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Bevacizumab, Sorafenib, and Temsirolimus in Treating Patients With Metastatic Kidney Cancer
This study is currently recruiting participants.
Verified by National Cancer Institute (NCI), May 2009
First Received: September 19, 2006   Last Updated: May 7, 2009   History of Changes
Sponsors and Collaborators: Eastern Cooperative Oncology Group
National Cancer Institute (NCI)
Information provided by: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00378703
  Purpose

RATIONALE: Monoclonal antibodies, such as bevacizumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Bevacizumab and sorafenib may stop the growth of tumor cells by blocking blood flow to the tumor. Temsirolimus and sorafenib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving different combinations of bevacizumab, sorfenib, and temsirolimus may be more effective than bevacizumab alone in treating metastatic kidney cancer.

PURPOSE: This randomized phase II trial is studying different combinations of bevacizumab, temsirolimus, and sorafenib to see how well they work compared with bevacizumab alone in treating patients with metastatic kidney cancer.


Condition Intervention Phase
Kidney Cancer
Biological: bevacizumab
Drug: sorafenib tosylate
Drug: temsirolimus
Phase II

MedlinePlus related topics: Cancer Kidney Cancer
Drug Information available for: CCI 779 Bevacizumab Sorafenib Sorafenib tosylate
U.S. FDA Resources
Study Type: Interventional
Study Design: Treatment, Randomized
Official Title: The BeST Trial: A Randomized Phase II Study of VEGF, RAF Kinase, and mTOR Combination Targeted Therapy (CTT) With Bevacizumab, Sorafenib and Temsirolimus in Advanced Renal Cell Carcinoma [BeST]

Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Progression-free survival [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Safety [ Designated as safety issue: Yes ]
  • Overall survival as assessed by the Kaplan-Meier method [ Designated as safety issue: No ]
  • Objective response rate [ Designated as safety issue: No ]
  • Number and percentage of patients with stable disease at 6 months [ Designated as safety issue: No ]

Estimated Enrollment: 360
Study Start Date: September 2007
Estimated Primary Completion Date: May 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Arm A: Active Comparator
Patients receive bevacizumab IV over 30-90 minutes on days 1 and 15.
Biological: bevacizumab
Given IV
Arm B: Experimental
Patients receive temsirolimus IV over 30 minutes on days 1, 8, 15, and 22 and bevacizumab as in arm A.
Biological: bevacizumab
Given IV
Drug: temsirolimus
Given IV
Arm C: Experimental
Patients receive bevacizumab as in arm A and oral sorafenib tosylate twice daily on days 1-28.
Biological: bevacizumab
Given IV
Drug: sorafenib tosylate
Given orally
Arm D: Experimental
Patients receive temsirolimus as in arm B and sorafenib tosylate as in arm C.
Drug: sorafenib tosylate
Given orally
Drug: temsirolimus
Given IV

Detailed Description:

OBJECTIVES:

Primary

  • Compare progression-free survival (PFS) of patients with advanced renal cell carcinoma treated with different combinations of bevacizumab, sorafenib tosylate, and temsirolimus vs bevacizumab alone.

Secondary

  • Assess the significance of changes in tumor size over early time points as a predictor of PFS of patients treated with these regimens.
  • Compare the number and percentage of patients with stable disease at 6 months of therapy (failure to progress).
  • Compare the safety of these regimens in these patients.
  • Compare overall survival of patients treated with these regimens.
  • Compare the objective response rate in patients treated with these regimens.
  • Assess pathology, angiogenesis histology, and activation status of MAP kinase and VEGFR2 pathways and relate to clinical outcome.

OUTLINE: This is a randomized, multicenter study. Patients are stratified according to prior cytokine or vaccine therapy (no vs yes) and Motzer risk category (low vs intermediate vs high). Patients are randomized to 1 of 4 treatment arms.

  • Arm A: Patients receive bevacizumab IV over 30-90 minutes on days 1 and 15.
  • Arm B: Patients receive temsirolimus IV over 30 minutes on days 1, 8, 15, and 22 and bevacizumab as in arm A.
  • Arm C: Patients receive bevacizumab as in arm A and oral sorafenib tosylate twice daily on days 1-28.
  • Arm D: Patients receive temsirolimus as in arm B and sorafenib tosylate as in arm C.

In all arms treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed periodically for 5 years.

PROJECTED ACCRUAL: A total of 360 patients will be accrued for this study.

  Eligibility

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

DISEASE CHARACTERISTICS:

  • Histologically confirmed clear cell renal cell carcinoma

    • Primary or metastatic lesion
    • Less than 25% of any other histology (papillary, chromophobe, or oncocytic)
  • Sufficient pathology material available for diagnostic review

    • Core-needle biopsy allowed
    • No fine-needle aspirations as only source for diagnosis
  • Measurable metastatic disease
  • Not curable by standard radiotherapy or surgery
  • Prior nephrectomy required, with the following exceptions:

    • Primary tumor ≤ 5 cm
    • Extensive liver metastases (> 30% of liver parenchymal) or multiple (> 5) bone metastases
  • No history or clinical evidence of CNS disease, including primary brain tumor or brain metastases

PATIENT CHARACTERISTICS:

  • ECOG performance status 0-1
  • Life expectancy > 3 months
  • WBC ≥ 3,000/mm³
  • Absolute granulocyte count ≥ 1,200/mm³
  • Platelet count ≥ 100,000/mm³
  • Hemoglobin ≥ 9.0 g/dL (transfusions allowed)
  • Creatinine ≤ 1.5 times upper limit of normal (ULN) OR creatinine clearance ≥ 55 mL/min
  • Bilirubin ≤ 1.5 times ULN
  • AST/ALT ≤ 2.5 times ULN (5.0 times ULN in the presence of liver metastases)
  • INR ≤ 1.5 and aPTT normal
  • Fasting cholesterol < 350 mg/dL
  • Fasting triglycerides < 400 mg/dL
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception during and for 6 months after completion of study treatment
  • No seizures not controlled with standard medical therapy
  • No stroke within the past 12 months
  • No other malignancies within the past 5 years except basal cell skin cancer, squamous cell skin cancer, carcinoma in situ of the cervix, or ductal or lobular carcinoma in situ of the breast
  • No history of allergic reactions attributed to Chinese hamster ovary cell products, other recombinant human antibodies, or compounds of similar chemical or biologic composition to sorafenib tosylate, temsirolimus, or bevacizumab
  • No history of bleeding diathesis or coagulopathy
  • No condition that impairs ability to swallow pills
  • No significant traumatic injury within the past 28 days
  • No clinically significant cardiovascular disease, including any of the following:

    • Uncontrolled hypertension

      • Blood pressure must be ≤ 150/100 mm Hg on a stable antihypertensive regimen
    • Myocardial infarction or unstable angina within the past 6 months
    • New York Heart Association class II-IV congestive heart failure
    • Serious cardiac arrhythmia requiring medication
    • Unstable angina pectoris
    • Peripheral vascular disease ≥ grade 2
  • No serious, nonhealing wound, ulcer, or bone fracture
  • No significant proteinuria

    • If urine protein:creatinine ratio > 0.5, 24-hour urine protein must be < 1,000 mg
  • No uncontrolled intercurrent illness including, but not limited to, ongoing or active infection requiring parental antibiotics on day 0 or psychiatric illness or social situations that would preclude compliance with study requirements

PRIOR CONCURRENT THERAPY:

  • See Disease Characteristics
  • No more than 1 prior regimen containing vaccine- or cytokine-based immunotherapy for advanced disease
  • No prior antiangiogenic therapy including, but not limited to, sunitinib malate, ZD6474, or VEGF Trap
  • No prior bevacizumab, mTOR inhibitors (including, but not limited to, temsirolimus), or sorafenib tosylate
  • Prior thalidomide or interferon alfa allowed as adjuvant therapy or for stage IV disease
  • More than 4 weeks since prior immunotherapy
  • More than 2 weeks since prior radiotherapy and recovered
  • More than 4 weeks since prior major surgery or open biopsy
  • No concurrent major surgery
  • No concurrent or recent full-dose anticoagulants or thrombolytic agents (unless required to maintain patency of pre-existing or permanent indwelling IV catheters)
  • No concurrent cytochrome P450 enzyme-inducing drugs including any of the following:

    • Phenytoin
    • Carbamazepine
    • Phenobarbital
    • Rifampin
  • No concurrent combination antiretroviral therapy for HIV-positive patients
  • No other concurrent anticancer therapies or investigational agents
  • No concurrent prophylactic hematopoietic colony-stimulating factors
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00378703

  Show 275 Study Locations
Sponsors and Collaborators
Eastern Cooperative Oncology Group
Investigators
Study Chair: Keith T. Flaherty, MD University of Pennsylvania
Investigator: David F. McDermott, MD Beth Israel Deaconess Medical Center
  More Information

Additional Information:
No publications provided

Responsible Party: ECOG Group Chair's Office ( Robert L. Comis )
Study ID Numbers: CDR0000499788, ECOG-E2804
Study First Received: September 19, 2006
Last Updated: May 7, 2009
ClinicalTrials.gov Identifier: NCT00378703     History of Changes
Health Authority: Unspecified

Keywords provided by National Cancer Institute (NCI):
recurrent renal cell cancer
clear cell renal cell carcinoma
stage IV renal cell cancer

Study placed in the following topic categories:
Urinary Tract Neoplasm
Kidney Cancer
Urogenital Neoplasms
Bevacizumab
Urologic Neoplasms
Protein Kinase Inhibitors
Angiogenesis Inhibitors
Recurrence
Carcinoma
Renal Cancer
Urologic Diseases
Kidney Neoplasms
Carcinoma, Renal Cell
Clear Cell Renal Cell Carcinoma
Kidney Diseases
Adenocarcinoma
Sorafenib
Neoplasms, Glandular and Epithelial

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

ClinicalTrials.gov processed this record on May 07, 2009