Sorafenib Tosylate and Bevacizumab in Treating Patients With Advanced Kidney Cancer

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00126503
First received: August 2, 2005
Last updated: March 19, 2014
Last verified: March 2014
  Purpose

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 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 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. This phase I/II trial is studying 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.


Condition Intervention Phase
Clear Cell Renal Cell Carcinoma
Recurrent Renal Cell Cancer
Stage IV Renal Cell Cancer
Biological: bevacizumab
Drug: sorafenib tosylate
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
Primary Completion Date: March 2012 (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:
  • anti-VEGF humanized monoclonal antibody
  • anti-VEGF monoclonal antibody
  • Avastin
  • rhuMAb VEGF
Drug: sorafenib tosylate
Given PO
Other Names:
  • BAY 43-9006
  • BAY 43-9006 Tosylate Salt
  • BAY 54-9085
  • Nexavar
  • SFN

  Show Detailed Description

  Eligibility

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

Inclusion Criteria:

  • Histologically or cytologically confirmed renal cell carcinoma (RCC) of 1 of the following types:

    • Clear cell
    • Papillary (phase I only)
    • Chromophobe (phase I only)
    • Sarcomatoid (phase I only) [Note: Clear cell RCC with < 25% of any other histology (e.g., papillary, chromophobe, or oncocytic) required for enrollment in the phase II portion of the study]
  • Advanced disease
  • Measurable disease not curable by standard therapy (for patients in the phase I portion of the study only)
  • Measurable disseminated disease that is not curable by standard radiotherapy or surgery (for patients in the phase II portion of the study only)
  • Has undergone prior nephrectomy, unless 1 of the following is true (phase II):

    • Primary tumor =< 5 cm
    • Extensive liver metastases (i.e., > 30% of liver parenchyma) OR multiple bone metastases (i.e., > 5) OR extensive extrarenal tumor or unresectable local/regional tumor extension making nephrectomy a clinically questionable and unreasonable procedure
  • Tumor tissue block available (for patients in the phase II portion of the study only)
  • No history or clinical evidence of CNS disease, including primary brain tumor (history of meningioma allowed), or brain metastasis
  • Patients with a history of brain metastasis that have been resected or have had radiosurgery with no progression for man than 6 months are eligible
  • Performance status:

    • ECOG 0-1
  • Life expectancy:

    • More than 3 months
  • Hematopoietic:

    • Hemoglobin >= 9.0 g/dL (transfusion allowed)
    • WBC >= 3,000/mm3
    • Absolute granulocyte count >= 1,200/mm3
    • Platelet count >= 100,000/mm3
    • No history of bleeding diathesis or coagulopathy
  • Hepatic:

    • Bilirubin =< 1.5 times upper limit of normal (ULN)
    • AST and ALT =< 2.5 times ULN
    • INR =< 1.5
    • aPTT =< 1.3 times ULN
  • Renal:

    • Creatinine =< 1.5 times ULN (2.0 times ULN for patients in the phase II portion of the study) OR
    • Creatinine clearance >= 40 mL/min
    • Urine protein < 1+ by dipstick OR =< 1,000 mg by 24-hour urine collection
  • No uncontrolled hypertension
  • Blood pressure must be =< 150/90 mm Hg on a stable antihypertensive regimen
  • No myocardial infarction within the past 6 months
  • No unstable angina pectoris within the past 6 months
  • No New York Heart Association grade II-IV congestive heart failure
  • No peripheral vascular disease >= grade 2 within the past year
  • No history of stroke
  • No other clinically significant cardiovascular disease
  • Negative pregnancy test
  • Fertile patients must use effective contraception prior to, during, and for >= 3 months after completion of study treatment
  • No condition that would preclude ability to swallow pills
  • No other malignancy within the past 3 years with the exception of non-melanoma skin cancer, melanoma in situ, cervical cancer, ductal carcinoma in situ, or lobular carcinoma in situ (for patients in the phase II portion of the study only)
  • No prior malignancy that does not have a very likely cure rate (i.e., approximately 75% or greater) (for patients in the phase II portion of the study only)
  • No history of allergic reaction attributed to Chinese hamster ovary cell products, other recombinant human antibodies, or compounds of similar chemical or biological composition to sorafenib
  • No psychiatric illness or social situation that would preclude study compliance
  • No serious non-healing wound, ulcer, or bone fracture
  • No history or clinical evidence of uncontrolled seizures
  • No significant traumatic injury within the past 28 days
  • No ongoing or active infection requiring parenteral antibiotics
  • No other uncontrolled illness
  • No history of seizures unless controlled with standard medical therapy
  • More than 4 weeks since prior immunotherapy
  • More than 8 weeks since prior monoclonal antibodies
  • No more than 1 prior vaccine or cytokine-based immunotherapy regimen for stage IV disease (for patients in the phase II portion of the study only)
  • No prior vascular endothelial growth factor (VEGF) or VEGF signaling inhibitors
  • No prior bevacizumab or sorafenib
  • No other prior antiangiogenic therapy (e.g., SU011248, ZD6474, or VEGF Trap)
  • Prior thalidomide or interferon alfa as adjuvant therapy or for treatment of stage IV disease allowed
  • No concurrent prophylactic granulocyte or platelet colony-stimulating factors
  • More than 4 weeks since prior chemotherapy
  • No prior chemotherapy regimen for stage IV disease (for patients in the phase II portion of the study only)
  • Prior immunotherapy is not considered chemotherapy
  • At least 2 weeks since prior radiotherapy and recovered
  • More than 4 weeks since prior major surgical procedure or open biopsy
  • No concurrent major surgery
  • No prior MAP kinase pathway inhibitors (for patients in the phase II portion of the study only)
  • No prior experimental therapy for advanced RCC (for patients in the phase II portion of the study only)
  • No concurrent or recent (within 7 days of starting study drugs) use of full-dose anticoagulants or thrombolytic agents
  • Concurrent anticoagulants to maintain patency of preexisting, permanent indwelling IV catheters allowed
  • Concurrent warfarin allowed provided INR =< 1.5
  • No concurrent P450 enzyme-inducing antiepileptic drugs (e.g., phenytoin, carbamazepine, phenobarbital, rifampin, or Hypericum perforatum [St. John's wort])
  • No concurrent combination anti-retroviral therapy for HIV-positive patients
  • Not pregnant
  • No nursing during and for >= 3 months after completion of study treatment
  Contacts and Locations
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
Abramson Cancer Center of The University of Pennsylvania
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: March 19, 2014
Health Authority: United States: Food and Drug Administration

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

ClinicalTrials.gov processed this record on April 23, 2014