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)

• Register: EUCTR
• Last refreshed on: 4 April 2022
• Main ID: EUCTR2009-015987-32-FR
• Date of registration: 05/11/2009
• Prospective Registration: Yes
• Primary sponsor: AVEO Pharmaceuticals, Inc.
• Public 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)
• 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: 02/04/2010
• Target sample size: 500
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2009-015987-32
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: yes Single blind: no Double blind: no Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: yes Placebo: Other: Other specify the comparator: Nexavar (sorafenib)
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Bulgaria, Czech Republic, France, Hungary, Italy, Poland, United Kingdom

Key inclusion & exclusion criteria

Inclusion criteria:
1. The subject must have participated on Protocol AV-951-09-301, and must meet at least one of the following criteria:
- Demonstrated disease progression (DP) 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 for up to 2 years on protocol AV-951-09-301
2. ECOG performance status = 2 (see Appendix C) 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
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
1. More than 4 weeks since discontinuation of tivozanib or sorafenib treatment on Protocol AV-951-09-301
2. Any of the following hematologic abnormalities:
• Hemoglobin < 9.0 g/dL
• ANC < 1500 per mm3
• Platelet count < 75,000 per mm3
• PT or PTT >1.5 × ULN
3. Any of the following serum chemistry abnormalities:
• Total bilirubin > 1.5 × ULN (or > 2.5 × ULN for subjects with Gilbert’s syndrome)
• AST or ALT > 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
4 . If female, pregnant or lactating
5. Sexually active male and pre-menopausal female subjects (and their partners) unless they agree to use adequate contraceptive measures, while on study and for 30 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) 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.)
6. 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.
7. Unhealed wounds (including active peptic ulcers)
8. Serious/active infection or infection requiring parenteral antibiotics
9. Life-threatening illness or organ system dysfunction compromising safety evaluation
10. Psychiatric disorder, altered mental status precluding informed consent or necessary testing
11. Inability to comply with protocol requirements


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Advanced Renal Cell Carcinoma
MedDRA version: 12.0 Level: LLT Classification code 10050513 Term: Metastatic renal cell carcinoma

Intervention(s)

Product Name: Tivozanib (AV-951)
Product Code: 1.0 mg
Pharmaceutical Form: Capsule, hard
CAS Number: 682745-41-1
Current Sponsor code: Tivozanib (AV-951)
Other descriptive name: KRN951
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 1.0-

Product Name: Tivozanib (AV-951)
Product Code: 1.5 mg
Pharmaceutical Form: Capsule, hard
CAS Number: 682745-41-1
Current Sponsor code: Tivozanib (AV-951)
Other descriptive name: KRN951
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 1.5-

Trade Name: Nexavar
Product Name: Sorafenib
Pharmaceutical Form: Tablet
INN or Proposed INN: SORAFENIB
CAS Number: 284461-73-0
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 200-

Primary Outcome(s)

Main Objective: • To allow access to tivozanib for subjects who participated in Protocol AV-951-09-301, and failed sorafenib treatment on protocol.
• To allow long-term access to tivozanib for subjects who participated in Protocol AV-951-09-301 and demonstrated clinical benefit and acceptable tolerability to tivozanib
• To allow long-term access to sorafenib for subjects who participated in Protocol AV-951-09-301 and demonstrated clinical benefit and acceptable tolerability to sorafenib
• To assess long-term safety in subjects who continue treatment with tivozanib

Primary end point(s): Study drug may be continued in the absence of disease progression or intolerable toxicities

Discontinuation: Subjects experiencing unacceptable toxicities or with documented disease progression will be discontinued from further participation in this study. However, if a subject is continuing on sorafenib from Protocol AV-951-09-301 and demonstrates disease progression on sorafenib during this protocol, the subject may begin treatment with tivozanib and continue treatment until documented disease progression or unacceptable toxicity related to tivozanib. This study will be discontinued when tivozanib becomes commercially available in the country where the subject is being treated. If a subject is experiencing clinical benefit from tivozanib when the study is discontinued, the sponsor will assist the subject in obtaining commercially available tivozanib.

Secondary Objective: • To determine the objective response rate (ORR), duration of response (DR), and progression-free survival (PFS) of subjects who continue treatment with tivozanib or sorafenib
• To determine the ORR, DR, and PFS of subjects who receive tivozanib after failure of sorafenib
• To determine overall survival (OS) of subjects who continue treatment with tivozanib or sorafenib

Secondary ID(s)

AV-951-09-902

Ethics review

Status: Approved
Approval date: 02/04/2010
Contact:

Results

• Results available: Yes
• Date Posted: 25/08/2021
• Date Completed: 04/07/2014
• URL: https://www.clinicaltrialsregister.eu/ctr-search/trial/2009-015987-32/results