Bevacizumab and BKM-120 in Patients With Metastatic Renal Cell Carcinoma

Study Overview
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Brief Summary
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BKM-120 is a drug that may slow the growth of cancer cells. This drug has been used in laboratory experiments and information from those research studies suggests that this drug may help to slow the growth of renal cancer cells. In this research study, the investigators are testing the safety to BKM-120 at different dose levels. The investigators will also be studying how well tolerated BKM-120 is, and how effective BKM-120 can be in the treatment of kidney cancer.

Detailed Description
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Subjects will receive an intravenous infusion of Avastin on Day 1 and Day 15 of each month (cycle). Subjects will take a daily oral dose of BKM-120 at the dose level assigned. Subjects will have a clinic visit weekly during Cycle 1 and then on Day 1 and Day 15 of each cycle for blood tests and physical exam.

Official Title
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A Phase I Study of Bevacizumab and Escalation Doses of BKM-120 in Patients With Metastatic Renal Cell Carcinoma Who Failed Prior Systemic Therapies

Conditions
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Renal Cell Carcinoma

Intervention / Treatment
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* Drug: BKM-120 Bevacizumab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Metastatic RCC with clear cell component or papillary RCC Life expectancy > 12 weeks Must have failed at least 1 prior anti-VEGF systemic therapy for metastatic RCC Exclusion Criteria: Prior treatment with a P13K inhibitor or bevacizumab Untreated brain metastases Acute or chronic liver or pancreatic disease Major mood disorder Concurrent severe and/or uncontrolled medical condition Diabetes mellitus GI disease Currently taking therapeutic doses of warfarin sodium or any other coumadin-derivative anticoagulant Pregnant or breastfeeding HIV positive History of another malignancy within 3 years except cured basal cell carcinoma of the skin or excised in situ carcinoma of the cervix Uncontrolled hypertension

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: BKM-120 Bevacizumab<br>BKM-120 60, 80, 100 mg PO QD Bevacizumab 10 mg/Kg every 2 weeks | Drug: BKM-120 Bevacizumab<br>* BKM-120 60, 80, 100 mg PO QD Bevacizumab 10 mg/Kg every 2 weeks<br>* Other names: Avastin;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To determine the maximum tolerated dose and dose limiting toxicities of the combination of BKM-120 and bevacizumab in metastatic renal cell carcinoma |  | 2 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To determine additional toxicity and safety information from the combination of BKM-120 and bevacizumab in an expanded cohort of patients at the MTD |  | 2 year | 
| To determine the objective response proportion, progression-free survival, overall survival of the combination of BKM-120 and bevacizumab |  | 2 years | 
| To determine whether the BKM-120 and bevacizumab combination at the MTD is associated with concomitant changes in angiokines and PI3K pathway members in plasma and tumor samples |  | 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Kidney Cancer, Avastin