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Bevacizumab With or Without Sunitinib in Sunitinib-Refractory Renal Cell Carcinoma

This study has been withdrawn prior to enrollment.
(Toxicity of combination from other trials)
Sponsor:
Collaborators:
Beth Israel Deaconess Medical Center
Pfizer
Information provided by:
Massachusetts General Hospital
ClinicalTrials.gov Identifier:
NCT00556205
First received: November 7, 2007
Last updated: July 19, 2011
Last verified: July 2011
  Purpose

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.


Condition Intervention Phase
Renal Cell Carcinoma
Drug: Sunitinib
Drug: Bevacizumab
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Crossover Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase II, Randomized Trial of Bevacizumab With or Without Sunitinib in Sunitinib-Refractory Patients With Metastatic Renal Cell Carcinoma

Resource links provided by NLM:


Further study details as provided by Massachusetts General Hospital:

Primary Outcome Measures:
  • To determine the time to tumor progression (TTP) in this patient population treated with bevacizumab or combination of sunitinib and bevacizumab. [ Time Frame: Until tumor progression ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • To determine the overall response rate in this patient population. [ Time Frame: Until tumor progression ] [ Designated as safety issue: No ]
  • To evaluate the safety and tolerability of these treatments in mRCC patients with disease progression on standard dose sunitinib. [ Time Frame: Until tumor progression ] [ Designated as safety issue: Yes ]
  • To collect serum research samples for analysis of predictive biomarkers of response. [ Time Frame: Two months ] [ Designated as safety issue: No ]

Estimated Enrollment: 54
Study Start Date: September 2009
Study Completion Date: September 2009
Primary Completion Date: September 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: 1
Bevacizumab monotherapy
Drug: Bevacizumab
Intravenously every 14 days
Other Name: avastin
Active Comparator: 2
Combination Sunitinib & Bevacizumab
Drug: Sunitinib
Sunitinib orally once daily
Other Name: sutent
Drug: Bevacizumab
Intravenously every 14 days
Other Name: avastin

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

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00556205

Sponsors and Collaborators
Massachusetts General Hospital
Beth Israel Deaconess Medical Center
Pfizer
Investigators
Principal Investigator: M. Dror Michaelson, MD, PhD Massachusetts General Hosptial
  More Information

No publications provided

Responsible Party: M. Dror Michaelson MD PhD, Massachusetts General Hospital
ClinicalTrials.gov Identifier: NCT00556205     History of Changes
Other Study ID Numbers: 07-202
Study First Received: November 7, 2007
Last Updated: July 19, 2011
Health Authority: United States: Institutional Review Board

Keywords provided by Massachusetts General Hospital:
mRCC
sunitinib
bevacizumab

Additional relevant MeSH terms:
Carcinoma
Carcinoma, Renal Cell
Adenocarcinoma
Kidney Diseases
Kidney Neoplasms
Neoplasms
Neoplasms by Histologic Type
Neoplasms by Site
Neoplasms, Glandular and Epithelial
Urogenital Neoplasms
Urologic Diseases
Urologic Neoplasms
Bevacizumab
Sunitinib
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Antineoplastic Agents
Growth Inhibitors
Growth Substances
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses

ClinicalTrials.gov processed this record on November 20, 2014