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CompletedNCT01076010Updated Oct 5, 2020Results posted

An Extension Treatment Protocol for Subjects Who Have Participated in a Study of Tivozanib Versus Sorafenib in Kidney Carcinoma (Protocol AV-951-09-301).

A Phase 3 interventional study of Tivozanib and Sorafenib in Advanced Renal Cell Carcinoma, sponsored by AVEO Pharmaceuticals, Inc.. Completed at 75 sites in 15 countries. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2020-10-05.

Sponsored by AVEO Pharmaceuticals, Inc. · Phase 3, Interventional, and Treatment

Phase
Phase 3
Study type
Interventional
Enrollment
277
Allocation
Non-randomized
Ages
18 Years and older
Sex
All
01

Study 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.

Read the 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.

02

Conditions studied

  • Advanced Renal Cell Carcinoma
03

In context

Carcinoma

6,741 studies on the registry are indexed under Carcinoma; 1,161 are open to participants now.

This study's enrollment of 277 is above the median of 45 across 5,170 interventional studies indexed under Carcinoma.

Browse Carcinoma studies →

Lead sponsor

AVEO Pharmaceuticals, Inc. is the lead sponsor of 34 studies on the registry; 2 are open to participants now.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years and older
Sexes eligible
All
Accepts healthy volunteers
No

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

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).
05

Study design

Phase
Phase 3
Primary purpose
Treatment
Allocation
Non-randomized
Intervention model
Parallel assignment
Masking
None (open label)
Enrollment
277 participants (actual)

Study arms

  • Experimental
    Sorafenib crossover to tivozanib.

    The subjects who failed sorafenib (had Response Evaluation Criteria in Solid Tumors \[RECIST\] - defined progressive disease) on the parent protocol AV-951-09-301 will be offered tivozanib hydrochloride on Protocol AV- 951-09-902.

    Drug: Tivozanib · Drug: Sorafenib

  • Experimental
    First line tivozanib.

    The subjects who were randomized to tivozanib (continued from the parent Protocol AV-951-09-301) and demonstrated clinical benefit and acceptable tolerability in Protocol AV-951-09-301.

    Drug: Tivozanib

  • Active comparator
    First line sorafenib.

    The subjects who were randomized to sorafenib (continued from the parent Protocol AV-951-09-301) and demonstrated clinical benefit and acceptable tolerability were to be offered long-term access to sorafenib.

    Drug: Sorafenib

Interventions

  • DrugTivozanib

    Tivozanib capsules, administered orally, on a dosing schedule of 3 weeks of treatment (beginning on Day 1) followed by 1 week off treatment. One cycle was defined as 4 weeks of treatment.

  • DrugSorafenib

    Sorafenib tablets, 400 mg twice daily, administered orally for 4 weeks (1 cycle = 4 weeks). One cycle was defined as 4 weeks of treatment. Cycles were repeated every 4 weeks.

06

What researchers measure

Primary outcomes

  1. Number of Days Subjects Received Treatment in Each Treatment Arm

    Number of days subjects received treatment who were from Protocol AV-951-09-301 who either continued on tivozanib in this trial (subjects with first-line experience on tivozanib treatment), who crossed over from sorafenib to tivozanib in this trial (crossover subjects) participated in, and who continued on sorafenib in this trial (subjects with first-line experience on sorafenib treatment). Subjects could be discontinued due to unacceptable toxicities or clinical or documented PD

    Time frame: 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

  2. Number of Cycles Subjects Received Treatment in Each Treatment Arm

    Number of cycles subjects received who were from Protocol AV-951-09-301 who either continued on tivozanib in this trial (subjects with first-line experience on tivozanib treatment), who crossed over from sorafenib to tivozanib in this trial (crossover subjects) participated in, and who continued on sorafenib in this trial (subjects with first-line experience on sorafenib treatment). Subjects could be discontinued due to unacceptable toxicities or clinical or documented PD

    Time frame: 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

  3. Total Dose Administered to Subjects in Each Treatment Arm (mg)

    The total dose administered to subjects who were from Protocol AV-951-09-301 who either continued on tivozanib in this trial (subjects with first-line experience on tivozanib treatment), who crossed over from sorafenib to tivozanib in this trial (crossover subjects) participated in, and who continued on sorafenib in this trial (subjects with first-line experience on sorafenib treatment). Subjects could be discontinued due to unacceptable toxicities or clinical or documented PD

    Time frame: 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

  4. Average Daily Dose Administered to Subjects in Each Treatment Arm

    The average daily dose administered to subjects who were from Protocol AV-951-09-301 who either continued on tivozanib in this trial (subjects with first-line experience on tivozanib treatment), who crossed over from sorafenib to tivozanib in this trial (crossover subjects) participated in, and who continued on sorafenib in this trial (subjects with first-line experience on sorafenib treatment). Subjects could be discontinued due to unacceptable toxicities or clinical or documented PD

    Time frame: 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

  5. Relative Dose Intensity (RDI) of Treatment Administered to Subjects in Each Treatment Arm

    RDI is defined as 100% times the actual dose intensity divided by the intended dose intensity. The RDI of subjects who were from Protocol AV-951-09-301 who either continued on tivozanib in this trial (subjects with first-line experience on tivozanib treatment), who crossed over from sorafenib to tivozanib in this trial (crossover subjects) participated in, and who continued on sorafenib in this trial (subjects with first-line experience on sorafenib treatment). Subjects could be discontinued due to unacceptable toxicities or clinical or documented PD

    Time frame: 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

  6. Number of Subjects With Adverse Events

    Number of subjects with Treatment-Related Adverse Events (AEs) as assessed by Common Terminology Criteria for Adverse Events v3.0

    Time frame: 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

  1. Number of Subjects With Objective Response Rate (ORR) Who Continued Treatment With Tivozanib or Sorafenib and Who Received Tivozanib After Failure of Sorafenib

    ORR is defined as the proportion of subjects with confirmed complete response (CR) or confirmed partial response (PR) according to RECIST (Version 1.0), relative to the total population of dosed subjects. CR is disappearance of all target and non-target lesions and normalization of tumor marker levels. At least a 30% decrease in the sum of the loading dose (LD) of target lesions, taking as reference the baseline sum LD. To allow long-term access to sorafenib for subjects who participated in Protocol AV-951-09-301 (NCT01030783), and demonstrated clinical benefit and acceptable tolerability to sorafenib.

    Time frame: From Day 1 to the end of treatment (EOT) Visit, approximately every 8 weeks

  2. Duration of Response (DR)

    DR was defined as the time from the first documentation of objective tumor response (confirmed CR or confirmed PR) according to RECIST (Version 1.0) to the first documentation of objective tumor progression or to death due to any reason. DR was calculated for the subgroup of subjects with a confirmed objective tumor response (PR or CR). CR is Disappearance of all target and non-target lesions and normalization of tumor marker levels. PR is At least a 30% decrease in the sum of the LD of target lesions, taking as reference the baseline sum LD. Number of subjects with disease progression or death and censored endpoints were summarized and statistical analysis were performed for duration of response.

    Time frame: 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

  3. Progression-free Survival (PFS)

    PFS was defined as the date of first dose of study drug to the first documentation of objective tumor progression or death due to any reason, whichever occurred first. For the crossover subjects and subjects with first-line experience on tivozanib treatment, the timeframe for PFS assessment started from the date of first dose of tivozanib in the AV-951-09-902 study. For subjects with first-line experience on sorafenib treatment, the timeframe for PFS assessment started from the date of first dose of sorafenib in the AV-951-09-902. Number of subjects with disease progression or death was summarized and statistical analysis were performed for PFS.

    Time frame: 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

  4. Overall Survival (OS)

    OS was defined as the time from the first dose of study drug (tivozanib or sorafenib) date on this study to date of death due to any cause. Number of subjects died or alive was summarized and statistical analysis were performed for OS.

    Time frame: 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

07

Results

Posted Oct 5, 2020

Participant flow

Subjects were enrolled at 55 sites in 14 countries. Study Period from 24 May 2010 (First Subject Dosed) to 04 July 2014 (Last Subject Last Visit).

Participant flow — Overall Study
MilestoneSorafenib Crossover to TivozanibFirst Line Tivozanib.First Line Sorafenib.
Started1618828
Completed364926
Not completed125392
Withdrew: Death1510
Withdrew: Adverse event720
Withdrew: Progressive disease90301
Withdrew: Lack of efficacy400
Withdrew: Treatment interruption for > 2 weeks010
Withdrew: Significant surgical procedure010
Withdrew: Protocol violation010
Withdrew: Noncompliance110
Withdrew: Withdrawal by subject301
Withdrew: Other520

Outcome measures

PrimaryNumber of Days Subjects Received Treatment in Each Treatment Arm

Number of days subjects received treatment who were from Protocol AV-951-09-301 who either continued on tivozanib in this trial (subjects with first-line experience on tivozanib treatment), who crossed over from sorafenib to tivozanib in this trial (crossover subjects) participated in, and who continued on sorafenib in this trial (subjects with first-line experience on sorafenib treatment). Subjects could be discontinued due to unacceptable toxicities or clinical or documented PD

Time frame:
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
Reported as:
Mean · Days
Number of Days Subjects Received Treatment in Each Treatment Arm
DaysSorafenib Crossover to TivozanibFirst Line Tivozanib.First Line Sorafenib.
Duration of Treatment290 ± 234.37325.3 ± 137.79369.4 ± 107.6
Total Days Receiving Drug222.36 ± 181.722241.0 ± 105.928368.14 ± 107.946
PrimaryNumber of Cycles Subjects Received Treatment in Each Treatment Arm

Number of cycles subjects received who were from Protocol AV-951-09-301 who either continued on tivozanib in this trial (subjects with first-line experience on tivozanib treatment), who crossed over from sorafenib to tivozanib in this trial (crossover subjects) participated in, and who continued on sorafenib in this trial (subjects with first-line experience on sorafenib treatment). Subjects could be discontinued due to unacceptable toxicities or clinical or documented PD

Time frame:
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
Reported as:
Mean · Number of cycles started
Number of Cycles Subjects Received Treatment in Each Treatment Arm
Number of cycles startedSorafenib Crossover to TivozanibFirst Line Tivozanib.First Line Sorafenib.
Number of Cycles Subjects Received Treatment in Each Treatment Arm10.6 ± 8.3611.8 ± 4.8513.2 ± 3.83
PrimaryTotal Dose Administered to Subjects in Each Treatment Arm (mg)

The total dose administered to subjects who were from Protocol AV-951-09-301 who either continued on tivozanib in this trial (subjects with first-line experience on tivozanib treatment), who crossed over from sorafenib to tivozanib in this trial (crossover subjects) participated in, and who continued on sorafenib in this trial (subjects with first-line experience on sorafenib treatment). Subjects could be discontinued due to unacceptable toxicities or clinical or documented PD

Time frame:
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
Reported as:
Mean · mg
Total Dose Administered to Subjects in Each Treatment Arm (mg)
mgSorafenib Crossover to TivozanibFirst Line Tivozanib.First Line Sorafenib.
Total Dose Administered to Subjects in Each Treatment Arm (mg)318.84 ± 256.241344.58 ± 152.131244014.29 ± 116816.715
PrimaryAverage Daily Dose Administered to Subjects in Each Treatment Arm

The average daily dose administered to subjects who were from Protocol AV-951-09-301 who either continued on tivozanib in this trial (subjects with first-line experience on tivozanib treatment), who crossed over from sorafenib to tivozanib in this trial (crossover subjects) participated in, and who continued on sorafenib in this trial (subjects with first-line experience on sorafenib treatment). Subjects could be discontinued due to unacceptable toxicities or clinical or documented PD

Time frame:
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
Reported as:
Mean · mg/day
Average Daily Dose Administered to Subjects in Each Treatment Arm
mg/daySorafenib Crossover to TivozanibFirst Line Tivozanib.First Line Sorafenib.
Average Daily Dose Administered to Subjects in Each Treatment Arm1.46 ± 0.1211.40 ± 0.196651.47 ± 225.410
PrimaryRelative Dose Intensity (RDI) of Treatment Administered to Subjects in Each Treatment Arm

RDI is defined as 100% times the actual dose intensity divided by the intended dose intensity. The RDI of subjects who were from Protocol AV-951-09-301 who either continued on tivozanib in this trial (subjects with first-line experience on tivozanib treatment), who crossed over from sorafenib to tivozanib in this trial (crossover subjects) participated in, and who continued on sorafenib in this trial (subjects with first-line experience on sorafenib treatment). Subjects could be discontinued due to unacceptable toxicities or clinical or documented PD

Time frame:
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
Reported as:
Mean · percentage of dose
Relative Dose Intensity (RDI) of Treatment Administered to Subjects in Each Treatment Arm
percentage of doseSorafenib Crossover to TivozanibFirst Line Tivozanib.First Line Sorafenib.
Relative Dose Intensity (RDI) of Treatment Administered to Subjects in Each Treatment Arm95.21 ± 9.39391.12 ± 14.76280.60 ± 28.603
PrimaryNumber of Subjects With Adverse Events

Number of subjects with Treatment-Related Adverse Events (AEs) as assessed by Common Terminology Criteria for Adverse Events v3.0

Time frame:
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
Reported as:
Count of participants · Participants
Number of Subjects With Adverse Events
ParticipantsSorafenib Crossover to TivozanibFirst Line Tivozanib.First Line Sorafenib.
AE1248528
Any AE of Grade 3 or Higher775519
Any Treatment-Related AE867627
Any Treatment-Related Any Treatment AE ≥ Grade 3393515
Any AE With Outcome of Death2130
Any treatment-Related AE With Outcome of death110
Any serious adverse event (SAE)49174
Any treatment-related SAE772
AE leading to study drug discontinuation (AEDC)1940
Any treatment-related AEDC300
AE leading to study drug interruption272612
Treatment-related AE - study drug interruption131710
AE Leading to Study Drug Dose Reduction111110
Treatment related AE - Study Drug Dose Reduction91110
SecondaryNumber of Subjects With Objective Response Rate (ORR) Who Continued Treatment With Tivozanib or Sorafenib and Who Received Tivozanib After Failure of Sorafenib

ORR is defined as the proportion of subjects with confirmed complete response (CR) or confirmed partial response (PR) according to RECIST (Version 1.0), relative to the total population of dosed subjects. CR is disappearance of all target and non-target lesions and normalization of tumor marker levels. At least a 30% decrease in the sum of the loading dose (LD) of target lesions, taking as reference the baseline sum LD. To allow long-term access to sorafenib for subjects who participated in Protocol AV-951-09-301 (NCT01030783), and demonstrated clinical benefit and acceptable tolerability to sorafenib.

Time frame:
From Day 1 to the end of treatment (EOT) Visit, approximately every 8 weeks
Reported as:
Count of participants · Participants
Number of Subjects With Objective Response Rate (ORR) Who Continued Treatment With Tivozanib or Sorafenib and Who Received Tivozanib After Failure of Sorafenib
ParticipantsSorafenib Crossover to TivozanibFirst Line Tivozanib.First Line Sorafenib.
Overall Confirmed Objective Response Rate294916
Overall Unconfirmed Objective Response Rate435516
SecondaryDuration of Response (DR)

DR was defined as the time from the first documentation of objective tumor response (confirmed CR or confirmed PR) according to RECIST (Version 1.0) to the first documentation of objective tumor progression or to death due to any reason. DR was calculated for the subgroup of subjects with a confirmed objective tumor response (PR or CR). CR is Disappearance of all target and non-target lesions and normalization of tumor marker levels. PR is At least a 30% decrease in the sum of the LD of target lesions, taking as reference the baseline sum LD. Number of subjects with disease progression or death and censored endpoints were summarized and statistical analysis were performed for duration of response.

Time frame:
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
Reported as:
Count of participants · Participants
Duration of Response (DR)
ParticipantsSorafenib Crossover to TivozanibFirst Line Tivozanib.First Line Sorafenib.
Subjects who had disease progression or died10110
Subjects with censored endpoints193816
Statistical analysis
  • Sorafenib Crossover to Tivozanib · 25% quartile (months): 8.0 · 95% CI 4.4 to 12.9
  • Sorafenib Crossover to Tivozanib · 50% quartile (months): 15.2
  • First Line Tivozanib. · 25% quartile (months): 12.9
SecondaryProgression-free Survival (PFS)

PFS was defined as the date of first dose of study drug to the first documentation of objective tumor progression or death due to any reason, whichever occurred first. For the crossover subjects and subjects with first-line experience on tivozanib treatment, the timeframe for PFS assessment started from the date of first dose of tivozanib in the AV-951-09-902 study. For subjects with first-line experience on sorafenib treatment, the timeframe for PFS assessment started from the date of first dose of sorafenib in the AV-951-09-902. Number of subjects with disease progression or death was summarized and statistical analysis were performed for PFS.

Time frame:
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
Reported as:
Count of participants · Participants
Progression-free Survival (PFS)
ParticipantsSorafenib Crossover to TivozanibFirst Line Tivozanib.First Line Sorafenib.
Subjects who had disease progression or died108351
Subjects with censored endpoints535327
Statistical analysis
  • Sorafenib Crossover to Tivozanib · 25% quartile (months): 3.6 · 95% CI 1.9 to 5.2
  • Sorafenib Crossover to Tivozanib · 50% quartile (months): 11.0 · 95% CI 7.3 to 12.7
  • Sorafenib Crossover to Tivozanib · 75% quartile (months): 20.9
  • First Line Tivozanib. · 25% quartile (months): 7.2 · 95% CI 3.5 to 9.2
SecondaryOverall Survival (OS)

OS was defined as the time from the first dose of study drug (tivozanib or sorafenib) date on this study to date of death due to any cause. Number of subjects died or alive was summarized and statistical analysis were performed for OS.

Time frame:
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
Reported as:
Count of participants · Participants
Overall Survival (OS)
ParticipantsSorafenib Crossover to TivozanibFirst Line Tivozanib.First Line Sorafenib.
Died78100
Alive837828
Statistical analysis
  • Sorafenib Crossover to Tivozanib · 25% quartile (months): 8.2 · 95% CI 6.0 to 12.1
  • Sorafenib Crossover to Tivozanib · 50% quartile (months): 21.6 · 95% CI 17.0 to 27.6
  • Sorafenib Crossover to Tivozanib · 75% quartile (months): 30.7

Adverse events

Collected over 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. Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Sorafenib Crossover to Tivozanib—49/161 (30.4%)87/161 (54%)
First Line Tivozanib—17/88 (19.3%)82/88 (93.2%)
First Line Sorafenib—4/28 (14.3%)28/28 (100%)
Most frequent serious events
Showing 10 of 64
Most frequent serious events
EventSorafenib Crossover to TivozanibFirst Line TivozanibFirst Line Sorafenib
PleurisyRespiratory, thoracic and mediastinal disorders1/1610/881/28
Renal failure acuteRenal and urinary disorders0/1611/881/28
Salivary gland massGastrointestinal disorders0/1610/881/28
Device related infectionInfections and infestations0/1610/881/28
DiverticulitisInfections and infestations0/1610/881/28
Peripheral ischaemiaVascular disorders0/1610/881/28
Neoplasm progressionNeoplasms benign, malignant and unspecified (incl cysts and polyps)4/1610/880/28
Renal cancerNeoplasms benign, malignant and unspecified (incl cysts and polyps)3/1610/880/28
AnaemiaBlood and lymphatic system disorders3/1610/880/28
Acute myocardial infarctionCardiac disorders2/1610/880/28
Most frequent other events
Showing 10 of 49
Most frequent other events
EventSorafenib Crossover to TivozanibFirst Line TivozanibFirst Line Sorafenib
HypertensionVascular disorders41/16144/8816/28
Palmar-plantar erythrodysaesthesia syndromeSkin and subcutaneous tissue disorders16/16121/8816/28
DiarrhoeaGastrointestinal disorders22/16135/8812/28
Weight decreasedInvestigations0/16121/889/28
NauseaGastrointestinal disorders0/16121/880/28
FatigueGeneral disorders21/16120/883/28
AstheniaGeneral disorders20/16120/883/28
alopeciaSkin and subcutaneous tissue disorders0/1610/886/28
DysphoniaRespiratory, thoracic and mediastinal disorders9/16116/880/28
Blood phosphorus decreasedInvestigations0/1610/885/28

Baseline characteristics

Age, Categorical
Age, Categorical(Participants)Sorafenib Crossover to TivozanibFirst Line TivozanibFirst Line SorafenibTotal
<=18 years0000
Between 18 and 65 years1205817195
>=65 years41301182
Sex: Female, Male
Sex: Female, Male(Participants)Sorafenib Crossover to TivozanibFirst Line TivozanibFirst Line SorafenibTotal
Female4633988
Male1155519189
Ethnicity (NIH/OMB)
Ethnicity (NIH/OMB)(Participants)Sorafenib Crossover to TivozanibFirst Line TivozanibFirst Line SorafenibTotal
Hispanic or Latino7209
Not Hispanic or Latino1548428266
Unknown or Not Reported0202
Race (NIH/OMB)
Race (NIH/OMB)(Participants)Sorafenib Crossover to TivozanibFirst Line TivozanibFirst Line SorafenibTotal
American Indian or Alaska Native0000
Asian5106
Native Hawaiian or Other Pacific Islander0000
Black or African American0000
White1568728271
More than one race0000
Unknown or Not Reported0000
08

Study locations

75 sites
  • Site 185
    Los Angeles, California 90095, United States
  • Site 184
    Orlando, Florida 32806, United States
  • Site 182
    Minneapolis, Minnesota 55455, United States
  • Site 186
    New York, New York 10065-6007, United States
  • Site 187
    Dallas, Texas 75246, United States
  • Site 403
    Plovdiv, 4004, Bulgaria
  • Site 404
    Sofia, 1431, Bulgaria
  • Site 400
    Sofia, 1756, Bulgaria
  • Site 401
    Varna, 9002, Bulgaria
  • Site 402
    Veliko Tarnovo, 5000, Bulgaria
  • Site 110
    Montréal, Quebec H2X 1N8, Canada
  • Site 122
    Santiago, 8320000, Chile
  • Site 123
    Temuco, 4810469, Chile
  • Site 411
    Prague 8, 180 81, Czechia
  • Site 133
    Saint Herblain Cedex, 44805, France
  • Site 423
    Budapest, H-1108, Hungary
  • Site 421
    Kaposvár, H-7400, Hungary
  • Site 422
    Pécs, H-7624, Hungary
  • Site 156
    Ahmedabad, Gujarat 380015, India
  • Site 151
    Nashik, Maharashtra 422005, India
  • Site 153
    Pune, Maharashtra 411004, India
  • Site 191
    Jaipur, Rajasthan 302004, India
  • Site 152
    Vellore, Tamil Nadu 632004, India
  • Site 158
    Lucknow, Uttar Pradesh 226003, India
  • Site 150
    Kolkata, West Bengal 700054, India
  • Site 154
    Delhi, 110085, India
  • Site 160
    Arezzo, 52100, Italy
  • Site 161
    Pavia, 27100, Italy
  • Site 162
    Roma, 00152, Italy
  • Site 432
    Bialystok, 15-027, Poland
  • Site 434
    Bydgoszcz, 85-168, Poland
  • Site 431
    Gdansk, 80-952, Poland
  • Site 435
    Olsztyn, 10-228, Poland
  • Site 433
    Poznan, 61-878, Poland
  • Site 430
    Warsaw, 02-781, Poland
  • Site 436
    Warsaw, 04-141, Poland
  • Site 444
    Brasov, 500085, Romania
  • Site 441
    Bucharest, 022328, Romania
  • Site 440
    Bucharest, 041345, Romania
  • Site 443
    Bucharest, 050659, Romania
  • Site 442
    Timisoara, 300239, Romania
  • Site 459
    Ufa, Republic Of Bashkortostan 450054, Russian Federation
  • Site 451
    Chelyabinsk, 454087, Russian Federation
  • Site 455
    Ekaterinburg, 620102, Russian Federation
  • Site 452
    Kazan, 420029, Russian Federation
  • Site 454
    Moscow, 105077, Russian Federation
  • Site 453
    Moscow, 115478, Russian Federation
  • Site 458
    Moscow, 115478, Russian Federation
  • Site 460
    Moscow, 115478, Russian Federation
  • Site 461
    Moscow, 115478, Russian Federation
  • Site 462
    Moscow, 125284, Russian Federation
  • Site 450
    Nizhny Novgorod, 603109, Russian Federation
  • Site 456
    Obninsk, 249036, Russian Federation
  • Site 467
    Omsk, 644013, Russian Federation
  • Site 463
    Pyatigorsk, 357500, Russian Federation
  • Site 457
    Rostov-on Don, 344022, Russian Federation
  • Site 466
    St. Petersburg, 193312, Russian Federation
  • Site 465
    St. Petersburg, 198255, Russian Federation
  • Site 464
    Yaroslavl, 150054, Russian Federation
  • Site 480
    Belgrade, 11000, Serbia
  • Site 481
    Belgrade, 11000, Serbia
  • Site 482
    Belgrade, 11000, Serbia
  • Site 483
    Nis, 18000, Serbia
  • Site 484
    Sremska Kamenica, 21204, Serbia
  • Site 491
    Chernihiv, 14029, Ukraine
  • Site 498
    Dniproperovsk, 49005, Ukraine
  • Site 492
    Dniproperovsk, 49102, Ukraine
  • Site 493
    Donetsk, 83092, Ukraine
  • Site 496
    Donetsk, 83092, Ukraine
  • Site 490
    Ivano-Frankivsk, 76000, Ukraine
  • Site 494
    Kharkiv, 61037, Ukraine
  • Site 497
    Uzhhorod, 88014, Ukraine
  • Site 495
    Zaporizhia, 69600, Ukraine
  • Site 170
    Cambridge, CB2 0QQ, United Kingdom
  • Site 172
    Leicester, LE1 5WW, United Kingdom
09

References and documents

Related links

10

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Oct 5, 2020, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
11

Registry details

Key details

Study ID
NCT01076010
Lead sponsor
AVEO Pharmaceuticals, Inc.
Responsible party
Sponsor
First posted
Feb 25, 2010
Start date
Mar 2010
Primary completion
Jul 2014
Completion
Jul 2014
Results posted
Oct 5, 2020
Last update
Oct 5, 2020

Study contacts

Robert J. Motzer, MD
principal investigator · Memorial Sloan Kettering Cancer Center

Oversight

Data monitoring committee
No
View the source record on ClinicalTrials.gov ↗

Not currently enrolling

This study is completed, as verified in Sep 2020. You cannot join it, but the record below documents what was studied.

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