An Extension Treatment Protocol for Subjects who have Participated in a Phase 3 Study of Tivozanib Hydrochloride vs. Sorafenib in Renal Cell Carcinoma (Protocol AV-951-09-301)

• Register: EUCTR
• Last refreshed on: 3 June 2013
• Main ID: EUCTR2009-015987-32-PL
• Date of registration: 06/01/2010
• 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 Hydrochloride 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 Hydrochloride vs. Sorafenib in Renal Cell Carcinoma (Protocol AV-951-09-301) - NA
• Date of first enrolment: 17/02/2010
• Target sample size: 350
• Recruitment status: Authorised-recruitment may be ongoing or finished
• 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: yes Other trial design description: Subjects who demonstrate DP on sorafenib may start tivozanib hydrochloride treatment If controlled, specify comparator, Other Medicinial Product: yes Placebo: no Other: no Number of treatment arms in the trial: 2

Countries of recruitment

Bulgaria, Canada, Chile, Czech Republic, France, Hungary, India, Italy, Poland, Romania, Russian Federation, Serbia, Ukraine, United Kingdom, United States

Contacts

• Name: Margaret M. Taleff/ Vice President
• Affiliation: AVEO Pharmaceuticals, Inc.

• Name: Margaret M. Taleff/ Vice President
• Affiliation: AVEO Pharmaceuticals, Inc.

Key inclusion & exclusion criteria

Inclusion criteria:
Subjects who have discontinued treatment in the AV-951-09-301 protocol and have been undergoing tumor assessment and/or survival follow-up will not need to meet the eligibility criteria (defined below) for their long term follow-up in the current study
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 hydrochloride or sorafenib 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 167
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 79

Exclusion criteria:
1. Newly identified 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 please refer to Section 6.3 for allowed steroid maintenance therapy
2. Duration since last dose on Protocol AV-951-09-301:

For subjects continuing tivozanib hydrochloride or sorafenib (subjects who demonstrated clinical benefit and acceptable tolerability during treatment with tivozanib hydrochloride or sorafenib on protocol AV-951-09-301): more than 2 weeks since last dose of tivozanib hydrochloride or sorafenib

For subjects initiating tivozanib hydrochloride (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
· ANC < 1500 per mm
· 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
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) 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.)
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:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Renal Cell Carcinoma
MedDRA version: 14.1 Level: PT Classification code 10067946 Term: Renal cell carcinoma System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Therapeutic area: Diseases [C] - Cancer [C04]

Intervention(s)

Product Name: Tivozanib Hydrochloride
Product Code: AV-951
Pharmaceutical Form: Capsule
CAS Number: 682745-41-1
Current Sponsor code: AV-951
Other descriptive name: KRN951; Ki19294
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 1.5-

Product Name: Tivozanib Hydrochloride
Product Code: AV-951
Pharmaceutical Form: Capsule
CAS Number: 682745-41-1
Current Sponsor code: AV-951
Other descriptive name: KRN951; Ki19294
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 1.0-

Trade Name: Nexavar
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: SORAFENIB TOSILATE
CAS Number: 475207-59-1
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 200-

Primary Outcome(s)

Primary end point(s): •provide access to tivozanib hydrochloride for subjects who participated in AV-951-09-301 and AV-951-09-902 and failed sorafenib treatment on either protocol
•provide access to tivozanib hydrochloride for subjects who participated in AV-951-09-301 and demonstrated clinical benefit and acceptable tolerability to tivozanib hydrochloride
•provide access to sorafenib subjects who participated in 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 hydrochloride

Main Objective: · To allow access to tivozanib hydrochloride for subjects who participated in Protocol AV-951-09-301 and AV-951-09-902 and failed sorafenib treatment on either protocol.
· To allow long-term access to tivozanib hydrochloride for subjects who participated in Protocol AV-951-09-301 and demonstrated clinical benefit and acceptable tolerability to tivozanib hydrochloride
· 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 hydrochloride

Timepoint(s) of evaluation of this end point: As per study protocol

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 hydrochloride or sorafenib
· To determine the ORR, DR, and PFS of subjects who receive tivozanib hydrochloride after failure of sorafenib
· To determine overall survival (OS) of subjects who continue treatment with tivozanib hydrochloride or sorafenib

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: ORR and DR as well as PFS are measured every two cycles (2 months) by CT scans. OS is assesed every 2 months following treatment discontinuation.

Secondary end point(s): - to determine the ORR, DR and PFS on patients who continue treatment with Tivozanib Hydrochloride or Sorafenib, or who initiate treatment with Tivozanib Hydrochloride after failure on Sorafenib
- and to determine OS of subjects who continue treatment with Tivozanib Hydrochloride or Sorafenib

Secondary ID(s)

2009-015987-32-FR

NCT01076010

AV-951-09-902

Source(s) of Monetary Support

AVEO Pharma Limited

AVEO Pharmaceuticals, Inc.