A Rollover Protocol to Allow Continued Access to Tivozanib (AV 951) for Subjects Enrolled in Other Tivozanib Protocols

Study Overview
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Brief Summary
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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
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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.

Official Title
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A Rollover Protocol to Allow Continued Access to Tivozanib (AV 951) for Subjects Enrolled in Other Tivozanib Protocols

Conditions
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Solid Tumors

Intervention / Treatment
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* Drug: Tivozanib + paclitaxel
* Drug: Tivozanib + temsirolimus
* Drug: Tivozanib
* Drug: Tivozanib (AV-951)
* Drug: Tivozanib + capecitabine
* Drug: Tivo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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. If female and of childbearing potential, documentation of negative pregnancy test prior to enrollment. Ability to give written informed consent. Exclusion Criteria: > 4 weeks since discontinuation of tivozanib treatment on a previous protocol If female, pregnant or lactating 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.) 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. 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. Unhealed wounds (including active peptic ulcers) Serious/active infection or infection requiring parenteral antibiotics Life-threatening illness or organ system dysfunction compromising safety evaluation Psychiatric disorder, altered mental status precluding informed consent or necessary testing Inability to comply with protocol requirements

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: tivozanib renal cell carcinoma (RCC)<br>Subjects who participated in a Phase 2 monotherapy study in RCC and showed tolerability and clinical benefit will be allowed access to tivozanib (AV-951). | Drug: Tivozanib<br>* Subjects will receive 1.0 or 1.5 mg tivozanib (AV-951) capsules once daily for 3 weeks, followed by 1 week off.<br>* Other names: Tivo (AV951);|
| Experimental: tivozanib + temsirolimus<br>Subjects who participated in a Phase 1b study and showed tolerability and clinical benefit will be allowed continued access to the tivozanib (AV-951) + temsirolimus combination. | Drug: Tivozanib + temsirolimus<br>* 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.<br>* Other names: Tivo (AV-951) + temsirolimus;|
| Experimental: tivozanib + paclitaxel<br>Subjects who participated in a Phase 1b study and showed tolerability and clinical benefit will be allowed continued access to the tivozanib (AV-951) + paclitaxel combination. | Drug: Tivozanib + paclitaxel<br>* 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.<br>* Other names: Tivo (AV-951) + paclitaxel;|
| Experimental: tivozanib solid tumors - QTC<br>Subjects who participated in a Phase 1 and showed tolerability and clinical benefit will be allowed continued access to the tivozanib (AV-951). | Drug: Tivozanib (AV-951)<br>* Subjects will receive 1.0 or 1.5 mg tivozanib (AV-951) capsules once daily for 3 weeks, followed by 1 week off.<br>* Other names: Tivo, (AV-951);|
| Experimental: tivozanib + capecitabine<br>After Ph 1b study tolerable to Tivo + Xeloda® | Drug: Tivozanib + capecitabine<br>* 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.<br>* Other names: Tivo, (AV-951) + capecitabine;|
| Experimental: tivozanib Advanced RCC<br>After biomarker study tolerable to Tivo | Drug: Tivo<br>* Subjects will receive 1.5 mg tivozanib once daily beginning on Day 1 for 3 weeks followed by 1 week off treatment.<br>* Other names: Tivo, (AV-951);|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | 24 Months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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tivozanib