A Study of AV-951, an Oral VEGF Receptor Tyrosine Kinase Inhibitor, in the Treatment of Renal Cell Carcinoma - Full Text View

Sponsored by:	AVEO Pharmaceuticals, Inc.
Information provided by:	AVEO Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier:	NCT00502307

Purpose

This phase 2 trial is evaluating the antineoplastic activity of AV-951 in treating patients with recurrent or metastatic renal cell cancer. AV-951 is a VEGF-receptor tyrosine kinase inhibitor, and may stop the growth of tumor cells by blocking blood flow to the tumor.

Condition	Intervention	Phase
Carcinoma, Renal Cell	Drug: AV-951 and placebo	Phase II

MedlinePlus related topics: Cancer

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Randomized, Double Blind (Subject, Caregiver, Investigator), Placebo Control, Parallel Assignment, Safety/Efficacy Study
Official Title:	A Phase 2, Placebo-Controlled, Randomized, Discontinuation Trial of AV-951 in Patients With Renal Cell Carcinoma

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

Primary Outcome Measures:

To determine the safety of AV-951 with this dose schedule [ Time Frame: 28 weeks after study entry ] [ Designated as safety issue: Yes ]
To determine objective response (CR + PR) rate at 16 weeks [ Time Frame: 16 weeks after study entry ] [ Designated as safety issue: No ]
To determine the percentage of randomly assigned patients remaining progression free at 12 weeks following random assignment to AV-951 or placebo [ Time Frame: 28 weeks after study entry ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Determine the progression free-survival after random assignment (randomized sub-set only) [ Time Frame: 28 weeks from study entry ] [ Designated as safety issue: No ]
Overall progression-free survival (from start of treatment) [ Time Frame: 12 months from study entry ] [ Designated as safety issue: No ]
Characterization of pharmacokinetic and pharmacodynamic (PD) profiles of AV-951 in a subset of patients [ Time Frame: 28 weeks from study entry ] [ Designated as safety issue: No ]

Estimated Enrollment:	200
Study Start Date:	October 2007
Estimated Study Completion Date:	March 2009
Estimated Primary Completion Date:	October 2008 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
1: Experimental AV-951 administered as a solid dosage form daily for three weeks per month	Drug: AV-951 and placebo solid oral dosage form taken daily for three weeks per one month cycle
2: Placebo Comparator solid oral capsule containing excipients dosed daily for three weeks per month	Drug: AV-951 and placebo solid oral dosage form taken daily for three weeks per one month cycle

Detailed Description:

Approximately 200 patients will be enroled into the initial, 16 week, open-label period using 1.5 mg/day dosing. Patients will receive AV-951 continuously for 3 weeks followed by 1 week off study drug. Patients will undergo disease assessment at baseline and after Cycles 2 and 4 and response will be determined by RESIST criteria.

After the initial, 16 week open-label period, disease status will be assessed and compared to baseline using modified RECIST criteria:

Patients with greater than or equal to 25% tumor shrinkage will continue on their current dose of AV-951
Patients with less than 25% tumor change (growth or shrinkage) will be randomly assigned to double-blind AV-951 or matching placebo for 12 weeks
Patients with greater than or equal to 25% tumor growth will be discontinued

Eligibility

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

Criteria

Inclusion Criteria:

≥ 18 year old males or females
Patients with recurrent or metastatic renal cell carcinoma (RCC) or primary RCC that is not amendable to surgical intervention
Histologically or cytologically confirmed renal cell carcinoma
Measurable disease
No more than one prior systemic treatment (chemotherapy or immunotherapy) for RCC.
No active brain metastases
Karnofsky performance status ≥ 70%, life expectancy ≥ 3 months
No childbearing potential, or use of effective contraception during the study and for 4 weeks after the last dose of study drug
Archival paraffin embedded tumor tissue, if available.
Ability to give written informed consent

Exclusion Criteria:

Pregnant or lactating women
Primary CNS malignancies; active CNS metastases
Hematologic malignancies (includes: leukemia, 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:
- Total bilirubin > 1.5 × the ULN
- AST or ALT ≥ 2.5 × the ULN
- Serum albumin < 3.0 g/dL
- Creatinine > 1.7 × ULN (or calculated CLCR <50 mL/min/1.73 m2)
- Proteinuria > 2.5 g/24 hours or 4+ with urine dipstick
Significant cardiovascular disease, including:
- Active clinically symptomatic left ventricular failure
- Active HTN (diastolic blood pressure > 100 mmHg). Patients with a history of hypertension must have been on stable doses of anti-hypertensive drugs for ≥ 4 weeks
- Uncontrolled hypertension: Blood pressure >140/90 mmHg on more than 2 antihypertensive medications.
- Myocardial infarction within 3 months prior to administration of first study dose
Unhealed wounds (including active gastric ulcers)
Serious/active infection; infection requiring parenteral antibiotics
Inadequate recovery from prior antineoplastic therapy
Inadequate recovery from any prior surgical procedure; major surgical procedure within 4 weeks prior to study entry
Life-threatening illness or organ system dysfunction compromising safety evaluation
Psychiatric disorder, altered mental status precluding informed consent or necessary testing
Inability to comply with protocol requirements

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00502307

Contacts

Contact: Pankaj Bhargava, M.D.	617-299-5000	pbhargava@aveopharma.com
Contact: Brooke Esteves, RN	617-299-5000	besteves@aveopharma.com

Locations

India, Tamil Nadu
Christian Medical College	Recruiting
Vellore, Tamil Nadu, India, 632004
Principal Investigator: Raju T Chacko, MBBS, MD
Russian Federation
Federeal State Institution Moscow Research Oncological Institute	Recruiting
Moscow, Russian Federation, 125284
Principal Investigator: Igor G Rusakov, M.D.
Non-State Medical Institution Central Clinical Hospital #2 n.a. Semashko under OAO Russian Railways	Recruiting
Moscow, Russian Federation, 129128
Principal Investigator: Mikhail Y Biakhov, MD

Sponsors and Collaborators

AVEO Pharmaceuticals, Inc.

Investigators

Principal Investigator:

Igor G Rusakov, M.D.

Oncology and Urology Dept. Federal State Institution Moscow Research Oncological Institute

More Information

No publications provided

Responsible Party:	AVEO Pharmaceuticals ( Margaret Taleff Senior Director, Regulatroy Affairs )
Study ID Numbers:	AV-951-07-201
Study First Received:	July 16, 2007
Last Updated:	April 8, 2008
ClinicalTrials.gov Identifier:	NCT00502307 History of Changes
Health Authority:	United States: Food and Drug Administration; Russia: Ethics Committee

Keywords provided by AVEO Pharmaceuticals, Inc.:

Renal Cell Carcinoma

Study placed in the following topic categories:

Urinary Tract Neoplasm
Kidney Cancer
Renal Cancer
Urologic Diseases
Kidney Neoplasms
Carcinoma, Renal Cell

Urogenital Neoplasms
Kidney Diseases
Urologic Neoplasms
Adenocarcinoma
Neoplasms, Glandular and Epithelial
Carcinoma

Additional relevant MeSH terms:

Neoplasms
Neoplasms by Site
Neoplasms by Histologic Type
Urologic Diseases
Kidney Neoplasms
Carcinoma, Renal Cell

Urogenital Neoplasms
Kidney Diseases
Urologic Neoplasms
Adenocarcinoma
Neoplasms, Glandular and Epithelial
Carcinoma

ClinicalTrials.gov processed this record on May 07, 2009