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

• Register: ClinicalTrials.gov
• Last refreshed on: 12 December 2020
• Main ID: NCT01076010
• Date of registration: 24/02/2010
• Prospective Registration: Yes
• Primary sponsor: AVEO Pharmaceuticals, Inc.
• Public title: An Extension Treatment Protocol for Subjects Who Have Participated in a Study of Tivozanib Versus Sorafenib in Kidney Carcinoma (Protocol AV-951-09-301).
• Scientific 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).
• Date of first enrolment: March 2010
• Target sample size: 277
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT01076010
• Study type: Interventional
• Study design: Allocation: Non-Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: None (Open Label).
• Phase: Phase 3

Countries of recruitment

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. 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).



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

Health Condition(s) or Problem(s) studied

Advanced Renal Cell Carcinoma

Intervention(s)

Drug: Sorafenib

Drug: Tivozanib

Primary Outcome(s)

Number of Cycles Subjects Received Treatment in Each Treatment Arm [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]

Number of Days Subjects Received Treatment in Each Treatment Arm [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]

Total Dose Administered to Subjects in Each Treatment Arm (mg) [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]

Relative Dose Intensity (RDI) of Treatment Administered to Subjects in Each Treatment Arm [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]

Average Daily Dose Administered to Subjects in Each Treatment Arm [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]

Number of Subjects With Adverse Events [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 Outcome(s)

Progression-free Survival (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]

Number of Subjects With Objective Response Rate (ORR) Who Continued Treatment With Tivozanib or Sorafenib and Who Received Tivozanib After Failure of Sorafenib [Time Frame: From Day 1 to the end of treatment (EOT) Visit, approximately every 8 weeks]

Overall Survival (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]

Duration of Response (DR) [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]

Secondary ID(s)

2009-015987-32

AV-951-09-902

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Results

• Results available: Yes
• Date Posted: 05/10/2020
• URL: https://clinicaltrials.gov/ct2/show/results/NCT01076010