Sorafenib Long Term Extension Program

Study Overview
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Brief Summary
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The primary purpose of program was to enable patients, currently receiving sorafenib (Nexavar) in a Bayer/Onyx sponsored clinical trial, to continue sorafenib treatment after their respective study had met its primary endpoint and/or had reached the end as defined in the original protocol. Patients were able to continue treatment until (i) the treating physician felt the patient was no longer benefiting from the treatment or (ii) the treatment becomes commercially available and reimbursed for the respective indication as applicable in the country in which the patient lived and the patient could obtain suitable amounts of drug for treatment through standard mechanisms of commercial availability (ie, there should be no interruption in the patient's treatment schedule when switching to commercially available product) or (iii) the patient could join a Post-Trial-Access Program, another study or can receive sorafenib through any other mechanism (e.g. local access program) in accordance with local legal and compliance rules, with no cost to the patient with respect to sorafenib. An additional objective was the assessment of the safety of Nexavar or Nexavar combination treatment.

Official Title
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Sorafenib Long Term Extension Program

Conditions
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Neoplasms

Intervention / Treatment
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* Drug: Sorafenib (Nexavar, BAY43-9006)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients, who are participating in a previous Bayer/Onyx sponsored study that has reached its endpoint (statistical and regulatory or study end), and who are, in the opinion of the Investigator, expected to continue to have an overall positive benefit/risk from continuing treatment. Patients who have signed informed consent for this long term extension program. Women of childbearing potential and men must agree to use adequate contraception prior to study entry and for the duration of study participation, including the 30 days period after last study drug dosing. The investigator should advise the patient how to achieve an adequate contraception. Women of childbearing potential who have a negative pregnancy test within 7 days of the first dose of sorafenib in this long term extension program. Patient is receiving sorafenib (Nexavar) as a monotherapy in their originating protocol. Patients who were being treated with sorafenib (Nexavar) in combination with other chemotherapies in the original study, but continued on single agent sorafenib (Nexavar) after discontinuation of the combination agent will be eligible. Patient who are receiving concurrent combination with sorafenib (Nexavar) and TACE (transarterial chemoembolization) in their originating study will be eligible. Patients who are receiving concurrent combination with sorafenib (Nexavar) and capecitabine in their originating Study 12444 (RESILIENCE) will be eligible. Patients who are receiving concurrent combination with sorafenib (Nexavar) and erlotinib in their originating study 12917 (SEARCH) were eligible. Patients who have completed the End of Treatment assessments in their originating study. Every effort should be made to conduct the End of Treatment visit such that the patient does not have any interruption of sorafenib dosing. Exclusion Criteria: Any condition that is unstable or that could jeopardize the safety of the patient (please refer to the Investigator Brochure and product labeling safety sections). History of cardiac disease: congestive heart failure > New York Heart Association (NYHA) Class 2 or uncontrolled hypertension. Myocardial infarction (MI) within the last 3 months. Symptomatic metastatic brain or meningeal tumors . Previous or concurrent cancer that is distinct in primary site or histology from the cancer being evaluated in this study EXCEPT cervical carcinoma in situ, treated basal cell carcinoma, superficial bladder tumors ( Ta, Tis &T1) or any cancer curatively treated > 5 years prior to study entry. Patients with seizure disorder requiring medication (such as steroid anti-epileptics). Substance abuse, medical, psychological or social conditions that may interfere with the patient's participation in the study or evaluation of the study results. Any condition which could jeopardise the safety of the patient and his/her compliance in the study. Excluded therapies and medications, previous and concomitant: Concurrent anti-cancer chemotherapy, except transarterial chemoembolization (TACE) and capecitabine Concurrent immunotherapy (including monoclonal antibodies), during or within 30 days prior to start of study drug Concurrent hormonal therapy, except for bisphosphonates,during or within 30 days prior to start of study drug Concomitant Rifampicin and St John's Wort (Warfarin may be used only with very close monitoring) Radiotherapy during study or within 3 weeks of start of study drug. [Palliative radiotherapy will be allowed] Concomitant use of potent inhibitors of CYP3A4 including ketoconazole, itraconazole and ritonavir. Consumption of grapefruit juice should also be avoided.

Ages Eligible for Study
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Minimum Age: 16 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Sorafenib (Nexavar, BAY43-9006)<br>Participants receive single-agent sorafenib at the same dose and schedule as in their original clinical trials. | Drug: Sorafenib (Nexavar, BAY43-9006)<br>* At the same dose and schedule as in the participants' original clinical trials<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Sorafenib Treatment Duration Within STEP | Treatment duration was calculated in days as the date of the last dose of any study treatment minus date of the first dose of any study treatment plus one day. | From the date of the first sorafenib dose until the date of the last sorafenib dose, with a mean duration of 25 months and max duraton of 153.8 months | 
| Number of Participants With New Treatment-emergent Adverse Events (TEAEs) | An adverse event (AE) was any untoward medical occurrence in a participant or clinical investigation participant administered with a pharmaceutical product. The adverse event did not necessarily have to have a causal relationship with this treatment. A serious adverse event (SAE) was any untoward medical occurrence that at any dose: resulted in death; was life-threatening; required in-patient hospitalization or prolongation of existing hospitalization; resulted in persistent or significant disability or incapacity; was a congenital anomaly or birth defect; was an important medical event. A new treatment-emergent adverse event (TEAE) was any AE that had a start date on or after ICF date in STEP and up to 30 days after the last sorafenib dose. A drug-related new TEAE was any new TEAE that had a causal relationship with the study treatment as assessed by the investigator. | From signing the informed consent form (ICF) in STEP until 30 days after the last sorafenib dose, with a mean duration of 26 months | 
| Number of Participants With New TEAEs of CTCAE Grades 3 or Higher by Worst CTCAE Grade | An adverse event (AE) was any untoward medical occurrence in a participant or clinical investigation participant administered with a pharmaceutical product. The AE did not necessarily have to have a causal relationship with this treatment. A new treatment-emergent adverse event (TEAE) was any AE that had a start date on or after ICF date in STEP and up to 30 days after the last sorafenib dose. The intensity or severity of AEs were graded using the National Cancer Institute-Common Terminology Criteria, Version 3.0 (NCI-CTC v. 3.0). The Common Terminology Criteria for AE (CTCAE) are a set of criteria for the standardized classification of adverse effects of drugs used in cancer therapy. It uses a range of grades from 1 to 5. Specific conditions and symptoms may have values or descriptive comment for each level, but the general guideline is: Grade 1 - mild; Grade 2 - moderate; Grade 3 - severe; Grade 4 - life-threatening; Grade 5 - death. | From signing the ICF in STEP until 30 days after the last sorafenib dose, with a mean duration of 26 months | 
| Number of Participants With Study Drug-related New TEAEs of CTCAE Grades 3 or Higher by Worst CTCAE Grade | An adverse event (AE) was any untoward medical occurrence in a participant or clinical investigation participant administered with a pharmaceutical product. The AE did not necessarily have to have a causal relationship with this treatment. A new treatment-emergent AE (TEAE) was any AE that had a start date on or after ICF date in STEP and up to 30 days after the last sorafenib dose. A drug-related new TEAE was a new TEAE that had a causal relationship with the study treatment as assessed by the investigator. The intensity or severity of AEs were graded using the National Cancer Institute-Common Terminology Criteria (CTC v3). The Common Terminology Criteria for AE (CTCAE) are a set of criteria for the standardized classification of adverse effects of drugs used in cancer therapy. It uses a range of grades from 1 to 5. The general guideline is: Grade 1 - mild; Grade 2 - moderate; Grade 3 - severe; Grade 4 - life-threatening; Grade 5 - death. | From signing the ICF in STEP until 30 days after the last sorafenib dose, with a mean duration of 26 months | 
| Number of Participants With All Adverse Events | An adverse event (AE) was any untoward medical occurrence in a participant or clinical investigation participant administered with a pharmaceutical product. The AE did not necessarily have to have a causal relationship with this treatment. A drug-related AE was any AE that had a causal relationship with the study treatment as assessed by the investigator. All AEs in STEP were the combination of AEs ongoing from feeder studies and new TEAEs. | From signing the ICF in STEP until 30 days after the last sorafenib dose, with a mean duration of 26 months | 
| Number of Participants With All Adverse Events of CTCAE Grades 3 or Higher by Worst CTCAE Grade | An adverse event (AE) was any untoward medical occurrence in a participant or clinical investigation participant administered with a pharmaceutical product. The AE did not necessarily have to have a causal relationship with this treatment. All AEs in STEP were the combination of AEs ongoing from feeder studies and new TEAEs. The intensity or severity of AEs were graded using the National Cancer Institute-Common Terminology Criteria, Version 3.0 (NCI-CTC v. 3.0). The Common Terminology Criteria for AE (CTCAE) are a set of criteria for the standardized classification of adverse effects of drugs used in cancer therapy. It uses a range of grades from 1 to 5. Specific conditions and symptoms may have values or descriptive comment for each level, but the general guideline is: Grade 1 - mild; Grade 2 - moderate; Grade 3 - severe; Grade 4 - life-threatening; Grade 5 - death. | From signing the ICF in STEP until 30 days after the last sorafenib dose, with a mean duration of 26 months | 
| Number of Participants With Study Drug-related All Adverse Events of CTCAE Grades 3 or Higher by Worst CTCAE | An adverse event (AE) was any untoward medical occurrence in a participant or clinical investigation participant administered with a pharmaceutical product. The AE did not necessarily have to have a causal relationship with this treatment. A drug-related AE was any AE that had a causal relationship with the study treatment as assessed by the investigator. All AEs in STEP was a combination of AEs ongoing from feeder studies and new TEAEs. The intensity or severity of AEs were graded using the National Cancer Institute-Common Terminology Criteria, Version 3.0 (NCI-CTC v. 3.0). The Common Terminology Criteria for AE (CTCAE) are a set of criteria for the standardized classification of adverse effects of drugs used in cancer therapy. It uses a range of grades from 1 to 5. Specific conditions and symptoms may have values or descriptive comment for each level, but the general guideline is: Grade 1 - mild; Grade 2 - moderate; Grade 3 - severe; Grade 4 - life-threatening; Grade 5 - death. | From signing the ICF in STEP until 30 days after the last sorafenib dose, with a mean duration of 26 months | 
| Number of Deaths With Primary Cause of Death | Primary cause of death included: any cause; progressive disease; toxicity due to study treatment (with at least one AE with outcome death); other (unspecified) or missing cause. | From signing the ICF in STEP until completion or discontinuation of the study, with a mean duration of 26 months | 
| Number of Participants With Abnormal Hematological and Biochemical Laboratory Values by Worst CTCAE Grade | Hematology and blood chemistry values were summarized according to their worst CTCAE grade, where applicable. Hematology and blood chemistry values were graded based on the applicable laboratory threshold values outlined in NCI CTCAE version 3.0. Participants with a specific laboratory value that were not graded are not included in the table. CTCAE grade was set to not graded if the reference ranges or other information necessary to derive grades were unavailable or result had a special character (such as > or < ). The Common Terminology Criteria for Adverse Events (CTCAE) are a set of criteria for the standardized classification of adverse effects of drugs used in cancer therapy. It uses a range of grades from 1 to 5. Specific conditions and symptoms may have values or descriptive comment for each level, but the general guideline is: Grade 1 - mild; Grade 2 - moderate; Grade 3 - severe; Grade 4 - life-threatening; Grade 5 - death. | From signing the ICF in STEP until 30 days after the last sorafenib dose, with a mean duration of 26 months | 
| Number of Participants With ECOG Performance Status by 6-months Time Intervals | Eastern cooperative oncology group (ECOG) performance status: 0 = Fully active, able to carry on all pre-disease performance without restriction; 1 = Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature, e.g. light house work, office work; 2 = Ambulatory and capable of all self-care but unable to carry out any work activities, up and about more than 50% of waking hours; 3 = Capable of only limited self-care, confined to bed or chair more than 50% of waking hours; 4 = Completely disabled, cannot carry on any self-care, totally confined to bed or chair; 5 = Dead | Up to 156 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Cancer, Sorafenib, Extension program