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Sorafenib Tosylate and Bevacizumab in Treating Patients With Advanced Kidney Cancer

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00126503
First received: August 2, 2005
Last updated: January 6, 2015
Last verified: September 2014
  Purpose

This phase I/II trial studies the side effects and best dose of sorafenib tosylate and bevacizumab and to see how well they work in treating patients with advanced kidney cancer. Sorafenib tosylate may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Monoclonal antibodies, such as bevacizumab, can block tumor growth by targeting certain cells. Bevacizumab and sorafenib tosylate may also stop the growth of tumor cells by blocking blood flow to the tumor. Giving sorafenib tosylate together with bevacizumab may kill more tumor cells.


Condition Intervention Phase
Chromophobe Renal Cell Carcinoma
Clear Cell Renal Cell Carcinoma
Papillary Renal Cell Carcinoma
Recurrent Renal Cell Carcinoma
Sarcomatoid Renal Cell Carcinoma
Stage IV Renal Cell Cancer
Biological: Bevacizumab
Drug: Sorafenib Tosylate
Other: Pharmacological Study
Other: Laboratory Biomarker Analysis
Phase 1
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase I/II Trial of BAY 43-9006 in Combination With Bevacizumab in Patients With Advanced Renal Cancer

Resource links provided by NLM:


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

Primary Outcome Measures:
  • Maximum Tolerated Dose (MTD) of BAY 43-9006 (Sorafenib)in Combination With Bevacizumab (Phase I) [ Time Frame: at 28 days ] [ Designated as safety issue: Yes ]
    The highest dose in milligrams (mg) of BAY 43-9006 (Sorafenib) in combination with Bevacizumab while maintaining tolerability. Cohorts of 3-6 patients received escalating doses of sorafenib and bevacizumab until the maximum tolerated dose (MTD) was achieved. The MTD is defined as the dose preceding that at which 2 or more of 6 patients experience dose-limiting toxicity during the initial cycle of therapy. DLTs include absolute neutrophil count (ANC) < 500/mm3 for > 7 days, ANC < 1000/mm3 with fever > 101 degrees Fahrenheit, platelet count < 50,000 mm3, and non-hematologic toxicity Common Toxicity Criteria (CTC) >= Grade 3.

  • Maximum Tolerated Dose of Bevacizumab in Combination With BAY 43-9006 (Sorafenib)(Phase I) [ Time Frame: at 28 days ] [ Designated as safety issue: Yes ]
    The highest dose in milligrams (mg) of Bevacizumab in combination with BAY 43-9006 (Sorafenib) while maintaining tolerability. Cohorts of 3-6 patients received escalating doses of sorafenib and bevacizumab until the maximum tolerated dose (MTD) was achieved. The MTD is defined as the dose preceding that at which 2 or more of 6 patients experience dose-limiting toxicity during the initial cycle of therapy. DLTs include absolute neutrophil count (ANC) < 500/mm3 for > 7 days, ANC < 1000/mm3 with fever > 101 degrees Fahrenheit, platelet count < 50,000 mm3, and non-hematologic toxicity Common Toxicity Criteria (CTC) >= Grade 3.

  • Objective Response [ Time Frame: Every 8 weeks to date of progression ] [ Designated as safety issue: No ]
    Objective response as determined by RECIST v. 1.0 (measurable lesions: complete response (CR) disappearance of target lesions, partial response (PR) > 30% decrease in the sum of the longest diameter (LD) of target lesions, progressive disease (PD) > 20% increase in the sum of the LD of target lesions or appearance of new lesions, stable disease (SD) neither sufficient decrease nor increase of the sum of smallest sum of the LD of target lesions)or last date known alive


Secondary Outcome Measures:
  • Overall Survival [ Time Frame: on-study to date of expired or last date known alive ] [ Designated as safety issue: No ]
    Months from date on-study to expired or last date known alive

  • Progression-free Survival [ Time Frame: on-study to date of progression or last date known alive without progression ] [ Designated as safety issue: No ]
    Duration of months of progression-free survival (PFS). Determined by months to progressive disease or to last date known alive without progressive disease.


Enrollment: 73
Study Start Date: May 2005
Study Completion Date: February 2012
Primary Completion Date: October 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment (bevacizumab and sorafenib tosylate)

Phase I: Patients receive sorafenib PO twice daily on days 1-28 and bevacizumab IV over 30-90 minutes on days 1 and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of sorafenib and bevacizumab until the MTD is determined. The MTD is defined as the dose preceding that at which 2 of 6 patients experience dose-limiting toxicity. An additional 6 patients are treated at the MTD.

Phase II: Patients receive sorafenib PO once daily on days 1-28 and bevacizumab IV over 90 minutes on days 1 and 15 at the MTD in the absence of disease progression or unacceptable toxicity.

Biological: Bevacizumab
Given IV
Other Names:
  • Avastin
  • rhuMab-VEGF
Drug: Sorafenib Tosylate
Given PO
Other Names:
  • BAY 54-9085
  • Nexavar
  • SFN
Other: Pharmacological Study
Correlative studies
Other Name: pharmacological studies
Other: Laboratory Biomarker Analysis
Correlative studies

  Show Detailed Description

  Eligibility

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

Inclusion Criteria:

  • PHASE I ELIGIBILITY CRITERIA
  • Patients must have histological or cytological confirmation of renal cell carcinoma (clear cell, papillary, chromophobe, or sarcomatoid) not curable by standard approaches; tumor must be measurable by Response Evaluation Criteria In Solid Tumors (RECIST) criteria; nephrectomy prior to enrollment is not required
  • Patients may not have had prior therapy with inhibitors of the mitogen-activated protein (MAP) kinase pathway or inhibitors of VEGF and/or its receptor signaling (VEGFR2)
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
  • Life expectancy of greater than 3 months
  • Hemoglobin (Hgb) >= 9.0gm/dl (transfusions allowed prior to enrollment)
  • White Blood Count >= 3,000/mm^3
  • Absolute Granulocyte Count >= 1,200/mm^3
  • Platelet Count >= 100,000/mm^3
  • Serum creatinine =< 1.5 x upper limit of normal (ULN) or serum creatinine clearance (CrCl) >= 40ml/min (neither drug is cleared by the kidney)
  • Total Bilirubin =< 1.5 x ULN
  • Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) =< 2.5 x ULN
  • International normalized ratio (INR) =< 1.5 and activated partial thromboplastin time (aPTT) that is not greater than 1.3 times the ULN
  • Urine Dipstick must show less then 1+ protein in urine or the patient will require 24 hour urine collection with total protein =< 1000 mg/24 hour
  • Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation; should a woman become pregnant while participating in this study, she should inform her treating physician immediately
  • Ability to understand and the willingness to sign a written informed consent document
  • PHASE II ELIGIBILITY CRITERIA
  • Patients enrolled on the phase II portion of the study will be required to have predominantly clear cell variant of renal cell carcinoma with less than 25% of any other histology (papillary or chromophobe or oncocytic); there must be histologic confirmation by treating center of either primary or metastatic lesion; patients must be willing to consent for obtaining tumor tissue blocks or unstained slides from prior biopsy or surgery; patients who participated in the Phase I part of the protocol will not be part of the accrual to the Phase II cohort
  • Patients enrolled on the phase II portion of the study will be required to have measurable disseminated disease that is not curable by standard radiation therapy or surgery
  • Previous nephrectomy is required with the following exceptions:

    • Primary tumor =< 5cm or
    • Extensive liver (> 30% of liver parenchymal) or multiple (> 5) bone metastases, or extensive extrarenal tumor or unresectable local/regional tumor extension making nephrectomy a clinically questionable and unreasonable procedure
  • For the phase II study, patients will be allowed no more than one prior regimen containing a vaccine or cytokine based immunotherapy or chemotherapy for advanced disease
  • Hgb >= 9.0gm/dl (transfusions allowed prior to enrollment)
  • White Blood Count >= 3,000/mm^3 (phase II)
  • Absolute Granulocyte Count >= 1,200/mm^3 (phase II)
  • Platelet Count >= 100,000/mm^3 (phase II)
  • Serum creatinine =< 1.5 x upper limit of normal (ULN) or serum creatinine clearance (CrCl) >= 40ml/min (neither drug is cleared by the kidney) (phase II)
  • Total Bilirubin =< 1.5 x ULN (phase II)
  • AST/ALT =< 2.5 x ULN
  • INR =< 1.5
  • Urine Dipstick must show less then 1+ protein in urine or the patient will require 24 hour urine collection with total protein =< 1000 mg/24 hour (phase II)
  • No prior malignancy diagnosed within the past 3 years with the exception of non-melanoma skin cancers, melanoma in situ, carcinoma in situ of the cervix, ductal carcinoma in situ, and lobular carcinoma in situ; any prior malignancy must have a very likely cure rate (75% or greater)
  • Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation; should a woman become pregnant while participating in this study, she should inform her treating physician immediately (phase II)
  • Ability to understand and the willingness to sign a written informed consent document (phase II)

Exclusion Criteria:

  • History or clinical evidence of central nervous system (CNS) disease, including primary brain tumor (participants with a history of meningioma are not excluded), seizures not controlled with standard medical therapy, any brain metastasis, or history of stroke within the prior 12 months; patients who have had a history of brain metastasis that have been resected or have had radiosurgery with no progression for more than 6 months are eligible if the Principle Investigator from the coordinating center is consulted and agrees
  • Patients entered onto the phase II study may not have received more than one chemotherapy or immunotherapy regimen for Stage IV disease
  • Patients may not have received chemotherapy or immunotherapy within 4 weeks of initiating treatment; patients will not have received a regimen containing a monoclonal antibody within 8 weeks of initiating treatment; toxicities from radiation must have resolved and a minimum of two weeks must pass prior to enrollment
  • Patients may not have had prior anti-angiogenic therapy including, Sunitinib, VEGF Trap; prior Temsirilomus, Everolimus, Bevacizumab and Sorafenib will not be allowed; thalidomide or interferon (IFN) alpha are allowed either for adjuvant therapy or stage IV disease
  • 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
  • History of bleeding diathesis or coagulopathy
  • A condition that impairs patient's ability to swallow pills will make patient ineligible
  • No major surgical procedure, open biopsy or significant traumatic injury within 28 days prior to initiation of therapy on trial
  • Anticipation of the need for major surgery during the course of the study
  • Current or recent use (within 7 days of starting the study drugs) of full-dose of anticoagulants (except as required to maintain patency of preexisting, permanent indwelling IV catheters or for deep vein thrombosis [DVT] prophylaxis, for subjects receiving warfarin, INR should be =< 1.5) or thrombolytic agent
  • Patients with uncontrolled hypertension; blood pressure must be =< 150/90 mmHg at the time of enrollment on a stable antihypertensive regimen
  • Patients with clinically significant cardiovascular disease within 1 year prior to study entry

    • Uncontrolled hypertension
    • Myocardial infarction or unstable angina < 6 months prior to registration
    • New York heart association grade II or greater congestive heart failure, serious cardiac arrhythmia requiring medication (participants with controlled atrial arrhythmias are not excluded), unstable angina pectoris
    • Grade II or greater peripheral vascular disease
  • Serious, non-healing wound, ulcer, or bone fracture
  • Significant proteinuria (> 1000 mg protein/24 hours ) at baseline; subjects discovered to have >= 1+ proteinuria on dipstick should undergo a 24-hour urine collection, which should contain < 1000 mg protein/ 24 hours to be allowed participation in the study
  • Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection requiring parental antibiotics, or psychiatric illness/social situations that would limit compliance with study requirements
  • Patients taking cytochrome P450 enzyme-inducing antiepileptic drugs will be excluded (phenytoin, carbamazepine, Phenobarbital, rifampin, and St.John's Wort)
  • Pregnant and lactating women are excluded from the study; breastfeeding should be discontinued while receiving therapy
  • Human immunodeficiency virus (HIV)-positive patients receiving combination anti-retroviral therapy are excluded from the study
  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: NCT00126503

Locations
United States, Massachusetts
Beth Israel Deaconess Medical Center
Boston, Massachusetts, United States, 02215
Dana-Farber Cancer Institute
Boston, Massachusetts, United States, 02115
Dana-Farber Harvard Cancer Center
Boston, Massachusetts, United States, 02115
United States, Pennsylvania
University of Pennsylvania/Abramson Cancer Center
Philadelphia, Pennsylvania, United States, 19104
United States, Tennessee
Vanderbilt-Ingram Cancer Center
Nashville, Tennessee, United States, 37232
Sponsors and Collaborators
Investigators
Principal Investigator: Jeffrey Sosman Vanderbilt-Ingram Cancer Center
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00126503     History of Changes
Other Study ID Numbers: NCI-2009-00066, NCI-2009-00066, CDR0000434814, URO 470, 6555, U01CA099177, P30CA068485
Study First Received: August 2, 2005
Results First Received: November 16, 2012
Last Updated: January 6, 2015
Health Authority: United States: Food and Drug Administration

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
Niacinamide
Sorafenib
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Antineoplastic Agents
Enzyme Inhibitors
Growth Inhibitors
Growth Substances
Micronutrients
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Protein Kinase Inhibitors
Therapeutic Uses
Vitamin B Complex
Vitamins

ClinicalTrials.gov processed this record on March 02, 2015