A Phase II Study of Tivozanib in Patients With Metastatic and Non-resectable Soft Tissue Sarcomas

NCT01782313 | Completed Phase 2 Results DMC

• 3 other identifiers: NU 12S02NCI-2012-03188STU00073826
• Study Type: interventional
• Target: 58
• Locations: 1 country
• Sites: 5

Brief Summary

This study is for patients who have been diagnosed with soft tissue sarcoma that has spread (metastasized) or that is not eligible for removal by surgery. The purpose of this study is to determine how soft tissue sarcomas respond to treatment with an investigational drug called tivozanib. In some lab and clinical studies, tivozanib has been shown to interfere with the growth of some types of tumors. The study will also evaluate how safe the study treatment is by observing how many and what kind of adverse events (side effects) participants experience.

Conditions

Recurrent Adult Soft Tissue Sarcoma; Stage III Adult Soft Tissue Sarcoma; Stage IV Adult Soft Tissue Sarcoma

Outcome Measures

Primary Outcomes (1)

• Percentage of Patients With Progression-free Survival at 16 Weeks.

  Progression-free survival from study disease will be evaluated using Response Evaluation Criteria in Solid Tumors (RECIST) Committee, version 1.1 assessed using imaging scans (CT or MRI) and clinical assessment following 16 weeks of treatment. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions", or similar definition as accurate and appropriate.

  At 16 weeks of treatment.

Secondary Outcomes (5)

• Overall Response Rate Defined as Complete Response and Partial Response.

  Every 2 cycles (8 weeks) up to 2 years

• Clinical Benefit Rate as Defined by Complete Response, Partial Response and Stable Disease.

  Every 2 cycles (8 weeks) up to 2 years

• Overall Survival up to 2 Years Beyond Progression

  Time from the first dose of study treatment up to 2 years beyond disease progression

• Number of Patients With 0-3 VEGFR1 and VEGFR2 Protein Expression and Time in Days on Treatment

  Tissue collected during screening process, prior to first treatment and response measured until 350 days.

• Treatment Toxicity as Measured by Adverse Events Experienced While on Treatment During Systematic Assessment.

  After every 4 weeks (1 cycle) until treatment discontinuation and up to a maximum of 2 years and 10 months.

Study Arms (1)

Treatment (tivozanib)

EXPERIMENTAL

Patients receive tivozanib PO daily on days 1-21. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Drug: tivozanib; Other: laboratory biomarker analysis

Interventions

tivozanib DRUG

Given PO

Also known as: AV-951, oral VEGF receptor tyrosine kinase inhibitor AV-951

Treatment (tivozanib)

laboratory biomarker analysis OTHER

Correlative studies

Treatment (tivozanib)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients must have histologically or cytologically confirmed sarcoma of soft tissue
• Patients must have metastatic and/or locally advanced or locally recurrent disease
• Patients must have measurable disease within 4 weeks prior to registration by RECIST 1.1, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) as \>= 20 mm with conventional techniques or as \>= 10 mm with spiral computed tomography (CT) scan; tumor lesions that are situated in a previously irradiated area may be considered measurable for the purposes of this study only if there is evidence of growth of the area following a course of irradiation that cannot be attributed to necrosis or bleeding into the tumor
• Patients must have had a minimum of 1 and a maximum of 4 prior chemotherapy regimens for recurrent/metastatic disease (it will be up to the treating investigator to define what constitutes a "regimen" in each case); the last dose of systemic therapy (include tyrosine kinase inhibitors) must have been given at least 4 weeks prior to initiation of therapy; patients receiving BCNU or mitomycin C must have received their last dose of such therapy at least 6 weeks prior to initiation of therapy
• Patients with brain metastasis that have been treated with definitive surgery or radiation and have been clinically stable for 3 months following the procedure with no neurological signs or symptoms and no requirement for systemic glucocorticoids are eligible for study
• Patients must exhibit an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
• Absolute neutrophil count \>= 1.5 x 10\^9/l
• Platelets \>= 75 x 10\^9/l
• Total bilirubin =\< 1.5 x upper limit of normal (ULN) (except for patients with known Gilbert Syndrome)
• Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase \[SGOT\])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) =\< 2.5 x institutional ULN
• Serum creatinine =\< 1.5 x ULN
• If urine protein:creatinine (UPC) \>= 1, then a 24-hour urine protein must be assessed; patients must have a 24-hour urine protein value \< 1g to be eligible
• Patients must not have current evidence of another malignancy; there are no restrictions regarding prior history of malignancy
• If female and of childbearing potential, documentation of negative pregnancy test is required within 7 days prior to first dose; sexually active males and females of childbearing potential must agree to use adequate contraceptive measures, while on study and for 30 days after the last dose of study drug; all subjects (and their partners) must agree to use a highly effective method of contraception; effective birth control includes (a) intrauterine device (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

You may not qualify if:

• Patients with any one of the following sarcoma histological subtypes will not be eligible for participation: alveolar soft-part sarcoma, chondrosarcoma, dermatofibrosarcoma, Ewing sarcoma, gastrointestinal stromal tumor (GIST), Kaposi sarcoma, mixed mesodermal tumor/carcinosarcoma, osteosarcoma, and low grade (grade 1) sarcomas; NOTE: Myxoid liposarcoma with t(12;16) or t(22;22) is permitted; rhabdomyosarcoma (Embryonal, Alveolar, pleomorphic), interdigitating dendritic sarcoma, giant cell tumor of bone
• Patients who have had major surgery within 21 days or those who have not recovered from adverse events associated with surgery to =\< grade 1 will not be eligible for participation; excluded from such considerations are surgical changes not expected to improve, e.g. removal of muscle tissue; patients may be on replacement glucocorticoids for pre-existing glucocorticoid deficiency (e.g. Addison's disease)
• Patients receiving any other investigational agents will not be eligible for participation
• Patients with a history of allergic reactions attributed to compounds of similar chemical or biologic composition to tivozanib will not be eligible for participation
• Patients with serious and/or unstable pre-existing medical, psychiatric, or other conditions that could interfere with safety, provision of informed consent, or compliance to study procedures and requirements will not be eligible for participation, including but not limited to:
• Uncontrolled intercurrent illness
• Ongoing or active infection including HIV, active hepatitis B or C)
• Symptomatic congestive heart failure
• Unstable angina pectoris
• Cardiac arrhythmia
• Psychiatric illness/social situations that would limit compliance with study requirements will not be eligible for participation
• Pregnant women and women who are breast-feeding will not be eligible for participation
• Patients with a history or clinical evidence of central nervous system (CNS) metastases or leptomeningeal carcinomatosis will not be eligible for participation; NOTE: Individuals who have previously-treated CNS metastases, are asymptomatic, and have had no requirement for steroids or anti-seizure medications for 3 months prior to first dose of study drug are the exception; screening with CNS imaging studies such as CT or magnetic resonance imaging (MRI) is required only if clinically indicated or if the subject has a history of CNS metastases
• Patients with clinically significant gastrointestinal (GI) abnormalities that may increase the risk for GI bleeding will not be eligible for participation; these include, but are not limited to:
• Active peptic ulcer disease

Sponsors & Collaborators

• Northwestern University: lead
• AVEO Pharmaceuticals, Inc.: collaborator

Study Sites (5)

Northwestern University

Chicago, Illinois, 60611, United States

Location

University of Iowa

Iowa City, Iowa, 52246, United States

Location

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

Washington University

St Louis, Missouri, 63110, United States

Location

University of Wisconsin

Madison, Wisconsin, 53792, United States

Location

Related Publications (1)

• Agulnik M, Costa RLB, Milhem M, Rademaker AW, Prunder BC, Daniels D, Rhodes BT, Humphreys C, Abbinanti S, Nye L, Cehic R, Polish A, Vintilescu C, McFarland T, Skubitz K, Robinson S, Okuno S, Van Tine BA. A phase II study of tivozanib in patients with metastatic and nonresectable soft-tissue sarcomas. Ann Oncol. 2017 Jan 1;28(1):121-127. doi: 10.1093/annonc/mdw444.

  PMID: 27771610 DERIVED

MeSH Terms

Conditions

Sarcoma

Interventions

tivozanib

Condition Hierarchy (Ancestors)

Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms

Results Point of Contact

• Title: Mark Agulnik, MD
• Organization: Northwestern University

magulnik@nm.org

312 695 6182

Study Officials

• Mark Agulnik, MD

  Northwestern University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: January 30, 2013
• First Posted: February 1, 2013
• Study Start: March 6, 2013
• Primary Completion: May 27, 2015
• Study Completion: December 28, 2016
• Last Updated: September 9, 2019
• Results First Posted: August 21, 2018

Record last verified: 2019-08

Locations

US (5)