Clinical trial NCT00073307: Study of BAY43-9006 in Patients With Unresectable and/or Metastatic Renal Cell Cancer
Official title: A Phase III Randomized Study of BAY43-9006 in Patients With Unresectable and/or Metastatic Renal Cell Cancer.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Carcinoma, Renal Cell
Keywords: Renal Cell Cancer (RCC)
Cancer
Lead sponsor: Bayer
Sponsor class: INDUSTRY
Collaborators: name: Amgen
First posted: 2003-11-21
Enrollment: 903
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to evaluate safety, efficacy (including quality of life), and pharmacokinetics of BAY43-9006 when added to Best Supportive Care in patients with unresectable and/or metastatic renal cell cancer, who have received one prior systemic regimen for advanced disease.

Detailed description: Overall Survival (OS), Patient-reported outcome (PRO)

Eligibility criteria: Inclusion Criteria:

* Patients with unresectable and/or metastatic, measurable renal cell carcinoma histologically or cytologically documented
* Patients must have had one prior systemic therapy for advanced disease, which was completed at least 30 days but no longer than 8 months prior to randomization
* Patients who have at least one uni-dimensional measurable lesion by CT-scan or MRI according to Response Evaluation Criteria in Solid Tumors (RECIST)
* Patients who have an Eastern Co-operative Oncology Group (ECOG) performance status of 0 or 1
* Patients who have adequate coagulation, liver and kidney functions

Exclusion Criteria:

* Patients with rare subtypes of renal cell carcinoma (RCC) such as pure papillary cell tumors, mixed tumor containing predominantly sarcomatoid cells, Bellini carcinoma, medullary carcinoma, or chromophobe oncocytic tumors
* Previous malignancy (except for cervical carcinoma in situ, adequately treated basal cell carcinoma,or superficial bladder tumors, or other malignancies curatively treated \> 2 years prior to entry
* Cardiac arrhythmias requiring anti-arrhythmics, symptomatic coronary artery disease or ischemia or congestive heart failure
* Patients with a history of human immunodeficiency virus (HIV) infection or chronic hepatitis B or C
* Patients with a history or presence of metastatic brain or meningeal tumors
* Patients with seizure disorder requiring medication (such as anti-epileptics)
* History of organ allograft or bone marrow transplant of stem cell rescue
* Patients who are pregnant or breast-feeding Women of childbearing potential must have a negative pregnancy test prior to drug administration. Both men and women enrolled in this trial must use adequate birth control
* Patients who have three or more of the following:

  * ECOG performance status greater than or equal to 2,
  * Abnormally high lactate dehydrogenase,
  * Abnormally high serum hemoglobin,
  * Abnormally high corrected serum calcium,
  * Absence of prior nephrectomy
* Excluded therapies and medications, previous and concomitant:

  * Concurrent anti-cancer chemotherapy, immunotherapy or hormonal therapy except biphosphonates
  * Significant surgery with 4 weeks of start of study
  * Investigational drug therapy during or within 30 days
  * Concomitant treatment with rifampin or St. John's Wort
  * Prior use of Raf-kinase inhibitors (RKI), MEK or Farnesyl transferase inhibitors
  * Prior use of Bevacizumab, and all other drugs (investigational or licensed) that target VEGF/VEGF receptors

Primary outcomes:
measure: Final Overall Survival (OS) - Primary Analysis in the ITT (Intent To Treat) Population
timeFrame: From start of randomization of the first subject (1Dec2003) until the data cut-off (8Sep2006) for the final OS analysis, approximately 33 months later
measure: Final Overall Survival - Secondary Analysis (Placebo Data Censored at 30June2005) in the ITT Population
timeFrame: From start of randomization of the first subject (1Dec2003) until the data cut-off (8Sep2006) for the final OS analysis, approximately 33 months later
Secondary outcomes:
measure: Final Progression-Free Survival (PFS) - Independent Radiological Review
timeFrame: From start of randomization of the first subject (1Dec2003) until the data cut-off (28Jan2005), approximately 14 months later, tumors assessed every 8 weeks.
measure: Best Overall Response - Independent Radiological Review
timeFrame: From start of randomization of the first subject (1Dec2003) until the data cut-off (28Jan2005), approximately 14 months later, tumors assessed every 8 weeks.
measure: Health-related Quality of Life (HRQOL) by FKSI-10 (Functional Assessment of General Therapy Kidney Symptom Index 10) Assessment
timeFrame: From start of randomization of the first subject (1Dec2003) until the data cut-off (31May2005), approximately 18 months later, PRO data collected at Day 1 of each cycle and end of treatment.
measure: Health-related Quality of Life (HRQOL) by Physical Well-Being (PWB) Score of the FACT-G (Functional Assessment of Cancer Therapy-General Version) Assessment
timeFrame: From start of randomization of the first subject (1Dec2003) until the data cut-off (31May2005), approximately 18 months later, PRO data collected at Day 1 of each cycle and end of treatment.
Other outcomes:
Locations:
city: Tucson
country: United States
state: Arizona
city: Los Angeles
country: United States
state: California
city: Los Angeles
country: United States
state: California
city: Sacramento
country: United States
state: California
city: Aurora
country: United States
state: Colorado
city: Hamden
country: United States
state: Connecticut
city: Atlanta
country: United States
state: Georgia
city: Chicago
country: United States
state: Illinois
city: Louisville
country: United States
state: Kentucky
city: Lafayette
country: United States
state: Louisiana
city: Frederick
country: United States
state: Maryland
city: Boston
country: United States
state: Massachusetts
city: Minneapolis
country: United States
state: Minnesota
city: Columbia
country: United States
state: Missouri
city: St. Louis
country: United States
state: Missouri
city: Bronx
country: United States
state: New York
city: Brooklyn
country: United States
state: New York
city: New York
country: United States
state: New York
city: Canton
country: United States
state: Ohio
city: Cleveland
country: United States
state: Ohio
city: Dayton
country: United States
state: Ohio
city: Portland
country: United States
state: Oregon
city: Philadelphia
country: United States
state: Pennsylvania
city: Spartanburg
country: United States
state: South Carolina
city: Dallas
country: United States
state: Texas
city: Laredo
country: United States
state: Texas
city: San Antonio
country: United States
state: Texas
city: Salt Lake City
country: United States
state: Utah
city: Richmond
country: United States
state: Virginia
city: Seattle
country: United States
state: Washington
city: Milwaukee
country: United States
state: Wisconsin
city: Rosario
country: Argentina
state: Santa Fe
city: Santa Fé
country: Argentina
state: Santa Fe
city: Capital Federal-Buenos Aires
country: Argentina
city: Mendoza
country: Argentina
city: Garran
country: Australia
state: Australian Capital Territory
city: Camperdown
country: Australia
state: New South Wales
city: Liverpool
country: Australia
state: New South Wales
city: Westmead
country: Australia
state: New South Wales
city: Heidelberg
country: Australia
state: Victoria
city: Wodonga
country: Australia
state: Victoria
city: Bruxelles - Brussel
country: Belgium
city: Bruxelles - Brussel
country: Belgium
city: Curitiba
country: Brazil
state: Parana
city: Porto Alegre
country: Brazil
state: Rio Grande do Sul
city: Porto Alegre
country: Brazil
state: Rio Grande do Sul
city: Edmonton
country: Canada
state: Alberta
city: Hamilton
country: Canada
state: Ontario
city: London
country: Canada
state: Ontario
city: Toronto
country: Canada
state: Ontario
city: Montreal
country: Canada
state: Quebec
city: Santiago de Chile
country: Chile
city: Bordeaux
country: France
city: Caen Cedex 5
country: France
city: Lille Cedex
country: France
city: Lyon Cedex
country: France
city: Marseille
country: France
city: Nantes
country: France
city: Paris Cedex 15
country: France
city: Strasbourg
country: France
city: Toulouse
country: France
city: Villejuif
country: France
city: Mannheim
country: Germany
state: Baden-Württemberg
city: Ulm
country: Germany
state: Baden-Württemberg
city: München
country: Germany
state: Bayern
city: Regensburg
country: Germany
state: Bayern
city: Darmstadt
country: Germany
state: Hessen
city: Frankfurt
country: Germany
state: Hessen
city: Düsseldorf
country: Germany
state: Nordrhein-Westfalen
city: Dresden
country: Germany
state: Sachsen
city: Berlin
country: Germany
city: Hamburg
country: Germany
city: Budapest
country: Hungary
city: Budapest
country: Hungary
city: Debrecen
country: Hungary
city: Zalaegerszeg
country: Hungary
city: Haifa
country: Israel
city: Tel Aviv
country: Israel
city: Milano
country: Italy
city: Modena
country: Italy
city: Pavia
country: Italy
city: Perugia
country: Italy
city: Reggio Emilia
country: Italy
city: Roma
country: Italy
city: Nijmegen
country: Netherlands
city: Gdansk
country: Poland
city: Krakow
country: Poland
city: Lodz
country: Poland
city: Lublin
country: Poland
city: Poznan
country: Poland
city: Szczecin
country: Poland
city: Warszawa
country: Poland
city: Warszawa
country: Poland
city: Wroclaw
country: Poland
city: Barnaul
country: Russian Federation
city: Kazan
country: Russian Federation
city: Kirov
country: Russian Federation
city: Moscow
country: Russian Federation
city: Moscow
country: Russian Federation
city: Obninsk
country: Russian Federation
city: St. Petersburg
country: Russian Federation
city: Bloemfontein
country: South Africa
state: Freestate
city: Pretoria
country: South Africa
state: Gauteng
city: Durban
country: South Africa
state: Kwazulu-Natal
city: Cape Town
country: South Africa
state: Western Cape
city: Cruces/Barakaldo
country: Spain
state: Bilbao
city: Barcelona
country: Spain
city: Madrid
country: Spain
city: Valencia
country: Spain
city: Donetsk
country: Ukraine
city: Kharkiv
country: Ukraine
city: Kiev
country: Ukraine
city: Lviv
country: Ukraine
city: Poltava
country: Ukraine
city: Northwood
country: United Kingdom
state: Middlesex
city: Cardiff
country: United Kingdom
state: South Glamorgan
city: Glasgow
country: United Kingdom
state: Stratchclyde
city: Sutton
country: United Kingdom
state: Surrey
city: Newcastle Upon Tyne
country: United Kingdom
state: Tyne and Wear
city: Birmingham
country: United Kingdom
state: West Midlands
city: Manchester
country: United Kingdom
Study officials:
affiliation: Bayer
name: Bayer Study Director
role: STUDY_DIRECTOR
References:
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citation: Eisen T, Oudard S, Szczylik C, Gravis G, Heinzer H, Middleton R, Cihon F, Anderson S, Shah S, Bukowski R, Escudier B; TARGET Study Group. Sorafenib for older patients with renal cell carcinoma: subset analysis from a randomized trial. J Natl Cancer Inst. 2008 Oct 15;100(20):1454-63. doi: 10.1093/jnci/djn319. Epub 2008 Oct 7.
citation: Bukowski R, Cella D, Gondek K, Escudier B; Sorafenib TARGETs Clinical Trial Group. Effects of sorafenib on symptoms and quality of life: results from a large randomized placebo-controlled study in renal cancer. Am J Clin Oncol. 2007 Jun;30(3):220-7. doi: 10.1097/01.coc.0000258732.80710.05.
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citation: Kane RC, Farrell AT, Saber H, Tang S, Williams G, Jee JM, Liang C, Booth B, Chidambaram N, Morse D, Sridhara R, Garvey P, Justice R, Pazdur R. Sorafenib for the treatment of advanced renal cell carcinoma. Clin Cancer Res. 2006 Dec 15;12(24):7271-8. doi: 10.1158/1078-0432.CCR-06-1249.
citation: Lamuraglia M, Escudier B, Chami L, Schwartz B, Leclere J, Roche A, Lassau N. To predict progression-free survival and overall survival in metastatic renal cancer treated with sorafenib: pilot study using dynamic contrast-enhanced Doppler ultrasound. Eur J Cancer. 2006 Oct;42(15):2472-9. doi: 10.1016/j.ejca.2006.04.023. Epub 2006 Sep 11.
citation: Quintanilha JCF, Geyer S, Etheridge AS, Racioppi A, Hammond K, Crona DJ, Pena CE, Jacobson SB, Marmorino F, Rossini D, Cremolini C, Sanoff HK, Abou-Alfa GK, Innocenti F. KDR genetic predictor of toxicities induced by sorafenib and regorafenib. Pharmacogenomics J. 2022 Dec;22(5-6):251-257. doi: 10.1038/s41397-022-00279-3. Epub 2022 Apr 28.
citation: Quintanilha JCF, Racioppi A, Wang J, Etheridge AS, Denning S, Pena CE, Skol AD, Crona DJ, Lin D, Innocenti F. PIK3R5 genetic predictors of hypertension induced by VEGF-pathway inhibitors. Pharmacogenomics J. 2022 Feb;22(1):82-88. doi: 10.1038/s41397-021-00261-5. Epub 2021 Nov 13.