to comply with protocol requirements.
14. Treatment with another anti-cancer therapy or participation in another interventional protocol (excluding AV-951-09-301).

Primary outcomes:
measure: Number of Days Subjects Received Treatment in Each Treatment Arm
timeFrame: From enrollment to until all subjects discontinue (due to documented progressive disease [PD] or unacceptable toxicities) or until 3 years after the first subject was enrolled in Protocol AV-951-09-902
measure: Number of Cycles Subjects Received Treatment in Each Treatment Arm
timeFrame: From enrollment to until all subjects discontinue (due to documented PD or unacceptable toxicities) or until 3 years after the first subject was enrolled in Protocol AV-951-09-902
measure: Total Dose Administered to Subjects in Each Treatment Arm (mg)
timeFrame: From enrollment to until all subjects discontinue (due to documented PD or unacceptable toxicities) or until 3 years after the first subject was enrolled in Protocol AV-951-09-902
measure: Average Daily Dose Administered to Subjects in Each Treatment Arm
timeFrame: From enrollment to until all subjects discontinue (due to documented PD or unacceptable toxicities) or until 3 years after the first subject was enrolled in Protocol AV-951-09-902
measure: Relative Dose Intensity (RDI) of Treatment Administered to Subjects in Each Treatment Arm
timeFrame: From enrollment to until all subjects discontinue (due to documented PD or unacceptable toxicities) or until 3 years after the first subject was enrolled in Protocol AV-951-09-902
measure: Number of Subjects With Adverse Events
timeFrame: From enrollment assessed up to 3 years of treatment or until follow-up (up to 30 days end-of-trial visit after treatment discontinuation), whichever occurs earlier
Secondary outcomes:
measure: Number of Subjects With Objective Response Rate (ORR) Who Continued Treatment With Tivozanib or Sorafenib and Who Received Tivozanib After Failure of Sorafenib
timeFrame: From Day 1 to the end of treatment (EOT) Visit, approximately every 8 weeks
measure: Duration of Response (DR)
timeFrame: From the first documentation of objective tumor response to the first documentation of objective tumor progression, assessed up to treatment discontinuation or to death due to any reason or maximum up to 3 years, whichever occurs earlier
measure: Progression-free Survival (PFS)
timeFrame: From the date of first dose of study drug (tivozanib or sorafenib) in the AV-951-09-902 study to the first documentation of objective tumor progression or death due to any reason or maximum up to 3 years, whichever occurred first
measure: Overall Survival (OS)
timeFrame: From the date of first dose of study drug (tivozanib or sorafenib) in the AV-951-09-902 study to death due to any reason or maximum up to 3 years, whichever occurred first
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Site 185
state: California
city: Orlando
country: United States
facility: Site 184
state: Florida
city: Minneapolis
country: United States
facility: Site 182
state: Minnesota
city: New York
country: United States
facility: Site 186
state: New York
city: Dallas
country: United States
facility: Site 187
state: Texas
city: Plovdiv
country: Bulgaria
facility: Site 403
city: Sofia
country: Bulgaria
facility: Site 404
city: Sofia
country: Bulgaria
facility: Site 400
city: Varna
country: Bulgaria
facility: Site 401
city: Veliko Tarnovo
country: Bulgaria
facility: Site 402
city: Montréal
country: Canada
facility: Site 110
state: Quebec
city: Santiago
country: Chile
facility: Site 122
city: Temuco
country: Chile
facility: Site 123
city: Prague 8
country: Czechia
facility: Site 411
city: Saint Herblain Cedex
country: France
facility: Site 133
city: Budapest
country: Hungary
facility: Site 423
city: Kaposvár
country: Hungary
facility: Site 421
city: Pécs
country: Hungary
facility: Site 422
city: Ahmedabad
country: India
facility: Site 156
state: Gujarat
city: Nashik
country: India
facility: Site 151
state: Maharashtra
city: Pune
country: India
facility: Site 153
state: Maharashtra
city: Jaipur
country: India
facility: Site 191
state: Rajasthan
city: Vellore
country: India
facility: Site 152
state: Tamil Nadu
city: Lucknow
country: India
facility: Site 158
state: Uttar Pradesh
city: Kolkata
country: India
facility: Site 150
state: West Bengal
city: Delhi
country: India
facility: Site 154
city: Arezzo
country: Italy
facility: Site 160
city: Pavia
country: Italy
facility: Site 161
city: Roma
country: Italy
facility: Site 162
city: Bialystok
country: Poland
facility: Site 432
city: Bydgoszcz
country: Poland
facility: Site 434
city: Gdansk
country: Poland
facility: Site 431
city: Olsztyn
country: Poland
facility: Site 435
city: Poznan
country: Poland
facility: Site 433
city: Warsaw
country: Poland
facility: Site 430
city: Warsaw
country: Poland
facility: Site 436
city: Brasov
country: Romania
facility: Site 444
city: Bucharest
country: Romania
facility: Site 441
city: Bucharest
country: Romania
facility: Site 440
city: Bucharest
country: Romania
facility: Site 443
city: Timisoara
country: Romania
facility: Site 442
city: Ufa
country: Russian Federation
facility: Site 459
state: Republic Of Bashkortostan
city: Chelyabinsk
country: Russian Federation
facility: Site 451
city: Ekaterinburg
country: Russian Federation
facility: Site 455
city: Kazan
country: Russian Federation
facility: Site 452
city: Moscow
country: Russian Federation
facility: Site 454
city: Moscow
country: Russian Federation
facility: Site 453
city: Moscow
country: Russian Federation
facility: Site 458
city: Moscow
country: Russian Federation
facility: Site 460
city: Moscow
country: Russian Federation
facility: Site 461
city: Moscow
country: Russian Federation
facility: Site 462
city: Nizhny Novgorod
country: Russian Federation
facility: Site 450
city: Obninsk
country: Russian Federation
facility: Site 456
city: Omsk
country: Russian Federation
facility: Site 467
city: Pyatigorsk
country: Russian Federation
facility: Site 463
city: Rostov-on Don
country: Russian Federation
facility: Site 457
city: St. Petersburg
country: Russian Federation
facility: Site 466
city: St. Petersburg
country: Russian Federation
facility: Site 465
city: Yaroslavl
country: Russian Federation
facility: Site 464
city: Belgrade
country: Serbia
facility: Site 480
city: Belgrade
country: Serbia
facility: Site 481
city: Belgrade
country: Serbia
facility: Site 482
city: Nis
country: Serbia
facility: Site 483
city: Sremska Kamenica
country: Serbia
facility: Site 484
city: Chernihiv
country: Ukraine
facility: Site 491
city: Dniproperovsk
country: Ukraine
facility: Site 498
city: Dniproperovsk
country: Ukraine
facility: Site 492
city: Donetsk
country: Ukraine
facility: Site 493
city: Donetsk
country: Ukraine
facility: Site 496
city: Ivano-Frankivsk
country: Ukraine
facility: Site 490
city: Kharkiv
country: Ukraine
facility: Site 494
city: Uzhhorod
country: Ukraine
facility: Site 497
city: Zaporizhia
country: Ukraine
facility: Site 495
city: Cambridge
country: United Kingdom
facility: Site 170
city: Leicester
country: United Kingdom
facility: Site 172
Study officials:
affiliation: Memorial Sloan Kettering Cancer Center
name: Robert J. Motzer, MD
role: PRINCIPAL_INVESTIGATOR
References: