Clinical trial NCT00556205: Bevacizumab With or Without Sunitinib in Sunitinib-Refractory Renal Cell Carcinoma
Official title: Phase II, Randomized Trial of Bevacizumab With or Without Sunitinib in Sunitinib-Refractory Patients With Metastatic Renal Cell Carcinoma
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE2
Conditions: Renal Cell Carcinoma
Keywords: mRCC
sunitinib
bevacizumab
Lead sponsor: Massachusetts General Hospital
Sponsor class: OTHER
Collaborators: name: Beth Israel Deaconess Medical Center
name: Pfizer
First posted: 2007-11-09
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: The purpose of this research study is to further define an effective strategy for people with renal cell carcinoma and to learn the safety and effectiveness of two different types of sunitinib-refractory treatments: Bevacizumab alone or a combination of sunitinib and bevacizumab. Sunitinib is an FDA approved drug and is currently one of the standard treatments for advanced renal cell carcinoma. However, some people who receive this treatment do not respond to treatment or they stop responding to treatment. Bevacizumab is an FDA approved drug used for the treatment of several cancers however, is not yet approved for use in renal cell carcinoma.

Detailed description: * Participants will receive one of two treatment possibilities. Since no one knows which of the study options is best, participants will be "randomized" to one fo the three treatment groups.
* Group 1 will stop their current treatment with sunitinib and receive a dose of bevacizumab once every 2 weeks. Group 2 will receive the standard treatment of sunitinib with the addition of bevacizumab.
* All study participants will undergo the same study procedures. These study procedures will include the following at intervals specified in the protocol: medical history review; vital signs; physical exam; urine analysis; EKG and CT scan.

Eligibility criteria: Inclusion Criteria:

* Histologically confirmed metastatic renal cell carcinoma with clear cell histology
* Patients must be off sunitinib for 14 days prior to day 1 of treatment on protocol
* Evidence of unidimensionally measurable disease based on RECIST criteria, with at least 1 measurable lesion
* Radiographic evidence of disease progression defined by RECIST during or within 6 weeks of completion of sunitinib treatment
* Participants must have received at least 14 doses of sunitinib therapy
* Participants must enroll within 3 months of the last dose of sunitinib
* Males or females, age of 18 years or older
* ECOG Performance status 0-2
* Resolution of all acute toxic effects of prior therapy, radiotherapy or surgical procedures to NCI CTCAE version 3.0 grade 1 or less
* Laboratory values as defined in protocol
* 4 weeks or more must have elapsed from the time of major surgery and subjects must have recovered from the procedure prior to day 1 of randomization
* No anticipated need for major surgical procedure during the course of the study
* 2 weeks or more must have elapsed from the time of minor surgery and subjects must have recovered from the procedure prior to day 1 of randomization
* 4 weeks of more must have elapsed from the time of major radiotherapy prior to day 1 of randomization

Exclusion Criteria:

* Prior treatment with bevacizumab
* Unacceptable toxicity on prior sunitinib therapy at 37.5mg or lower
* Prior systemic therapy for RCC with \> 2 regimens
* Systemic therapy other than sunitinib within 4 weeks of starting the study treatment
* Uncontrolled high blood pressure
* Any prior history of hypertensive crisis or hypertensive encephalopathy
* History of abdominal fistula, gastrointestinal perforation or intraabdominal abscess within 3 months prior to day 0
* Any of the following within the 6 months prior to sudy drug administration: myocardial infarction, severe/unstable angina, coronary/peripheral artery bypass graft, cerebrovascular accident or transient ischemic attack, symptomatic congestive heart failure, or ejection fraction \< 30%
* Pre-existing thyroid abnormality with thyroid function that cannot be maintained in the normal range without medication
* History of or known brain metastases or spinal cord compression
* NCI CTCAE grade 2 or above hemorrhage within 4 weeks of starting study treatment
* Significant vascular disease (e.g., aortic aneurysm, aortic dissection)
* Symptomatic peripheral vascular disease
* Grade 3 or higher cardiac dysrhythmia or QT prolongation
* Concurrent use of proarrhythmic medications including terfenadine, quinidine, procainamide, disopyramide, sotalol, probucol, bepridil, haloperidol, risperidone, indapamide and flecainide
* Pregnancy or breastfeeding or inadequate contraception
* Significant thromboembolic event within 6 months
* Evidence of bleeding diathesis or coagulopathy
* Serious, non-healing wound, ulcer or bone fracture
* Proteinuria at screening
* Known hypersensitivity to any component of bevacizumab
* Psychiatric illness/social situation that would limit compliance with study requirements
* Previous or concurrent malignancy requiring active systemic therapy

Primary outcomes:
measure: To determine the time to tumor progression (TTP) in this patient population treated with bevacizumab or combination of sunitinib and bevacizumab.
timeFrame: Until tumor progression
Secondary outcomes:
measure: To determine the overall response rate in this patient population.
timeFrame: Until tumor progression
measure: To evaluate the safety and tolerability of these treatments in mRCC patients with disease progression on standard dose sunitinib.
timeFrame: Until tumor progression
measure: To collect serum research samples for analysis of predictive biomarkers of response.
timeFrame: Two months
Other outcomes:
Locations:
Study officials:
affiliation: Massachusetts General Hosptial
name: M. Dror Michaelson, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: