Study Completed

Carcinoma, Renal Cell

Bayer Identifier:

12913

ClinicalTrials.gov Identifier:

NCT00618982

EudraCT Number:

2007-004875-21

EU CT Number:

Not Available

Sorafenib Dose Escalation in Renal Cell Carcinoma

Trial purpose

Sorafenib is a new drug, which is approved under the brand name Nexavar for the treatment of advanced kidney cancer. It is also currently being tested in various other cancers. Sorafenib works by stopping the development of new cancer cells and new blood vessels. By stopping the growth of new blood vessels around a tumor, it is believed that sorafenib prevents the growth of kidney cancer tumors.
This is an "open-label" study which means that the patient, the doctor and Bayer Healthcare will know what tablets the patient is taking. All patients in this study will receive sorafenib tablets. Sorafenib is taken orally as a tablet (two tablets are taken twice a day). Treatment with sorafenib will continue until the patient’s tumor grows larger or spreads further or if the patient has intolerable side effects. The dose of sorafenib that the patient will receive in the study will increase at certain points during the patient’s treatment, as long as the patient is not experiencing side effects and the patient’s tumor has not grown.

Key Participants Requirements

Sex

Both

Age

18 Years

Inclusion Criteria
- Age > 18 years.
- Metastatic clear cell RCC (renal cell carcinoma)
- Subjects with at least one uni-dimensional
measurable lesion.
- Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1
- Memorial Sloan Kettering Cancer Center (MSKCC) good or intermediate category
- Life expectancy of at least 12 weeks.
- Adequate bone marrow, liver and renal function as assessed by the following laboratory requirements to be conducted within 7 days prior to treatment
- Signed informed consent must be obtained prior to any study specific procedures.
- Subjects must have received no prior systemic anticancer therapy for the treatment of their renal cell carcinoma
- Prior total nephrectomy
Exclusion Criteria
- History of cardiac disease
- History of human immunodeficiency virus (HIV) infection or chronic hepatitis
B or C
- Active clinically serious infections (> grade 2 National Cancer
Institute-Common Terminology Criteria for Adverse Events [NCI-CTCAE] version 3.0)
- Symptomatic metastatic brain or meningeal tumors unless the subject is > 6 months from definitive therapy, has a negative imaging study within 4 weeks of study entry and is clinically stable with respect to the tumor at the time of study entry.
- Subjects with evidence or history of bleeding diathesis
- Deep vein thrombosis and/or pulmonary embolus within 12 months of the start of treatment.
- Delayed healing of wounds, ulcers or bone fractures
- Subjects with pre-existing thyroid abnormality whose thyroid function cannot be maintained within the normal range by medication
- Subjects undergoing renal dialysis
- Pregnant or breast-feeding subjects. Women of childbearing potential must have a negative serum pregnancy test performed within 7 days prior to the start of treatment. Both men and women enrolled in this trial must use adequate barrier birth control measures during the course of the trial and three months after the completion of trial.
- Prior adjuvant sorafenib is excluded.
- Radiotherapy during study or within 3 weeks of start of study drug
- Major surgery within 4 weeks of start of study
- Investigational drug therapy outside of this trial during or within 4 weeks of study entry

Trial summary

Enrollment Goal

Trial Dates

February 2008 - January 2011

Phase

Phase 2

Could I Receive a placebo

Products

Nexavar (Sorafenib, BAY43-9006)

Accepts Healthy Volunteer

Where to participate

Status	Institution	Location
Completed	Johannes-Gutenberg-Universität Mainz	Mainz, 55131, Germany
Terminated	Klinikum der Eberhard-Karls-Universität Tübingen	Tübingen, 72076, Germany
Terminated	Universitätsklinik Gießen und Marburg GmbH	Marburg, 35043, Germany
Completed	Kliniken der Medizinischen Hochschule Hannover	Hannover, 30625, Germany
Completed	Christie Hospital	Greater Manchester, M20 4BX, United Kingdom
Completed	Beatson West of Scotland Cancer Centre	Glasgow, G12 0YN, United Kingdom
Completed	Velindre Hospital	Cardiff, CF14 7TB, United Kingdom
Completed	Hôpital de la Timone - Marseille	MARSEILLE, 13385, France
Completed	Hôpital Saint André - Bordeaux	BORDEAUX, 33000, France
Completed	Centre Hospitalier Départemental-La Roche sur Yon	LA ROCHE SUR YON, 85925, France
Completed	Centrum Onkologii - Instytut im. M.Sklodowskiej-Curie	Warszawa, 02-781, Poland
Terminated	Uniwersytecki Szpital Kliniczny im. J. Mikulicza-Radeckiego	Wroclaw, 50 - 556, Poland
Completed	IRCCS Istituto Nazionale Tumori	Milano, 20133, Italy
Completed	Klinikum der Friedrich-Schiller-Universität Jena	Jena, 07740, Germany
Completed	Royal Marsden Hospital (London)	London, SW3 6JJ, United Kingdom
Completed	Hôpital Bretonneau - Tours	TOURS, 37044, France
Completed	Centre René Gauducheau - Nantes	NANTES, 44805, France
Completed	Hôpital Saint Louis - Paris	PARIS CEDEX 10, 75475, France
Completed	Wojskowy Instytut Medyczny	Warszawa, 04-141, Poland
Completed	NZOZ ONKO-MED	Olsztyn, 10-226, Poland
Completed	IRCCS Centro di Riferimento Oncologico - CRO	Aviano, 33081, Italy
Completed	IRCCS Policlinico San Matteo	Pavia, 27100, Italy

Primary Outcome

Best Response - mITT (modified intent-to-treat) population
Time Frame:
Radiological assessments were performed every 8 weeks (2 cycles) from start of the treatment. After completion of 6 cycles of treatment at the highest tolerated dose level, assessments were performed every 12 weeks for up to 34 months.
Safety Issue:
No
Tumor Response - ITT (intent to treat) population
Time Frame:
Radiological assessments were performed every 8 weeks (2 cycles) from start of the treatment. After completion of 6 cycles of treatment at the highest tolerated dose level, assessments were performed every 12 weeks for up to 34 months.
Safety Issue:
No

Secondary Outcome

Pharmacokinetics (PK) analysis – Area under the drug concentration-time curve from time zero to 10 hours postdose (AUC(0-10),ss)
Time Frame:
Blood samples were collected at screening (blank) and on day 28 of the first cycle completed at each dose level. Samples were drawn at the following time points in relation to morning dose of sorafenib: pre-dose, 2, 4, 6, 8 and 10 hours post-dose.
Safety Issue:
No
Pharmacokinetics (PK) analysis – Area under the drug concentration-time curve from time zero to 12 hours postdose (AUC(0-12),ss)
Time Frame:
Blood samples were collected at screening (blank) and on day 28 of the first cycle completed at each dose level. Samples were drawn at the following time points in relation to morning dose of sorafenib: pre-dose, 2, 4, 6, 8, 10 and 12 hours post-dose.
Safety Issue:
No
Pharmacokinetics (PK) analysis – Maximum observed concentration in plasma (Cmax)
Time Frame:
Blood samples were collected at screening (blank) and on day 28 of the first cycle completed at each dose level. Samples were drawn at the following time points in relation to morning dose of sorafenib: pre-dose, 2, 4, 6, 8, 10 and 12 hours post-dose.
Safety Issue:
No
Pharmacokinetics (PK) analysis – Time to maximum concentration (Tmax)
Time Frame:
Blood samples were collected at screening (blank) and on day 28 of the first cycle completed at each dose level. Samples were drawn at the following time points in relation to morning dose of sorafenib: pre-dose, 2, 4, 6, 8, 10 and 12 hours post-dose.
Safety Issue:
No
Progression-free Survival (PFS)
Time Frame:
Radiological assessments were performed every 8 weeks (2 cycles) from start of the treatment. After completion of 6 cycles of treatment at the highest tolerated dose level, assessments were performed every 12 weeks for up to 34 months.
Safety Issue:
No
Time to Progression (TTP)
Time Frame:
Radiological assessments were performed every 8 weeks (2 cycles) from start of the treatment. After completion of 6 cycles of treatment at the highest tolerated dose level, assessments were performed every 12 weeks for up to 34 months.
Safety Issue:
No

Trial design

A Phase II, Multi-centre, Open-label Study to Assess the Efficacy, Safety, Tolerability and Pharmacokinetics of Intrapatient Dose Escalation of Sorafenib as First Line Treatment for Metastatic Renal Cell Carcinoma.

Trial Type

Interventional

Intervention Type

Drug

Trial Purpose

Treatment

Allocation

N/A

Blinding

Open Label

Assignment

Single Group Assignment

Trial Arms

Additional Information

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