Carcinoma, Renal CellPhase 3NCT00073307
Study of BAY43-9006 in Patients With Unresectable and/or Metastatic Renal Cell Cancer
A Phase 3 study testing Sorafenib (Nexavar, BAY43-9006) in people with Carcinoma, Renal Cell, run by Bayer at 121 sites in 19 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Carcinoma, Renal Cell
- What is being tested?
- Sorafenib (Nexavar, BAY43-9006)
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 903 participants
- Where
- 121 sitesin 19 countries
- Study dates
- Nov 2003to Apr 2010
- Phase
- Phase 3
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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)
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- 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
Trial locations and contacts
121 sites in 19 countries.
121 sites in 19 countries
United States31 sites
Study site
Atlanta, Georgia, 30309
Study site
Aurora, Colorado, 80045
Study site
Boston, Massachusetts, 02215
Study site
Brooklyn, New York, 11220
Study site
Canton, Ohio, 44718
Study site
Chicago, Illinois, 60637
Study site
Cleveland, Ohio, 44195
Study site
Columbia, Missouri, 65203-3244
Study site
Dallas, Texas, 75246
Study site
Dayton, Ohio, 45429
Study site
Frederick, Maryland, 21701
Study site
Hamden, Connecticut, 06518
Study site
Lafayette, Louisiana, 70506
Study site
Laredo, Texas, 78041
Study site
Los Angeles, California, 90033
Study site
Los Angeles, California, 90057
Study site
Louisville, Kentucky, 40202
Study site
Milwaukee, Wisconsin, 53226-3596
Study site
Minneapolis, Minnesota, 55455
Study site
New York, New York, 10032
Study site
Philadelphia, Pennsylvania, 19107-5096
Study site
Portland, Oregon, 97239
Study site
Richmond, Virginia, 23229
Study site
Sacramento, California, 95817
Study site
Salt Lake City, Utah, 84132
Study site
San Antonio, Texas, 78212
Study site
Seattle, Washington, 98101
Study site
Spartanburg, South Carolina, 29303
Study site
St Louis, Missouri, 63110-1093
Study site
The Bronx, New York, 10466-2604
Study site
Tucson, Arizona, 85712
France10 sites
Study site
Bordeaux, 33000
Study site
Caen, 14076
Study site
Lille, 59020
Study site
Lyon, 69008
Study site
Marseille, 13273
Study site
Nantes, 44805
Study site
Paris, 75908
Study site
Strasbourg, 67091
Study site
Toulouse, 31052
Study site
Villejuif, 94805
Germany10 sites
Study site
Berlin, State of Berlin, 10967
Study site
Darmstadt, Hesse, 64276
Study site
Dresden, Saxony, 01307
Study site
Düsseldorf, North Rhine-Westphalia, 40225
Study site
Frankfurt am Main, Hesse, 60488
Study site
Hamburg, Free and Hanseatic City of Hamburg, 20246
Study site
Mannheim, Baden-Wurttemberg, 68167
Study site
München, Bavaria, 81377
Study site
Regensburg, Bavaria, 93042
Study site
Ulm, Baden-Wurttemberg, 89075
Poland9 sites
Study site
Gdansk, 80-210
Study site
Krakow, 31-115
Study site
Lodz, 93-509
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Lublin, 20-090
Study site
Poznan, 61-878
Study site
Szczecin, 70-111
Study site
Warsaw, 02-781
Study site
Warsaw, 04-141
Study site
Wroclaw, 50-043
Russia7 sites
Study site
Barnaul, 656049
Study site
Kazan', 420029
Study site
Kirov, 610021
Study site
Moscow, 115478
Study site
Moscow, 125284
Study site
Obninsk, 249036
Study site
Saint Petersburg, 198255
United Kingdom7 sites
Study site
Birmingham, West Midlands, B15 2TT
Study site
Cardiff, South Glamorgan, CF14 2TL
Study site
Glasgow, Stratchclyde, G11 6NT
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Manchester, Manchester, M20 4BX
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Newcastle upon Tyne, Tyne and Wear, NE4 6BE
Study site
Northwood, Middlesex, HA6 2RN
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Sutton, Surrey, SM2 5PT
Australia6 sites
Study site
Camperdown, New South Wales, 2050
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Garran, Australian Capital Territory, 2605
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Heidelberg, Victoria, 3084
Study site
Liverpool, New South Wales, 2170
Study site
Westmead, New South Wales, 2145
Study site
Wodonga, Victoria, 0390
Italy6 sites
Study site
Milan, 20133
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Modena, 41124
Study site
Pavia, 27100
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Perugia, 06122
Study site
Reggio Emilia, 42100
Study site
Roma, 00144
Canada5 sites
Study site
Edmonton, Alberta, T6G 1Z2
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Hamilton, Ontario, L8V 5C2
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London, Ontario, N6A 4L6
Study site
Montreal, Quebec, H3T 1E2
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Toronto, Ontario, M5G 2M9
Ukraine5 sites
Study site
Donetsk, 83092
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Kharkiv, 61024
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Kiev, 115
Study site
Lviv, 79031
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Poltava, 36024
Argentina4 sites
Study site
Capital Federal-Buenos Aires, C1426ANZ
Study site
Mendoza, 5500
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Rosario, Santa Fe Province, S2000DSK
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Santa Fe, Santa Fe Province, S3000FFV
Hungary4 sites
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Budapest, 1032
Study site
Budapest, 1121
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Debrecen, 4004
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Zalaegerszeg, 8900
South Africa4 sites
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Bloemfontein, Freestate, 9300
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Cape Town, Western Cape, 7500
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Durban, KwaZulu-Natal, 4001
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Pretoria, Gauteng
Spain4 sites
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Barcelona, Barcelona, 08035
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Cruces/Barakaldo, Bilbao, 48903
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Madrid, Madrid, 28040
Study site
Valencia, Valencia, 46009
Brazil3 sites
Study site
Curitiba, Paraná, 81520-060
Study site
Porto Alegre, Rio Grande do Sul, 90020-060
Study site
Porto Alegre, Rio Grande do Sul, 90619900
Belgium2 sites
Study site
Bruxelles - Brussel, 1000
Study site
Bruxelles - Brussel, 1090
About this study
Official title: A Phase III Randomized Study of BAY43-9006 in Patients With Unresectable and/or Metastatic Renal Cell Cancer.
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.
Read the detailed description
Overall Survival (OS), Patient-reported outcome (PRO)
- Conditions
- Carcinoma, Renal Cell
- Being tested
- Sorafenib (Nexavar, BAY43-9006), Placebo
- Keywords
- Renal Cell Cancer (RCC), Cancer
- Medical subject headings
- Carcinoma, Renal Cell, Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Sorafenib (Nexavar, BAY43-9006)Drug
Multi Kinase Inhibitor
PlaceboDrug
Placebo
| Study group | Role | What they receive |
|---|---|---|
| Sorafenib (Nexavar, BAY43-9006) | Experimental | Sorafenib was to be orally administered as 2 x 200 mg tablets bid (twice daily). Dose modification due to toxicity was permitted. Receives: Drug: Sorafenib (Nexavar, BAY43-9006) |
| Placebo | Placebo comparator | Placebo tablets matching in appearance were to be orally administered twice a day. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Final Overall Survival (OS) - Primary Analysis in the ITT (Intent To Treat) Population
Overall survival determined as the time (days) from the date of randomization at start of study to the date of death, due to any cause. Outcome measure was assessed regularly, i.e. every 3 weeks for the first 24 weeks during treatment and every 4 weeks thereafter and approximately every 3 months during post-treatment.
Measured: From start of randomization of the first subject (1Dec2003) until the data cut-off (8Sep2006) for the final OS analysis, approximately 33 months later
Final Overall Survival - Secondary Analysis (Placebo Data Censored at 30June2005) in the ITT Population
Overall survival determined as the time (days) from the date of randomization at start of study to the date of death, due to any cause. Outcome measure was assessed regularly, i.e. every 3 weeks for the first 24 weeks during treatment and every 4 weeks thereafter and approximately every 3 months during post-treatment.
Measured: 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 (4)
Final Progression-Free Survival (PFS) - Independent Radiological Review
PFS determined as the time (days) from the date of randomization at start of study to the actual date of disease progression (PD) (radiological or clinical) or death due to any cause, if death occurred before PD. Outcome measure was assessed approximately every 8 weeks using RECIST v1.0 criteria by independent radiologic review. Radiological PD defined as at least 20% increase in sum of longest diameter (LD) of measured lesions taking as reference smallest sum LD recorded since treatment started or appearance of new lesions.
Measured: From start of randomization of the first subject (1Dec2003) until the data cut-off (28Jan2005), approximately 14 months later, tumors assessed every 8 weeks.
Best Overall Response - Independent Radiological Review
Best overall response was determined according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.0 by independent radiologic review. Categories: complete response (CR, tumor disappears), partial response (PR, sum of lesion sizes decreased), stable disease (SD, steady state of disease), progressive disease (PD, sum of lesion sizes increased) and not evaluated.
Measured: From start of randomization of the first subject (1Dec2003) until the data cut-off (28Jan2005), approximately 14 months later, tumors assessed every 8 weeks.
Health-related Quality of Life (HRQOL) by FKSI-10 (Functional Assessment of General Therapy Kidney Symptom Index 10) Assessment
Primary Analysis for FKSI-10 patient-reported outcome (PRO) measure defined as longitudinal analysis of mean score over the first 5 treatment cycles. FKSI-10 patient responses for each question range from "0=not at all" to "4=very much" and after reverse coding the range of values for FKSI-10 total score is from 0 to 40; higher score represents better HRQOL.
Measured: 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.
Health-related Quality of Life (HRQOL) by Physical Well-Being (PWB) Score of the FACT-G (Functional Assessment of Cancer Therapy-General Version) Assessment
Primary Analysis for FACT-G (using PWB score) patient-reported outcome (PRO) measure defined as longitudinal analysis of mean score over the first 5 treatment cycles. FACT-G (PWB score) patient responses for each question range from "0=not at all" to "4=very much" and after reverse coding the total FACT-G (PWB score) range of values is from 0 to 28; higher score represents better HRQOL.
Measured: 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.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Nov 2003 (estimated)
- Study startNov 2003
- Primary completionSep 2006
- Study completionApr 2010
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (13)Papers the sponsor has linked to this study.
- Other trials for Carcinoma, Renal CellStudies of the same condition, open and under way.
- More trials run by BayerThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 903 participants (actual)
Sponsor and investigators
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00073307
- Sponsor's protocol ID
- 11213
- Status last verified
- Jan 2014
- First submitted
- 19 Nov 2003
- Last updated
- 6 Feb 2014
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Antoun S, Birdsell L, Sawyer MB, Venner P, Escudier B, Baracos VE. Association of skeletal muscle wasting with treatment with sorafenib in patients with advanced renal cell carcinoma: results from a placebo-controlled study. J Clin Oncol. 2010 Feb 20;28(6):1054-60. doi: 10.1200/JCO.2009.24.9730. Epub 2010 Jan 19.
PubMed 20085939Bellmunt J, Eisen T, Fishman M, Quinn D. Experience with sorafenib and adverse event management. Crit Rev Oncol Hematol. 2011 Apr;78(1):24-32. doi: 10.1016/j.critrevonc.2010.03.006. Epub 2010 Apr 18.
PubMed 20399677Massard C, Zonierek J, Gross-Goupil M, Fizazi K, Szczylik C, Escudier B. Incidence of brain metastases in renal cell carcinoma treated with sorafenib. Ann Oncol. 2010 May;21(5):1027-31. doi: 10.1093/annonc/mdp411. Epub 2009 Oct 22.
PubMed 19850637Negrier S, Jager E, Porta C, McDermott D, Moore M, Bellmunt J, Anderson S, Cihon F, Lewis J, Escudier B, Bukowski R. Efficacy and safety of sorafenib in patients with advanced renal cell carcinoma with and without prior cytokine therapy, a subanalysis of TARGET. Med Oncol. 2010 Sep;27(3):899-906. doi: 10.1007/s12032-009-9303-z. Epub 2009 Sep 12.
PubMed 19757215Pena C, Lathia C, Shan M, Escudier B, Bukowski RM. Biomarkers predicting outcome in patients with advanced renal cell carcinoma: Results from sorafenib phase III Treatment Approaches in Renal Cancer Global Evaluation Trial. Clin Cancer Res. 2010 Oct 1;16(19):4853-63. doi: 10.1158/1078-0432.CCR-09-3343. Epub 2010 Jul 22.
PubMed 20651059Escudier B, Eisen T, Stadler WM, Szczylik C, Oudard S, Staehler M, Negrier S, Chevreau C, Desai AA, Rolland F, Demkow T, Hutson TE, Gore M, Anderson S, Hofilena G, Shan M, Pena C, Lathia C, Bukowski RM. Sorafenib for treatment of renal cell carcinoma: Final efficacy and safety results of the phase III treatment approaches in renal cancer global evaluation trial. J Clin Oncol. 2009 Jul 10;27(20):3312-8. doi: 10.1200/JCO.2008.19.5511. Epub 2009 May 18.
PubMed 19451442Eisen 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.
PubMed 18840822Bukowski 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.
PubMed 17551296Escudier B, Eisen T, Stadler WM, Szczylik C, Oudard S, Siebels M, Negrier S, Chevreau C, Solska E, Desai AA, Rolland F, Demkow T, Hutson TE, Gore M, Freeman S, Schwartz B, Shan M, Simantov R, Bukowski RM; TARGET Study Group. Sorafenib in advanced clear-cell renal-cell carcinoma. N Engl J Med. 2007 Jan 11;356(2):125-34. doi: 10.1056/NEJMoa060655.
PubMed 17215530Kane 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.
PubMed 17189398Lamuraglia 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.
PubMed 16965911Quintanilha 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.
PubMed 35484400Quintanilha 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.
PubMed 34775477