Objectives:• To allow continued access to tivozanib for subjects who have participated in other tivozanib (monotherapy orcombination) protocols, who are tolerating study drug and displaying clinical benefit.• To assess long-term safety and…
ID
Source
Brief title
Condition
- Miscellaneous and site unspecified neoplasms benign
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Patients will be observed for adverse events and tumor growth.
Secondary outcome
To determine the duration of response and progression-free survival (PFS) of
subjects
who continue on tivozanib.
Background summary
The formation of new blood vessels, known as angiogenesis, is required to
support growth in the
embryo and to allow for repair (e.g., wound healing and remodeling processes in
the adult).
Vascular endothelial growth factor (VEGF) plays a critical role during normal
embryonic
angiogenesis and also in the pathological angiogenesis that occurs in a number
of diseases,
including cancer. Tumors use this vasculature to obtain oxygen and nutrients,
both of
which are required to sustain tumor growth. In addition, the new intra-tumoral
blood vessels
provide a way for tumor cells to enter the circulation and to metastasize to
distant organs.
The various forms of VEGF bind to 3 tyrosine kinase receptors: the vascular
endothelial growth
factor receptors, VEGFR-1, VEGFR-2, and VEGFR-3. This binding results in
phosphorylation
of the receptors catalyzed by the protein kinase, and the promotion of a signal
transduction
cascade. Deregulation of VEGF expression contributes to the development of
solid tumors by
promoting tumor angiogenesis. Tivozanib inhibits VEGFR-associated tyrosine
kinase
activity and, as a result, may offer a potential therapy for subjects with
cancer by controlling
tumor growth.
Study objective
Objectives:
• To allow continued access to tivozanib for subjects who have participated in
other tivozanib (monotherapy or
combination) protocols, who are tolerating study drug and displaying clinical
benefit.
• To assess long-term safety and tolerability in subjects who continue on
tivozanib
• To determine the duration of response and progression-free survival (PFS) of
subjects who continue on
tivozanib
Study design
Open-label, multi-center, multi-national rollover study to allow continued
access to tivozanib for
subjects who have participated in other tivozanib (monotherapy or combination)
protocols. Eligible subjects will
continue to receive tivozanib at the same dose and schedule as per the original
(parent) protocol. The length of time
that a subject must be on the parent protocol before rolling over to this
protocol will be dictated by the (original)
parent protocol.
Intervention
Patients will receive tivozanib according to the previous guidelines of the
study in which they participated.
Study burden and risks
Hypertension has been the primary AE observed in the Phase 1 and 2 monotherapy
studies of
tivozanib in subjects with solid tumors. Hypertension is a frequent and
controllable side-effect
of drugs targeting the vascular endothelial growth factor (VEGF) pathway, and
has been
observed with varying frequency with several approved agents in clinical use
such as
bevacizumab, sunitinib, and sorafenib.
The patients entered in this study had at least stable disease in a previous
study and will therefore benefit of continued treatment with tivozanib.
650 Kendall Street 650
Cambridge MA 02142
US
650 Kendall Street 650
Cambridge MA 02142
US
Listed location countries
Age
Inclusion criteria
1. The subject must have received tivozanib hydrochloride while enrolled in another protocol, must be tolerating study drug and must currently display clinical benefit. The length of time that a subject must be on the parent protocol before rolling over to this protocol will be dictated by the parent protocol.
a. Subjects who received tivozanib hydrochloride at any time while on parent protocol AV-951-12-205, regardless of sequence, may enroll if they tolerated and displayed clinical benefit while receiving tivozanib hydrochloride.
b. Subjects receiving sorafenib in Study AV-951-09-902 who were tolerating sorafenib and displaying clinical benefit at the time of study termination may initiate tivozanib hydrochloride as a treatment option.
2. If female and of childbearing potential, documentation of negative pregnancy test prior to enrollment (i.e. before the first dose of tivozanib hydrochloride in this protocol).
3. Ability to give written informed consent.
Exclusion criteria
1. Subjects to be excluded > 4 weeks since discontinuation of study drug treatment on a previous AVEO-sponsored clinical trial.
a. For subjects initiating tivozanib hydrochloride (ie receiving sorafenib and demonstrating tolerability and clinical benefit on Study AV-951-09-902 at the time of study termination), > 4 weeks since last dose of sorafenib, unless discussed with Sponsor. •
2. If female, pregnant or lactating.
3. Sexually active male and pre-menopausal female subjects (and their partners) unless they agree to use adequate contraceptive measures, while on study and for 45 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. Highly effective birth control includes (a) IUD plus one barrier method; (b) oral, implantable or injectable contraceptive plus one barrier method; or (c) 2 barrier methods. Effective barrier methods are male or female condoms, diaphragms, and spermicides (creams or gels that contain a chemical to kill sperm).
4. Uncontrolled hypertension: systolic blood pressure > 140 mmHg or diastolic blood pressure >90 mmHg documented on 2 consecutive measurements taken at least 24 hours apart.
5. Unhealed wounds (including active peptic ulcers).
6. Serious/active infection or infection requiring parenteral antibiotics.
7. Life-threatening illness or organ system dysfunction compromising safety evaluation.
8. Psychiatric disorder, altered mental status precluding informed consent or necessary testing.
9. Inability to comply with protocol requirements.
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2009-013407-66-NL |
| CCMO | NL30230.078.11 |