A Phase 1b, Open-Label, Dose-Finding Study to Evaluate the Safety of Tivozanib (AV-951) in Combination With Temsirolimus in Subjects With Metastatic Renal Cell Carcinoma

NCT00563147 | Completed Phase 1

• 1 other identifier: AV-951-07-102
• Study Type: interventional
• Target: 28
• Locations: 1 country
• Sites: 5

Brief Summary

The purpose of this study is to test the safety and tolerability of tivozanib (AV-951) and Torisel™ given in combination for renal cell cancer. The study will also assess the effects of the combination of tivozanib (AV-951) and Torisel™ on the tumor. Tivozanib (AV-951) is a VEGF-receptor tyrosine kinase inhibitor, and may stop the growth of tumor cells by blocking blood flow to the tumor. Temsirolimus is an mTOR inhibitor which is approved for the treatment of advanced renal cell carcinoma.

Conditions

Renal Cell Carcinoma

Keywords

tivozanib; AV-951

Outcome Measures

Primary Outcomes (1)

• To determine the safety and tolerability of tivozanib (AV-951) when given in combination with temsirolimus

  4 weeks (1 cycle)

Secondary Outcomes (4)

• To characterize the pharmacokinetic profile of tivozanib (AV-951) and temsirolimus when administered in combination

  8 weeks (2 cycles)

• To evaluate the antineoplastic activity of tivozanib (AV-951) and temsirolimus when administered in combination

  8 weeks (2 cycles)

• To evaluate the effect of tivozanib (AV-951) and temsirolimus on global and targeted gene expression patterns

  8 weeks (2 cycles)

• To determine the maximum tolerated dose (MTD) of tivozanib (AV-951) when administered in combination with temsirolimus

  4 weeks (1 cycle)

Study Arms (1)

A

EXPERIMENTAL

tivozanib (AV-951) plus temsirolimus

Drug: tivozanib (AV-951) plus temsirolimus

Interventions

tivozanib (AV-951) plus temsirolimus DRUG

ascending doses of tivozanib (AV-951) capsules administered orally for 21 days with discontinuation for 7 days; ascending doses of temsirolimus administered intravenously every 7 days

Also known as: Torisel (temsirolimus)

A

Eligibility Criteria

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

You may qualify if:

• ≥ 18-year-old males or females
• Histologically confirmed renal cell carcinoma with a clear cell component
• Documented progressive disease
• Measurable disease by RECIST criteria
• No more than 1 prior VEGF receptor targeted therapy; no prior treatment with temsirolimus or other drugs targeting the mTOR pathway
• Karnofsky performance status \> 70%; life expectancy ≥ 3 months
• Ability to give written informed consent

You may not qualify if:

• Known hypersensitivity to temsirolimus or its metabolites (including sirolimus), polysorbate 80, or to any other component of the temsirolimus formulation
• Primary CNS malignancies; active CNS metastases
• Hematologic malignancies (including leukemia in any form, lymphoma, and multiple myeloma)
• Any of the following hematologic abnormalities:
• Hemoglobin \< 9.0 g/dL
• ANC \< 1500 per mm3
• Platelet count \< 100,000 per mm3
• Any of the following serum chemistry abnormalities:
• Fasting serum cholesterol \> 350 mg/dL
• Fasting triglycerides \> 400 mg/dL
• Total bilirubin \> 1.5 × ULN
• AST or ALT \> 2.5 × ULN (or \> 5 x ULN in subjects with liver metastasis)
• Serum albumin \< 3.0 g/dL
• Creatine \> 1.5 × ULN (or calculated CLCR \<50 mL/min/1.73 m2)
• Proteinuria \> 2.5 g/24 hours or 3+ with urine dipstick

Sponsors & Collaborators

• AVEO Pharmaceuticals, Inc.: lead

Study Sites (5)

UCLA Jonsson Comprehensive Cancer Center

Los Angeles, California, 90095, United States

Location

Stanford University

Stanford, California, 94305, United States

Location

H. Lee Moffitt Cancer Center

Tampa, Florida, 33612, United States

Location

Nebraska Methodist Hospital

Omaha, Nebraska, 68114, United States

Location

The Methodist Hospital Research Institute

Houston, Texas, 77030, United States

Location

Related Publications (1)

• Fishman MN, Srinivas S, Hauke RJ, Amato RJ, Esteves B, Cotreau MM, Strahs AL, Slichenmyer WJ, Bhargava P, Kabbinavar FF. Phase Ib study of tivozanib (AV-951) in combination with temsirolimus in patients with renal cell carcinoma. Eur J Cancer. 2013 Sep;49(13):2841-50. doi: 10.1016/j.ejca.2013.04.019. Epub 2013 May 28.

  PMID: 23726267 DERIVED

MeSH Terms

Conditions

Carcinoma, Renal Cell

Interventions

tivozanib; temsirolimus

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Kidney Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Kidney Diseases; Urologic Diseases; Male Urogenital Diseases

Study Officials

• Joshua Zhang, M.D.

  AVEO Pharmaceuticals

  STUDY DIRECTOR

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: November 21, 2007
• First Posted: November 26, 2007
• Study Start: November 1, 2007
• Primary Completion: November 1, 2010
• Study Completion: February 1, 2011
• Last Updated: October 4, 2011

Record last verified: 2011-09

Locations

US (5)