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

This study is enrolling participants by invitation only.
Sponsor:
Information provided by (Responsible Party):
AVEO Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier:
NCT01369433
First received: March 4, 2010
Last updated: June 13, 2013
Last verified: June 2013
  Purpose

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).


Condition Intervention
Solid Tumors
Drug: tivozanib (AV-951) + paclitaxel
Drug: tivozanib (AV-951) + temsirolimus
Drug: tivozanib (AV-951)
Drug: tivozanib (AV-951) + capecitabine

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Rollover Protocol to Allow Continued Access to Tivozanib (AV 951) for Subjects Enrolled in Other Tivozanib Protocols

Resource links provided by NLM:


Further study details as provided by AVEO Pharmaceuticals, Inc.:

Primary Outcome Measures:
  • To assess long-term safety and tolerability of tivozanib in subjects who continue on tivozanib, in accordance with the parent protocol. [ Time Frame: 24 Months ] [ Designated as safety issue: Yes ]
    Patients are assessed for safety and tolerability on Day 1 of each cycle via Adverse Event assessments, Study Drug diary, concomitant medications review, blood pressure, hematology and serum chemistry labs, urinalysis with microscopic test as well as disease assessment completed at end of Cycle 2 and every even numbered cycles. All assessments are made in accordance to the protocol of the parent study in which the patient had participated in before enrolling in the AV-951-09-901 rollover study.

  • To determine the duration of response and progression-free survival (PFS) of subjects who continue on tivozanib, in accordance with the parent protocol [ Time Frame: 24 Months ] [ Designated as safety issue: No ]
    All assessments made to determine the duration of response and progression-free survival (PFS) of tivozanib will be determined in accordance to the protocol of the parent study in which the patient had participated in before enrolling in the AV-951-09-901 rollover study.


Estimated Enrollment: 200
Study Start Date: June 2010
Estimated Study Completion Date: June 2013
Estimated Primary Completion Date: June 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: tivozanib (AV-951) RCC
Subjects who participated in a Phase 2 monotherapy study in RCC and showed tolerablity and clinical benefit will be allowed access to tivozanib (AV-951).
Drug: tivozanib (AV-951)
Subjects will receive 1.0 or 1.5 mg tivozanib (AV-951) capsules once daily for 3 weeks, followed by 1 week off.
Experimental: tivozanib (AV-951) + temsirolimus
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 (AV-951) + 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.
Experimental: tivozanib (AV-951) + paclitaxel
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 (AV-951) + paclitaxel
Subjects will continue to receive 0.5 mg, 1.0 mg, or 1.5 mg of tivozanib (AV-951) 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 (AV-951) 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.
Experimental: tivozanib (AV-951) solid tumors - QTC
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)
Subjects will receive 1.0 or 1.5 mg tivozanib (AV-951) capsules once daily for 3 weeks, followed by 1 week off.
Experimental: tivozanib (AV-951) + capecitabine - solid tumors
Subjects who participated in a Phase 1b study showed tolerability and clinical benefit will be allowed continued access to the tivozanib (AV-951) in combination with Capecitabine (Xeloda®) in Subjects with Advanced Solid Tumors
Drug: tivozanib (AV-951) + 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.
Experimental: tivozanib (AV-951) Advanced RCC
Subject who participated in a Phase 2 Biomarker study and showed tolerability and clinical benefit will be alloted continued aces to the tivozanib.
Drug: tivozanib (AV-951)
Subjects will receive 1.5 mg tivozanib once daily beginning on Day 1 for 3 weeks followed by 1 week off treatment.

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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) 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.)
  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 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01369433

  Show 49 Study Locations
Sponsors and Collaborators
AVEO Pharmaceuticals, Inc.
Investigators
Study Director: Anna Berkenblit, MD AVEO Pharmaceuticals, Inc.
  More Information

Additional Information:
No publications provided

Responsible Party: AVEO Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier: NCT01369433     History of Changes
Other Study ID Numbers: AV-951-09-901
Study First Received: March 4, 2010
Last Updated: June 13, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by AVEO Pharmaceuticals, Inc.:
tivozanib

Additional relevant MeSH terms:
Capecitabine
Everolimus
Paclitaxel
Sirolimus
Anti-Bacterial Agents
Anti-Infective Agents
Antibiotics, Antineoplastic
Antifungal Agents
Antimetabolites
Antimetabolites, Antineoplastic
Antimitotic Agents
Antineoplastic Agents
Antineoplastic Agents, Phytogenic
Immunologic Factors
Immunosuppressive Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses
Tubulin Modulators

ClinicalTrials.gov processed this record on November 23, 2014