Lauren Harshman
A Phase 1 Study of an Oral VEGFR Inhibitor (AV-951) in Combination With Torisel in Renal Cell Cancer
Contact Information
Stanford University School of Medicine 300 Pasteur Drive Stanford, CA 94305Brief
The purpose of this study is to test the safety and tolerability of AV-951 and Torisel^TM given in combination for renal cell cancer. The study will also assess the effects of the combination of AV-951 and Torisel^TM on the tumor. 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.
Recruiting Status:
RecruitingStanford Recruiting Status:
RecruitingCondition(s):
Intervention(s):
- Drug: AV-951 plus temsirolimus
Phase:
Phase 1Eligibility
Ages Eligible for Study:
18 years to Any AgeGenders Eligible for Study:
MaleHealth of Volunteers:
People with the conditions listed in this trial can participate as controls.Key Inclusion Criteria:
- >= 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
Key Exclusion Criteria:
- 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:
o Hemoglobin < 9.0 g/dL
o ANC < 1500 per mm^3
o Platelet count < 100,000 per mm^3
- Any of the following serum chemistry abnormalities:
o Fasting serum cholesterol > 350 mg/dL
o Fasting triglycerides > 400 mg/dL
o Total bilirubin > 1.5 X ULN
o AST or ALT > 2.5 X ULN (or > 5 x ULN in subjects with liver metastasis)
o Serum albumin < 3.0 g/dL
o Creatine > 1.5 X ULN (or calculated CLCR <50 mL/min/1.73 m^2)
o Proteinuria > 2.5 g/24 hours or 3+ with urine dipstick
- Significant cardiovascular disease, including:
o Active clinically symptomatic left ventricular failure
o Active hypertension (diastolic blood pressure > 100 mmHg). Subjects with a history of hypertension must have been on stable doses of anti-hypertensive drugs for >= 4 weeks
o Uncontrolled hypertension: Blood pressure >140/90 mmHg on 2 or more antihypertensive medications
o Myocardial infarction within 3 months prior to administration of first dose of study drug
- Subjects with delayed healing of wounds, ulcers, and/or bone fractures
- Pulmonary hypertension or pneumonitis
- Serious/active infection; infection requiring parenteral antibiotics
- Inadequate recovery from any prior surgical procedure; major surgical procedure within 6 weeks prior to study entry
- Uncontrolled psychiatric disorder, altered mental status precluding informed consent or necessary testing
- Inability to comply with protocol requirements
- Ongoing hemoptysis or history of clinically significant bleeding
- Cerebrovascular accident within 12 months of study entry, or peripheral vascular disease with claudication on walking less than 1 block
- Deep venous thrombosis or pulmonary embolus within 6 months of study entry and/or ongoing need for full-dose oral or parenteral anticoagulation
- Subjects with a "currently active" second primary malignancy other than non-melanoma skin cancers. Subjects are not considered to have a "currently active" malignancy if they have completed anti-cancer therapy and are considered by their physician to be < 30% risk of relapse.
- Pregnant or lactating women
- Known concomitant genetic or acquired immune suppression disease such as HIV
Prohibited medications:
- VEGF receptor (VEGFR) targeted therapy within 4 weeks prior to and during study
- Other signal transduction inhibitors, monoclonal antibodies, etc., within 4 weeks prior to and during study
- Immunotherapy or biological response modifiers within 4 weeks prior to and during study
- Systemic hormonal therapy within 4 weeks prior to and during study, with the exception of:
o Hormonal therapy for appetite stimulation or contraception
o Nasal, ophthalmic, and topical glucocorticoid preparations
o Oral replacement therapy for adrenal insufficiency
o Low-dose maintenance steroid therapy for other conditions
- Herbal preparations/supplements (except for a daily multivitamin/mineral supplement not containing herbal components) within 2 weeks prior to or during study
- Any experimental therapy 4 weeks prior to and during study
- Radiotherapy:
o At least 2 weeks since prior local radiation therapy (ie, involving <25% of bone marrow) at the time of study entry
o At least 4 weeks since prior radiation therapy involving >= 25% of bone marrow
- Treatment with CYP3A4 inducers or inhibitors during the study
Additional Study Details
Official Title:
A Phase 1b, Open-Label, Dose-Finding Study to Evaluate the Safety of AV-951 in Combination With Temsirolimus in Subjects With Metastatic Renal Cell CarcinomaAnticipated start date:
9/10/2008Lead Sponsor:
Aveo Pharmaceuticals, Inc.Investigator(s):
Study Type:
InterventionalPurpose:
TreatmentAllocation:
Non-randomizedMasking:
OpenControl:
noneAssignment:
Single GroupEndpoints:
SafetyPrimary Outcomes:
- To determine the safety and tolerability of AV-951 when given in combination with temsirolimus
Secondary Outcomes:
- To characterize the pharmacokinetic profile of AV-951 and temsirolimus when administered in combination
- To evaluate the antineoplastic activity of AV-951 and temsirolimus when administered in combination
- To evaluate the effect of AV-951 and temsirolimus on global and targeted gene expression patterns
- To determine the maximum tolerated dose (MTD) of AV-951 when administered in combination with temsirolimus
Total Number to be Enrolled:
35Total Number to be Enrolled at Stanford:
10More Information
Secondary ID(s):
- AV-951-07-102
- AV-951-102
- NCT00563147
- RENAL0017
Locations & Contacts
Stanford Locations & Contacts:
Stanford University School of Medicine 300 Pasteur Drive Stanford, CA 94305Non-Stanford Locations:
The Stanford website does not have any locations outside of Stanford listed for this trial. You may want to check clinicaltrials.gov for posible additional locations.
This listing was last updated:
9/9/2009PLEASE NOTE:
Study Coordinators and Research Nurses cannot give medical advice over the phone. Telephone numbers are provided for obtaining additional information on specific clinical research trials only. If you have specific questions which require clinical expertise, please call your primary care physician. If you do not have a primary care physician please feel free to call the SHC Physician Referral Service at (800) 756-9000 or send an email.
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