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Completed

NCT Number: NCT00618982

Sorafenib Dose Escalation in Renal Cell Carcinoma

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.

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Key information

Conditions

Carcinoma, Renal Cell Adenocarcinoma Carcinoma Female Urogenital Diseases Female Urogenital Diseases and Pregnancy Complications Kidney Diseases Kidney Neoplasms Male Urogenital Diseases Neoplasms Neoplasms by Histologic Type Neoplasms by Site Neoplasms, Glandular and Epithelial Urogenital Diseases Urogenital Neoplasms Urologic Diseases Urologic Neoplasms

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

Bordeaux, France

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About this study

Issues on Outcome Measure "Safety and tolerability" will be addressed in the Adverse Events section.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

Sorafenib (Nexavar, BAY43-9006)

Drug

The initial dose of sorafenib will be 400 mg bid administered orally, on a continuous basis. A treatment cycle is considered to be 28 days. Intrapatient dose escalation will occur according to the following schedule, providing no grade 3 or 4 toxicities are observed (except for alopecia, nausea and vomiting); Day 1-28 400 mg bid, Day 29-56 600 mg bid, Day 57 onwards 800 mg bid. Subjects will continue on treatment until progression, unacceptable toxicity, subject withdraws consent or the decision is taken to stop the study following the analysis of response rates.

Primary outcomes

  1. 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.

    Best Response (Response Rate) of a subject was defined as the proportion of patients with confirmed Complete Response (CR) or Partial Response (PR) as their best response observed (by independent central assessment) during trial period assessed according to the Response Evaluation Criteria in Solid Tumors (RECIST version 1.0) criteria. Confirmed CR was defined as disappearance of tumor and PR was defined as a decrease of at least 30% in the sum of tumor lesion sizes.

  2. 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.

    Tumor Response of a subject was defined as the best tumor response observed (by independent central assessment) during trial period assessed according to the Response Evaluation Criteria in Solid Tumors (RECIST version 1.0) criteria. Confirmed Complete Response (CR) was defined as disappearance of tumor, Partial Response (PR) was defined as a decrease of at least 30% in the sum of target lesions, Stable Disease (SD) was defined as steady state of disease, and Progressive Disease (PD) was defined as at least a 20% increase in the sum of measured lesions or appearance of new lesions.

Secondary outcomes

  1. 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.

    AUC(0-10),ss was defined as an area under the plasma concentration versus time curve from time zero to 10 hours post-dose. Parameter was calculated for sorafenib and M2, an active metabolite of sorafenib.

  2. 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.

    AUC(0-12),ss was defined as an area under the plasma concentration versus time curve from time zero to 12 hours post-dose. Parameter was calculated for sorafenib and M2, an active metabolite of sorafenib.

  3. 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.

    Cmax was defined as a maximum plasma concentration at steady-state. Parameter was calculated for sorafenib and M2, an active metabolite of sorafenib.

  4. 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.

    Tmax was defined as a time to maximum concentration at steady-state. Parameter was calculated for sorafenib and M2, an active metabolite of sorafenib.

  5. 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.

    Progression-free survival (PFS) was defined as the time from start of study medication to the first documented disease progression per RECIST (by independent radiological assessment) or clinical progression as per investigator assessment or death due to any cause whichever occurred first. For patients who had not recurred or died at the time of analysis, PFS was censored at their last date of evaluable scan.

  6. 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.

    Time to progression (TTP) was defined as the time from start of study medication to the first documented disease progression per RECIST (by independent radiological assessment) or clinical progression as per investigator assessment whichever occurred first. For patients who had not progressed at the time of analysis or died before progression, TTP was censored at their last date of evaluable scan.

Other outcomes

  1. Tumor Response - mITT 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.

    Tumor Response of a subject was defined as the best tumor response observed (by independent central assessment) during trial period assessed according to the Response Evaluation Criteria in Solid Tumors (RECIST version 1.0) criteria. Confirmed Complete Response (CR) was defined as disappearance of tumor, Partial Response (PR) was defined as a decrease of at least 30% in the sum of target lesions, Stable Disease (SD) was defined as steady state of disease, and Progressive Disease (PD) was defined as at least a 20% increase in the sum of measured lesions or appearance of new lesions.

  2. Disease Control - mITT 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.

    Disease Control (DC) of a subject was defined as the proportion of patients with confirmed Complete Response (CR), Partial Response (PR) or Stable Disease (SD) as their best response observed (by independent central assessment) during trial period assessed according to the Response Evaluation Criteria in Solid Tumors (RECIST version 1.0) criteria. Confirmed CR was defined as disappearance of tumor, PR was defined as a decrease of at least 30% in the sum of tumor lesion sizes, and SD was defined as steady state of disease.

Sponsors and collaborators

Lead sponsor

Bayer

Industry

Registry information

Official study title

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.

Important dates

Study start
2008
Primary completion
2009
Study completion
2011
First posted
Feb 20, 2008
Registry last updated
Dec 24, 2015

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

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This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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