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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
AVEO Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier:
NCT00826878
First received: January 21, 2009
Last updated: June 27, 2012
Last verified: June 2012
  Purpose

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.


Condition Intervention Phase
Carcinoma, Non-Small-Cell Lung
Drug: Tivozanib (AV-951)
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase 1b/2a Open-Label Study to Evaluate the Safety and Activity of Once Daily Oral Administration of Tivozanib (AV-951) in Subjects With Non-Small Cell Lung Cancer

Resource links provided by NLM:


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

Primary Outcome Measures:
  • Ph1b: To determine the safety, tolerability, and MTD of tivozanib (AV-951) administered orally QD in subjects with NSCLC [ Time Frame: 4 weeks (1 cycle) ] [ Designated as safety issue: Yes ]
  • Ph2a: To determine the ORR of tivozanib (AV-951) administered orally once daily in subjects with NSCLC with no prior anti-angiogenic therapy [ Time Frame: 8 weeks (2 cycles) ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Ph1b: To evaluate the PK of tivozanib (AV-951) administered orally QD [ Time Frame: 8 weeks (2 cycles) ] [ Designated as safety issue: No ]
  • Ph1b: To evaluate the preliminary antineoplastic activity of tivozanib (AV-951) administered orally QD [ Time Frame: 8 weeks (2 cycles) ] [ Designated as safety issue: No ]
  • Ph2a: To determine the duration of complete and partial responses and time to disease progression (TTP) for subjects treated with tivozanib (AV-951) [ Time Frame: 8 weeks (2 cycles) ] [ Designated as safety issue: No ]
  • Ph2a: To determine the safety and tolerability of tivozanib (AV-951) administered orally once a day [ Time Frame: 4 weeks (1 cycle) ] [ Designated as safety issue: Yes ]

Enrollment: 17
Study Start Date: January 2009
Study Completion Date: May 2011
Primary Completion Date: March 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Tivozanib (AV-951) Drug: Tivozanib (AV-951)

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.


Detailed Description:

The Phase 2a portion of the study was not conducted

  Eligibility

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

Inclusion Criteria:

  1. Age 18 years or older, of either sex and of any race.
  2. Histologically or cytologically confirmed NSCL.
  3. Stage IIIB (with malignant pleural effusion) or stage IV or recurrent disease.
  4. 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.
  5. Disease that is currently not amenable to curative surgical intervention, due to either non-resectability of the tumor or medical contraindications.
  6. Prior VEGF directed therapy
  7. Prior chemotherapy
  8. 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.
  9. At least 1 week since prior treatment with warfarin, acenocoumarol, fenprocoumon, or similar agents.
  10. At least 4 weeks since prior systemic hormonal therapy.
  11. At least 2 weeks since prior use of herbal preparations/supplements.
  12. At least 2 weeks since prior treatment with CYP3A4 inducers or inhibitors.
  13. 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.
  14. Measurable or evaluable disease; subjects enrolled in the Phase 2a study must have measurable disease by RECIST criteria.
  15. ECOG performance 0-1 and life expectancy ≥ 3 months.
  16. Ability to give written informed consent.

Exclusion Criteria:

  1. Subjects with central lung lesions involving major blood vessels.
  2. 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).
  3. Hematologic malignancies (including leukemia in any form, lymphoma, and multiple myeloma).
  4. Hematologic abnormalities:
  5. Serum chemistry abnormalities:
  6. Significant cardiovascular disease
  7. Subjects with delayed healing of wounds, active gastric ulcers, or unhealed bone fractures.
  8. Serious/active infection or infection requiring parenteral antibiotics.
  9. Inadequate recovery from any prior surgical procedure or major surgical procedure within 6 weeks prior to administration of first dose of study drug.
  10. Inability to comply with protocol requirements.
  11. 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.
  12. 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.
  13. Deep venous thrombosis or pulmonary embolus within 6 months prior to administration of first dose of study drug.
  14. 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.
  15. If female, pregnant or lactating.
  16. No childbearing potential or the use of effective contraception by all fertile male and female subjects during the study and for 30 days after the last dose of study drug. All subjects must agree to use a highly effective method of contraception (including their partner).
  17. Known concomitant genetic or acquired immune suppression disease such as HIV.
  18. Inadequate recovery from prior antineoplastic therapy.
  19. Life-threatening illness or organ system dysfunction compromising safety evaluation.
  20. Psychiatric disorder, altered mental status precluding informed consent or necessary testing.
  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: NCT00826878

Locations
United States, District of Columbia
Georgetown University
Washington, District of Columbia, United States, 20007
United States, Kansas
Kansas University Medical Center
Kansas City, Kansas, United States, 66160
United States, New York
Memorial Sloan-Kettering
New York, New York, United States, 10021
Sponsors and Collaborators
AVEO Pharmaceuticals, Inc.
Investigators
Study Director: Jaroslaw Jac, M.D. AVEO Pharmaceuticals, Inc.
Principal Investigator: Jimmy Hwang, MD Georgetown University
Principal Investigator: Chao Huang, MD University of Kansas
Principal Investigator: Naiyer Rizvi, MD Memorial Sloan-Kettering Cancer Center
  More Information

No publications provided

Responsible Party: AVEO Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier: NCT00826878     History of Changes
Other Study ID Numbers: AV-951-08-105
Study First Received: January 21, 2009
Last Updated: June 27, 2012
Health Authority: United States: Food and Drug Administration

Keywords provided by AVEO Pharmaceuticals, Inc.:
tivozanib
AV-951

Additional relevant MeSH terms:
Carcinoma, Non-Small-Cell Lung
Carcinoma, Bronchogenic
Bronchial Neoplasms
Lung Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases

ClinicalTrials.gov processed this record on September 30, 2014