Tivozanib in Treating Patients With Liver Cancer That Is Metastatic or Cannot Be Removed by Surgery

NCT01835223 | Completed Phase 1 Results DMC

• 3 other identifiers: I 229112NCI-2013-00756P30CA016056
• Study Type: interventional
• Target: 33
• Locations: 1 country
• Sites: 2

Brief Summary

This phase I/II trial studies the side effects and best dose of tivozanib and to see how well it works in treating patients with liver cancer that has spread to other parts of the body or cannot be removed by surgery. Tivozanib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

Conditions

Advanced Adult Hepatocellular Carcinoma; Non-Resectable Hepatocellular Carcinoma

Outcome Measures

Primary Outcomes (1)

• PFS, Assessed Using Standard RECIST Criteria

  Will be descriptively analyzed using standard Kaplan-Meier estimation along with the corresponding descriptive statistics and 95% confidence intervals.

  24 weeks

Secondary Outcomes (3)

• Clinical Benefit Rate (CR, PR, and SD) by RECIST

  Up to 3 years

• Incidence of Adverse Events and Toxicities, Assessed Using National Cancer Institute Common Terminology Criteria for Adverse Events Version 4

  Up to 3 years

• Overall Survival Rate

  Up to 3 years

Other Outcomes (3)

• AFP Response

  Up to 3 years

• Antiviral Effects (if Any in Those With HBV or HCV Associated HCC)

  Up to 3 years

• Drug Exposure, as Assessed by Steady State PK

  Up to 3 years

Study Arms (2)

Treatment (tivozanib - 1 mg)

EXPERIMENTAL

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

Drug: Tivozanib (1mg)

Treatment (tivozanib - 1.5 mg)

EXPERIMENTAL

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

Drug: Tivozanib (1.5mg)

Interventions

Tivozanib (1mg) DRUG

Given PO

Also known as: AV-951, TIVOZANIB

Treatment (tivozanib - 1 mg)

Tivozanib (1.5mg) DRUG

Given PO

Also known as: AV-951, TIVOZANIB

Treatment (tivozanib - 1.5 mg)

Eligibility Criteria

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

You may qualify if:

• Advanced staged HCC (unresectable and not amenable to local or regional therapy; or metastatic HCC); the diagnosis of HCC should be based on at least one of the following:
• Magnetic resonance imaging (MRI) or computed tomography (CT) consistent with liver cirrhosis AND at least one solid liver lesion measuring \>= 2 cm, with characteristics arterial enhancement and venous washout regardless of alpha-fetoprotein (AFP) levels
• AFP \>= 400 ng/mL AND evidence of at least one solid liver lesion \>= 2 cm regardless of specific imaging characteristics on CT or MRI
• Histological/cytology biopsy confirming HCC
• Patients must have measurable disease per RECIST 1.1 criteria defined as at least one lesion that can be accurately measured in at least one dimension, and that has not been the target of local or regional therapy including transarterial chemoembolization, intra-arterial chemotherapy, ethanol or radiofrequency ablation
• Life expectancy of greater than 3 months
• Child-Pugh liver function class A
• Aspartate aminotransferase (AST) =\< 5 x institutional upper limits of normal (ULN)
• Total bilirubin =\< 3 mg/dL
• International normalized ratio (INR) =\< 2.0 (unless due to therapeutic warfarin use)
• Serum albumin \> 2.8 g/dL
• Creatinine =\< 1.5 x institutional ULN
• Absolute neutrophil count (ANC) \>= 1200/mm\^3
• Platelets \>= 60,000/mm\^3
• Hemoglobin (Hgb) \>= 8.5 g/dL

You may not qualify if:

• Patients who have had prior anti-angiogenic therapy, including but not limited to sorafenib, brivanib, bevacizumab, or sunitinib
• Patients who have had any prior line of systemic therapy including cytotoxic agents or molecularly targeted agents for advanced/unresectable disease; any number of prior regional therapies with transarterial chemoembolization (TACE), brachytherapy with yttrium-90 microsphere, intra-arterial chemotherapy, surgery, or ablative therapy are allowed
• Prior liver transplantation and on immunosuppression
• Known symptomatic or uncontrolled brain metastases or epidural disease
• Patient has a corrected QT interval (QTcF) \> 500 ms at screening
• The patient is unable to swallow pills or diagnosed with a gastrointestinal disorder that are likely to interfere with the absorption of the study drug or with the patient's ability to take regular oral medication
• The patient is pregnant or breastfeeding
• Patients with second primary cancer (except adequately treated nonmelanoma skin cancer, curatively treated in-situ carcinoma of the cervix or superficial bladder cancer, or other solid tumors including lymphoma without bone marrow involvement curatively treated with no evidence of disease for \>= 5 years)
• The patient has a previously-identified allergy or hypersensitivity to components of the study treatment formulation
• Patients receiving any medications or substances that are strong inducers of cytochrome P450, family 3, subfamily A, polypeptide 4 (CYP3A4) are ineligible; moderate inducers of CYP3A4 should be used with caution
• Urine protein: creatinine ratio \> 1

Sponsors & Collaborators

• Roswell Park Cancer Institute: lead
• National Comprehensive Cancer Network: collaborator
• AVEO Pharmaceuticals, Inc.: collaborator
• National Cancer Institute (NCI): collaborator

Study Sites (2)

Roswell Park Cancer Institute

Buffalo, New York, 14263, United States

Location

Case Western Reserve University

Cleveland, Ohio, 44106, United States

Location

Related Publications (4)

• Kalathil SG, Thanavala Y. Natural Killer Cells and T Cells in Hepatocellular Carcinoma and Viral Hepatitis: Current Status and Perspectives for Future Immunotherapeutic Approaches. Cells. 2021 May 28;10(6):1332. doi: 10.3390/cells10061332.

  PMID: 34071188 DERIVED

• Kalathil SG, Thanavala Y. Importance of myeloid derived suppressor cells in cancer from a biomarker perspective. Cell Immunol. 2021 Mar;361:104280. doi: 10.1016/j.cellimm.2020.104280. Epub 2020 Dec 31.

  PMID: 33445053 DERIVED

• Kalathil SG, Wang K, Hutson A, Iyer R, Thanavala Y. Tivozanib mediated inhibition of c-Kit/SCF signaling on Tregs and MDSCs and reversal of tumor induced immune suppression correlates with survival of HCC patients. Oncoimmunology. 2020 Sep 30;9(1):1824863. doi: 10.1080/2162402X.2020.1824863.

  PMID: 33101775 DERIVED

• Fountzilas C, Gupta M, Lee S, Krishnamurthi S, Estfan B, Wang K, Attwood K, Wilton J, Bies R, Bshara W, Iyer R. A multicentre phase 1b/2 study of tivozanib in patients with advanced inoperable hepatocellular carcinoma. Br J Cancer. 2020 Mar;122(7):963-970. doi: 10.1038/s41416-020-0737-6. Epub 2020 Feb 10.

  PMID: 32037403 DERIVED

MeSH Terms

Interventions

tivozanib

Results Point of Contact

• Title: Katy Wang, Statistician, M.A.
• Organization: Roswell Park Cancer Institute

katy.wang@roswellpark.org

716-845-1300

Study Officials

• Renuka Iyer

  Roswell Park Cancer Institute

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 15, 2013
• First Posted: April 18, 2013
• Study Start: July 11, 2013
• Primary Completion: December 24, 2018
• Study Completion: November 8, 2019
• Last Updated: October 28, 2020
• Results First Posted: October 28, 2020

Record last verified: 2020-10

Locations

US (2)