An Open-Label Study of QD Oral Administration of Tivozanib (AV-951) in Subjects With Non-Small Cell Lung Cancer (NSCLC)

NCT00826878 | Completed Phase 1

• 1 other identifier: AV-951-08-105
• Study Type: interventional
• Target: 17
• Locations: 1 country
• Sites: 3

Brief Summary

This is a standard Phase 1b and 2a, multi-center, study design that will examine the safety, tolerability, and maximum tolerated dose of tivozanib (AV-951) with this dosing schedule, as well as overall response rate of tivozanib (AV-951) administration in NSCLC.

Conditions

Carcinoma, Non-Small-Cell Lung

Keywords

tivozanib; AV-951

Outcome Measures

Primary Outcomes (2)

• Ph1b: To determine the safety, tolerability, and MTD of tivozanib (AV-951) administered orally QD in subjects with NSCLC

  4 weeks (1 cycle)

• Ph2a: To determine the ORR of tivozanib (AV-951) administered orally once daily in subjects with NSCLC with no prior anti-angiogenic therapy

  8 weeks (2 cycles)

Secondary Outcomes (4)

• Ph1b: To evaluate the PK of tivozanib (AV-951) administered orally QD

  8 weeks (2 cycles)

• Ph1b: To evaluate the preliminary antineoplastic activity of tivozanib (AV-951) administered orally QD

  8 weeks (2 cycles)

• Ph2a: To determine the duration of complete and partial responses and time to disease progression (TTP) for subjects treated with tivozanib (AV-951)

  8 weeks (2 cycles)

• Ph2a: To determine the safety and tolerability of tivozanib (AV-951) administered orally once a day

  4 weeks (1 cycle)

Study Arms (1)

Tivozanib (AV-951)

EXPERIMENTAL

Drug: Tivozanib (AV-951)

Interventions

Tivozanib (AV-951) DRUG

Subjects will receive 1.0 or 1.5 mg tivozanib (AV-951) once daily continuously beginning on Day 1 for 4 weeks. One cycle will be defined as 4 weeks of treatment. Cycles will be repeated every 4 weeks in the absence of disease progression or unacceptable toxicity. Minimum of 8 weeks (2 consecutive dosing cycles), if tolerated.

Tivozanib (AV-951)

Eligibility Criteria

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

You may qualify if:

• Age 18 years or older, of either sex and of any race.
• Histologically or cytologically confirmed NSCL.
• Stage IIIB (with malignant pleural effusion) or stage IV or recurrent disease.
• Subjects that have recurred or progressed following standard therapy or failed standard therapy; or subjects that are not candidates for or unwilling to undergo standard therapy.
• Disease that is currently not amenable to curative surgical intervention, due to either non-resectability of the tumor or medical contraindications.
• Prior VEGF directed therapy
• Prior chemotherapy
• At least 4 weeks since prior immunotherapy (eg, IL-2, IFN, etc.) or biological therapy (eg, MABs) prior to the first dose of study drug.
• At least 1 week since prior treatment with warfarin, acenocoumarol, fenprocoumon, or similar agents.
• At least 4 weeks since prior systemic hormonal therapy.
• At least 2 weeks since prior use of herbal preparations/supplements.
• At least 2 weeks since prior treatment with CYP3A4 inducers or inhibitors.
• At least 2 weeks since prior radiotherapy to ≤25% of bone marrow, or at least 4 weeks since prior radiotherapy to \> 25% of bone marrow.
• Measurable or evaluable disease; subjects enrolled in the Phase 2a study must have measurable disease by RECIST criteria.
• ECOG performance 0-1 and life expectancy ≥ 3 months.

You may not qualify if:

• Subjects with central lung lesions involving major blood vessels.
• Primary CNS malignancies or symptomatic CNS metastases; subjects with previously treated brain metastasis will be allowed if the brain metastasis have been stable without steroid treatment for at least 3 months following prior treatment (radiotherapy or surgery).
• Hematologic malignancies (including leukemia in any form, lymphoma, and multiple myeloma).
• Hematologic abnormalities:
• Serum chemistry abnormalities:
• Significant cardiovascular disease
• Subjects with delayed healing of wounds, active gastric ulcers, or unhealed bone fractures.
• Serious/active infection or infection requiring parenteral antibiotics.
• Inadequate recovery from any prior surgical procedure or major surgical procedure within 6 weeks prior to administration of first dose of study drug.
• Inability to comply with protocol requirements.
• History of ≥ Grade 2 hemoptysis within 6 months prior to administration of first dose of study drug; ongoing bleeding (hemoptysis, hematemesis, hematochezia or melena) or history of clinically significant bleeding within 6 months prior to administration of first dose of study drug.
• Cerebrovascular accident within 12 months prior to administration of first dose of study drug, or peripheral vascular disease with claudication on walking less than 1 block.
• Deep venous thrombosis or pulmonary embolus within 6 months prior to administration of first dose of study drug.
• Subjects with a "currently active" second primary malignancy other than non-melanoma skin cancers or nonmetastatic prostate cancer. Subjects are not considered to have a "currently active" malignancy if they have completed anti-cancer therapy and have been disease free for \>2 years.
• If female, pregnant or lactating.

Sponsors & Collaborators

• AVEO Pharmaceuticals, Inc.: lead

Study Sites (3)

Georgetown University

Washington D.C., District of Columbia, 20007, United States

Location

Kansas University Medical Center

Kansas City, Kansas, 66160, United States

Location

Memorial Sloan-Kettering

New York, New York, 10021, United States

Location

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

tivozanib

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Study Officials

• Jaroslaw Jac, M.D.

  AVEO Pharmaceuticals, Inc.

  STUDY DIRECTOR

• Jimmy Hwang, MD

  Georgetown University

  PRINCIPAL INVESTIGATOR

• Chao Huang, MD

  University of Kansas

  PRINCIPAL INVESTIGATOR

• Naiyer Rizvi, MD

  Memorial Sloan Kettering Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: January 21, 2009
• First Posted: January 22, 2009
• Study Start: January 1, 2009
• Primary Completion: March 1, 2011
• Study Completion: May 1, 2011
• Last Updated: June 28, 2012

Record last verified: 2012-06

Locations

US (3)