Sorafenib Long Term Extension Program (STEP)

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.

Study Overview

• Status: Completed
• Conditions: Neoplasms
• Intervention / Treatment: Drug: Sorafenib (Nexavar, BAY43-9006)

• Study Type: Interventional
• Enrollment (Actual): 206
• Phase: Phase 3

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Randwick, New South Wales, Australia, 2031
• Belgium
  • Bruxelles - Brussel, Belgium, 1200
  • Charleroi, Belgium, 6000
• Brazil
  • Sao Paulo, Brazil, 01246-903
• Bulgaria
  • Plovdiv, Bulgaria, 4002
  • Varna, Bulgaria, 9010
• Canada
  • Alberta
    • Calgary, Alberta, Canada, T2N 4N1
    • Edmonton, Alberta, Canada, T6G 1Z2
  • Ontario
    • Toronto, Ontario, Canada, M5G 2M9
    • Toronto, Ontario, Canada, M5G 2C4
  • Quebec
    • Montreal, Quebec, Canada, H3A 1A1
    • Montreal, Quebec, Canada, H3T 1E2
    • Montreal, Quebec, Canada, H3G 1A4
• China
  • Beijing, China, 100021
  • Shanghai, China, 200030
  • Guangdong
    • Guangzhou, Guangdong, China, 510080
  • Shanxi
    • Xi'an, Shanxi, China, 710032
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310022
• Colombia
  • Santander
    • Floridablanca, Santander, Colombia
• France
  • Bordeaux, France, 33000
• Germany
  • Berlin, Germany, 12200
  • Hamburg, Germany, 20246
  • Bayern
    • Gauting, Bayern, Germany, 82131
    • Regensburg, Bayern, Germany, 93042
  • Nordrhein-Westfalen
    • Essen, Nordrhein-Westfalen, Germany, 45239
  • Schleswig-Holstein
    • Grosshansdorf, Schleswig-Holstein, Germany, 22927
• Hong Kong
  • Hong Kong, Hong Kong
• Italy
  • Emilia-Romagna
    • Bologna, Emilia-Romagna, Italy, 40138
    • Reggio Emilia, Emilia-Romagna, Italy, 42123
  • Lombardia
    • Milano, Lombardia, Italy, 20133
    • Milano, Lombardia, Italy, 20089
    • Milano, Lombardia, Italy, 20122
    • Pavia, Lombardia, Italy, 27100
  • Piemonte
    • Torino, Piemonte, Italy, 10043
  • Toscana
    • Pisa, Toscana, Italy, 56126
    • Siena, Toscana, Italy, 53100
  • Umbria
    • Perugia, Umbria, Italy, 06132
• Korea, Republic of
  • Daegu, Korea, Republic of, 700721
  • Seoul, Korea, Republic of, 06351
  • Seoul, Korea, Republic of, 03722
  • Seoul Teugbyeolsi
    • Seoul, Seoul Teugbyeolsi, Korea, Republic of, 03080
• New Zealand
  • Auckland, New Zealand, 1023
• Poland
  • Gdansk, Poland, 80-219
  • Poznan, Poland, 61-848
  • Szczecin, Poland, 70-111
  • Warszawa, Poland, 02-781
  • Warszawa, Poland, 04-141
  • Wroclaw, Poland, 50 - 556
• Spain
  • Alicante, Spain, 03010
  • Barcelona, Spain, 08036
  • Barcelona, Spain, 08003
  • Barcelona, Spain, 08035
  • Madrid, Spain, 28040
  • Madrid, Spain, 28041
  • Valencia, Spain, 46014
  • Asturias
    • Oviedo, Asturias, Spain, 33011
• Taiwan
  • Kaohsiung, Taiwan, 833
  • Taichung, Taiwan, 40447
  • Tainan, Taiwan, 736
  • Taipei, Taiwan, 10002
  • Taipei, Taiwan, 106
  • Taoyuan, Taiwan, 33305
• Ukraine
  • Kiev, Ukraine, 115
• United Kingdom
  • Glasgow, United Kingdom, G12 0YN
  • London, United Kingdom, SE1 9RT
  • London, United Kingdom, SW3 6JJ
  • Hampshire
    • Southampton, Hampshire, United Kingdom, SO16 6YD
  • Kent
    • Maidstone, Kent, United Kingdom, ME16 9QQ
  • South Glamorgan
    • Cardiff, South Glamorgan, United Kingdom, CF14 2TL
  • Surrey
    • Sutton, Surrey, United Kingdom, SM2 5PT
• United States
  • California
    • Los Angeles, California, United States, 90025
  • Connecticut
    • New Haven, Connecticut, United States, 06511-5991
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
  • Texas
    • San Antonio, Texas, United States, 78229

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Bayer
• Collaborators: ICON Clinical Research

Publications and helpful links

Helpful Links

• Click here to find information about studies related to Bayer Healthcare products conducted in Europe
• Click here to find results for studies related to Bayer products

Study record dates

Study Major Dates

• Study Start (Actual): December 21, 2007
• Primary Completion (Actual): September 24, 2021
• Study Completion (Actual): September 24, 2021

Study Registration Dates

• First Submitted: February 20, 2008
• First Submitted That Met QC Criteria: February 20, 2008
• First Posted (Estimate): February 28, 2008

Study Record Updates

• Last Update Posted (Actual): September 1, 2022
• Last Update Submitted That Met QC Criteria: August 11, 2022
• Last Verified: August 1, 2022

More Information

Terms related to this study

• Keywords: Cancer; Sorafenib; Extension program
• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Protein Kinase Inhibitors; Sorafenib
• Other Study ID Numbers: 12311; 2007-002604-17 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

IPD Plan Description

Availability of this study's data will later be determined according to Bayer's commitment to the EFPIA/PhRMA "Principles for responsible clinical trial data sharing". This pertains to scope, timepoint and process of data access.

As such, Bayer commits to sharing upon request from qualified researchers patient-level clinical trial data, study-level clinical trial data, and protocols from clinical trials in patients for medicines and indications approved in the US and EU as necessary for conducting legitimate research. This applies to data on new medicines and indications that have been approved by the EU and US regulatory agencies on or after January 01, 2014.

Interested researchers can use www.clinicalstudydatarequest.com to request access to anonymized patient-level data and supporting documents from clinical studies to conduct research. Information on the Bayer criteria for listing studies and other relevant information is provided in the Study sponsors section of the portal.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No