Solid Tumors
Conditions
Keywords
tivozanib
Brief summary
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. Subjects will be seen by the investigator every 4 weeks (± 5 days). Adverse events and blood pressure will be recorded. At the beginning of Cycle 1 and at the beginning of every odd-numbered cycle (Cycle 3, Cycle 5, etc), clinical laboratory values will be recorded. CT scans to assess disease will be performed at the end of even-numbered cycles (Cycle 2, Cycle 4, etc).
Detailed description
This is an open-label multi-center, multi-national rollover protocol 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. Enrollment to this protocol will remain open to subjects who participate in current and future protocols with tivozanib. The end of the study is the last treatment visit of the last subject at the last site. Enrollment in this protocol will continue until 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 make every effort to assist the subject in obtaining commercially available tivozanib. This rollover protocol will be open to eligible subjects on current and future protocols with tivozanib. The number of subjects who will enroll is dependent upon the number of subjects enrolled in tivozanib protocols that tolerate the drug, display clinical benefits, and are willing to participate.
Interventions
DRUGTivozanib + paclitaxel
Subjects will continue to receive 0.5 mg, 1.0 mg, or 1.5 mg of tivozanib once daily for 3 weeks beginning on Day 1, followed by 1 week off treatment. On days when paclitaxel and tivozanib (AV-951) are co-administered, tivozanib will be administered immediately following the end of the paclitaxel infusion. All subjects will continue to receive IV paclitaxel 90 mg/m2, administered over 1 hour once a week for 3 weeks, followed by 1 week off.
DRUGTivozanib + temsirolimus
Subjects will receive 0.5 mg, 1.0 mg or 1.5 mg of tivozanib (AV-951) once daily for 3 weeks, followed by 1 week off. On days when tivozanib (AV-951) and temsirolimus are co-administered, tivozanib (AV-951) will be administered immediately following temsirolimus infusion. Subjects will receive 15 mg or 25 mg temsirolimus IV once weekly.
DRUGTivozanib
Subjects will receive 1.0 or 1.5 mg tivozanib (AV-951) capsules once daily for 3 weeks, followed by 1 week off.
Subjects will receive 1.0 or 1.5 mg tivozanib (AV-951) capsules once daily for 3 weeks, followed by 1 week off.
DRUGTivozanib + capecitabine
Subjects will receive 1.5 mg of tivozanib once daily for 2 weeks beginning on Day 1, followed by 1 week off. Subjects will receive Capecitabine (Xeloda®) 825 mg/m2 or 1000 mg/m² or 1250 mg/m² oral twice daily. Subjects will receive capecitabine twice daily for 2 weeks beginning on Day 1, followed by 1 week off.
DRUGTivo
Subjects will receive 1.5 mg tivozanib once daily beginning on Day 1 for 3 weeks followed by 1 week off treatment.
Sponsors
AVEO Pharmaceuticals, Inc.
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. The subject must have received tivozanib 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. 2. If female and of childbearing potential, documentation of negative pregnancy test prior to enrollment. 3. Ability to give written informed consent.
Exclusion criteria
1. \> 4 weeks since discontinuation of tivozanib treatment on a previous protocol 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 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. Highly 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.) 4. Uncontrolled hypertension: systolic blood pressure \> 140 mmHg or diastolic blood pressure \>90 mmHg on 2 or more antihypertensive medications, documented on 2 consecutive measurements taken at least 24 hours apart. 5. 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 please refer to Section 6.3 for allowed steroid maintenance therapy. 6. Unhealed wounds (including active peptic ulcers) 7. Serious/active infection or infection requiring parenteral antibiotics 8. Life-threatening illness or organ system dysfunction compromising safety evaluation 9. Psychiatric disorder, altered mental status precluding informed consent or necessary testing 10. Inability to comply with protocol requirements
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Subjects With Adverse Events (AEs) and Serious AEs | 24 Months | Safety and tolerability will be assessed in accordance to the protocol of the parent study in which the subjects had participated, before enrolling in the AV-951-09-901 rollover study. |
Countries
Canada, India, Netherlands, Russia, Ukraine, United States
Participant flow
Recruitment details
Subjects who met all the inclusion and none of the exclusion criteria were enrolled in the study.
Pre-assignment details
All subjects underwent inclusion and exclusion criteria assessment and all eligible subjects signed the informed consent before undergoing any study related procedures. All the study assessments were performed as per the schedule of assessment.
Participants by arm
| Arm | Count |
|---|---|
| Monotherapy Participants received oral tivozanib hydrochloride at the same dose and schedule as during the parent protocol. Studies under monotherapy were AV-951-10-112, AV-951-07-201, AV-951-110-202, AV-951-12-205, and AV-951-09-902. Drug: Tivozanib hydrochloride. | 209 |
| Combination Therapy Participants who were receiving tivozanib hydrochloride combination, continued the combination therapy, as long as it was tolerated, at the same dose and schedule as in the parent protocol. Eligible participants who received sorafenib in Parent Study AV-951-09-902 at the time of study termination and who rolled into Study AV-951-09-901 began tivozanib hydrochloride at a dose of 1.5 mg/day. Studies under combination therapy were AV-951-07-102, AV-951-07-103, AV-951-08-104, AV-951-10-114, and AV-951-12-204. Combination Drugs: Tivozanib hydrochloride + temsirolimus, Tivozanib hydrochloride + paclitaxel, and Tivozanib hydrochloride + capecitabine. | 16 |
| Total | 225 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 31 | 1 |
| Overall Study | Death | 5 | 0 |
| Overall Study | Investigator discretion | 6 | 1 |
| Overall Study | Lost to Follow-up | 1 | 0 |
| Overall Study | Non-compliance | 1 | 0 |
| Overall Study | Progressive Disease | 92 | 12 |
| Overall Study | Required significant surgical procedure | 1 | 0 |
| Overall Study | Study terminated by Sponsor | 67 | 0 |
| Overall Study | Withdrawal by Subject | 5 | 2 |
Baseline characteristics
| Characteristic | Combination Therapy | Total | Monotherapy |
|---|---|---|---|
| Age, Customized 18 to >= 75 years | 16 participants | 225 participants | 209 participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 3 Participants | 3 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 5 Participants | 5 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 2 Participants | 2 Participants |
| Race (NIH/OMB) White | 16 Participants | 215 Participants | 199 Participants |
| Sex: Female, Male Female | 6 Participants | 86 Participants | 80 Participants |
| Sex: Female, Male Male | 10 Participants | 139 Participants | 129 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 178 / 209 | 16 / 16 |
| serious Total, serious adverse events | 44 / 209 | 5 / 16 |
Outcome results
Primary
Number of Subjects With Adverse Events (AEs) and Serious AEs
Safety and tolerability will be assessed in accordance to the protocol of the parent study in which the subjects had participated, before enrolling in the AV-951-09-901 rollover study.
Time frame: 24 Months
Population: Of the 225 subjects, 209 subjects had monotherapy treatment during their parent study; the remaining subjects (N=16) had combination therapy~* Monotherapy: Studies AV-951-10-112, AV-951-07-201, AV-951-110-202, AV-951-12-205, AV-951-09-902.~* Combination: Studies AV-951-07-102, AV-951-07-103, AV-951-08-104, AV-951-10-114, AV-951-12-204.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Monotherapy | Number of Subjects With Adverse Events (AEs) and Serious AEs | AEs ≥Grade 3 toxicity | 111 Participants |
| Monotherapy | Number of Subjects With Adverse Events (AEs) and Serious AEs | Treatment-related AEs | 159 Participants |
| Monotherapy | Number of Subjects With Adverse Events (AEs) and Serious AEs | AEs-death | 13 Participants |
| Monotherapy | Number of Subjects With Adverse Events (AEs) and Serious AEs | AEs-study drug interruption | 54 Participants |
| Monotherapy | Number of Subjects With Adverse Events (AEs) and Serious AEs | Serious Adverse events (SAEs) | 44 Participants |
| Monotherapy | Number of Subjects With Adverse Events (AEs) and Serious AEs | AEs | 178 Participants |
| Monotherapy | Number of Subjects With Adverse Events (AEs) and Serious AEs | SAEs ≥Grade 3 toxicity | 38 Participants |
| Monotherapy | Number of Subjects With Adverse Events (AEs) and Serious AEs | AEs-study drug dose reduction | 13 Participants |
| Monotherapy | Number of Subjects With Adverse Events (AEs) and Serious AEs | Serious treatment-related AEs | 16 Participants |
| Monotherapy | Number of Subjects With Adverse Events (AEs) and Serious AEs | AEs-discontinuation of study drug | 31 Participants |
| Combination Therapy | Number of Subjects With Adverse Events (AEs) and Serious AEs | Serious treatment-related AEs | 0 Participants |
| Combination Therapy | Number of Subjects With Adverse Events (AEs) and Serious AEs | AEs | 16 Participants |
| Combination Therapy | Number of Subjects With Adverse Events (AEs) and Serious AEs | Treatment-related AEs | 15 Participants |
| Combination Therapy | Number of Subjects With Adverse Events (AEs) and Serious AEs | AEs ≥Grade 3 toxicity | 12 Participants |
| Combination Therapy | Number of Subjects With Adverse Events (AEs) and Serious AEs | AEs-study drug interruption | 6 Participants |
| Combination Therapy | Number of Subjects With Adverse Events (AEs) and Serious AEs | AEs-study drug dose reduction | 0 Participants |
| Combination Therapy | Number of Subjects With Adverse Events (AEs) and Serious AEs | AEs-discontinuation of study drug | 1 Participants |
| Combination Therapy | Number of Subjects With Adverse Events (AEs) and Serious AEs | AEs-death | 1 Participants |
| Combination Therapy | Number of Subjects With Adverse Events (AEs) and Serious AEs | Serious Adverse events (SAEs) | 5 Participants |
| Combination Therapy | Number of Subjects With Adverse Events (AEs) and Serious AEs | SAEs ≥Grade 3 toxicity | 5 Participants |