A Phase II Uncontrolled Study of BAY73-4506 in Previously Untreated Patients With Metastatic or Unresectable RCC

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Bayer
ClinicalTrials.gov Identifier:
NCT00664326
First received: April 17, 2008
Last updated: May 22, 2014
Last verified: May 2014
  Purpose

This is a uncontrolled, open-label, non-randomized Phase II study of oral BAY73-4506 to evaluate the response rate of BAY73-4506 in previously untreated patients with metastatic or unresectable renal cell cancer (RCC).


Condition Intervention Phase
Carcinoma, Renal Cell
Drug: Regorafenib (Stivarga, BAY73-4506)
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase II Uncontrolled Study of BAY73-4506 in Previously Untreated Patients With Metastatic or Unresectable Renal Cell Cancer (RCC)

Resource links provided by NLM:


Further study details as provided by Bayer:

Primary Outcome Measures:
  • Objective Tumor Response [ Time Frame: From start of treatment of the first participant until database cut-off approximately 13 months later (13May2008 - 31May2009). Assessed every 8 weeks for 6 months, then every 12 weeks ] [ Designated as safety issue: No ]
    Objective tumor response of a participant was defined as the best tumor response (confirmed Complete Response [CR, tumor disappears] or Partial Response [PR, sum of lesion sizes decreased at least 30% from baseline]) observed during trial period assessed according to the Response Evaluation Criteria in Solid Tumors (RECIST) committee.

  • Tumor Response [ Time Frame: From start of treatment of the first participant until database cut-off approximately 13 months later (13May2008 - 31May2009). Assessed every 8 weeks for 6 months, then every 12 weeks ] [ Designated as safety issue: No ]
    Tumor response of a participant was defined as the best tumor response (confirmed Complete Response [CR, tumor disappears], Partial Response [PR, sum of lesion sizes decreased at least 30% from baseline], Stable Disease [SD, steady state of disease], or Progressive Disease [PD, sum of lesion sizes increased at least 20% from smallest sum on study or new lesions]) observed during trial period assessed according to the RECIST committee.


Secondary Outcome Measures:
  • Disease Control [ Time Frame: From start of treatment of the first participant until database cut-off approximately 13 months later (13May2008 - 31May2009). Assessed every 8 weeks for 6 months, then every 12 weeks ] [ Designated as safety issue: No ]
    Disease control was defined as the percentage of participants who had a best response rating of CR (tumor disappears), PR (sum of lesion sizes decreased at least 30% from baseline), or SD (steady state of disease) that was maintained for at least 28 days from the first demonstration of that rating.

  • Overall Survival [ Time Frame: From start of treatment of the first participant until database cut-off approximately 13 months later (13May2008 - 31May2009). ] [ Designated as safety issue: No ]
    Overall survival (OS) was calculated as the time from the first date of receiving study medication to death, due to any cause. Participants alive at the time of analysis were censored at their last date of follow-up.

  • Progression-free Survival (PFS) [ Time Frame: From start of treatment of the first participant until database cut-off approximately 13 months later (13May2008 - 31May2009). Assessed every 8 weeks for 6 months, then every 12 weeks ] [ Designated as safety issue: No ]
    PFS was calculated as time from first date of receiving study drug until date of first observed disease progression (PD) (radiological or clinical, whichever was earlier) or death due to any cause, if death occurred before PD was documented. The actual date of tumor assessments (i.e., date on which radiological procedure was performed, rather than scheduled date) was used for this calculation to determine both the event date and censoring date. Patients without PD or death at time of analysis were censored at last date of tumor evaluation.

  • Time to Progression (TTP) [ Time Frame: From start of treatment of the first participant until database cut-off approximately 13 months later (13May2008 - 31May2009). Assessed every 8 weeks for 6 months, then every 12 weeks ] [ Designated as safety issue: No ]
    TTP was calculated as time from first date of receiving study drug until date of first documented disease progression (PD) (radiological or clinical, whichever was earlier). The actual date of tumor assessments (i.e., date on which radiological procedure was performed, rather than the scheduled date) was used for this calculation to determine both the event date and censoring date. Patients without PD at time of analysis were censored at last date of tumor evaluation.

  • Duration of Response [ Time Frame: From start of treatment of the first participant until database cut-off approximately 13 months later (13May2008 - 31May2009). Assessed every 8 weeks for 6 months, then every 12 weeks ] [ Designated as safety issue: No ]
    Duration of response was defined as the time from the first documented objective response of PR or CR, whichever was earlier, to disease progression or death (if death occurred before progression was documented). Duration of response for subjects who had not progressed or died at the time of analysis were censored at the date of their last tumor assessment.

  • Duration of Stable Disease (SD) [ Time Frame: From start of treatment of the first participant until database cut-off approximately 13 months later (13May2008 - 31May2009). Assessed every 8 weeks for 6 months, then every 12 weeks ] [ Designated as safety issue: No ]
    Duration of SD was calculated as the time from the first date of receiving study drug until the date of documented PD or the last observation if the subject did not progress. Subjects without disease progression at the time of analysis were censored at the last date of tumor evaluation.


Other Outcome Measures:
  • Objective Tumor Response (Update) [ Time Frame: From start of treatment of the first participant until database cut-off approximately 37 months later (13May2008 - 1Jun2011). Assessed every 8 weeks for 6 months, then every 12 weeks ] [ Designated as safety issue: No ]
    Objective tumor response of a participant was defined as the best tumor response (confirmed Complete Response [CR, tumor disappears] or Partial Response [PR, sum of lesion sizes decreased at least 30% from baseline]) observed during trial period assessed according to the RECIST committee.

  • Tumor Response (Update) [ Time Frame: From start of treatment of the first participant until database cut-off approximately 37 months later (13May2008 - 1Jun2011). Assessed every 8 weeks for 6 months, then every 12 weeks ] [ Designated as safety issue: No ]
    Tumor response of a participant was defined as the best tumor response (confirmed Complete Response [CR, tumor disappears], Partial Response [PR, sum of lesion sizes decreased at least 30% from baseline], Stable Disease [SD, steady state of disease], or Progressive Disease [PD, sum of lesion sizes increased at least 20% from smallest sum on study or new lesions]) observed during trial period assessed according to the RECIST committee.

  • Disease Control (Update) [ Time Frame: From start of treatment of the first participant until database cut-off approximately 37 months later (13May2008 - 1Jun2011). Assessed every 8 weeks for 6 months, then every 12 weeks ] [ Designated as safety issue: No ]
    Disease control was defined as the percentage of participants who had a best response rating of CR (tumor disappears), PR (sum of lesion sizes decreased at least 30% from baseline), or SD (steady state of disease) that was maintained for at least 28 days from the first demonstration of that rating.

  • Overall Survival (Update) [ Time Frame: From start of treatment of the first participant until database cut-off approximately 37 months later (13May2008 - 1Jun2011). ] [ Designated as safety issue: No ]
    Overall survival (OS) was calculated as the time from the first date of receiving study medication to death, due to any cause. Participants alive at the time of analysis were censored at their last date of follow-up.

  • Progression-free Survival (Update) [ Time Frame: From start of treatment of the first participant until database cut-off approximately 37 months later (13May2008 - 1Jun2011). Assessed every 8 weeks for 6 months, then every 12 weeks ] [ Designated as safety issue: No ]
    PFS was calculated as time from first date of receiving study drug until date of first observed disease progression (PD) (radiological or clinical, whichever was earlier) or death due to any cause, if death occurred before PD was documented. The actual date of tumor assessments (i.e., date on which radiological procedure was performed, rather than scheduled date) was used for this calculation to determine both the event date and censoring date. Patients without PD or death at time of analysis were censored at last date of tumor evaluation.

  • Time to Progression (Update) [ Time Frame: From start of treatment of the first participant until database cut-off approximately 37 months later (13May2008 - 1Jun2011). Assessed every 8 weeks for 6 months, then every 12 weeks ] [ Designated as safety issue: No ]
    TTP was calculated as time from first date of receiving study drug until date of first documented disease progression (PD) (radiological or clinical, whichever was earlier). The actual date of tumor assessments (i.e., date on which radiological procedure was performed, rather than the scheduled date) was used for this calculation to determine both the event date and censoring date. Patients without PD at time of analysis were censored at last date of tumor evaluation.

  • Duration of Response (Update) [ Time Frame: From start of treatment of the first participant until database cut-off approximately 37 months later (13May2008 - 1Jun2011). Assessed every 8 weeks for 6 months, then every 12 weeks ] [ Designated as safety issue: No ]
    Duration of response was defined as the time from the first documented objective response of PR or CR, whichever was earlier, to disease progression or death (if death occurred before progression was documented). Duration of response for subjects who had not progressed or died at the time of analysis were censored at the date of their last tumor assessment.

  • Duration of Stable Disease (Update) [ Time Frame: From start of treatment of the first participant until database cut-off approximately 37 months later (13May2008 - 1Jun2011). Assessed every 8 weeks for 6 months, then every 12 weeks ] [ Designated as safety issue: No ]
    Duration of SD was calculated as the time from the first date of receiving study drug until the date of documented PD or the last observation if the subject did not progress. Subjects without disease progression at the time of analysis were censored at the last date of tumor evaluation.


Enrollment: 49
Study Start Date: April 2008
Estimated Study Completion Date: December 2014
Primary Completion Date: May 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Regorafenib (Stivarga, BAY73-4506)
Participants received Regorafenib 160 mg per os (po) every day (qd) for 3 weeks on 1 week off of every 4 week cycle
Drug: Regorafenib (Stivarga, BAY73-4506)
Patients will be treated with BAY73-4506 160 mg po qd for 3 weeks of every 4 week cycle (i.e., 3 weeks on, 1 week off). Patients will continue treatment with BAY73-4506 until disease progression, intolerable toxicity, or patient refusal to continue with the study or investigator decision to remove the patient from study.

Detailed Description:

The final analysis of efficacy will be performed after last patient has been treated for at least 6 months. Additional periodic safety and efficacy data reviews will be performed for any patients continuing to receive study drug afterwards.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Male or female patients >/= 18 years of age.
  • Patients, who suffer from unresectable and/or metastatic, measurable predominantly clear cell RCC (renal cell carcinoma histologically) or cytologically documented.
  • Patients must be previously untreated for advanced disease. Prior palliative radiation therapy is allowed if the target lesion(s) are not included within the radiation field and no more than 30% of the bone marrow is irradiated.
  • Patients who have at least one uni-dimensional measurable lesion by computed tomography (CT-scan) or magnetic resonance imaging (MRI) according to Response Evaluation Criteria in Solid Tumors (RECIST).
  • Patients with "Intermediate" or "Low" risk per the Motzer score.
  • Patients who have an Eastern Co-operative Oncology Group (ECOG) performance status of 0 or 1.
  • Adequate bone marrow, renal and hepatic function as assessed by the following laboratory requirements to be conducted within 7 days prior to study drug treatment

Exclusion Criteria:

  • Patients who have received prior systemic treatment regimens for RCC.
  • Uncontrolled/unstable cardiac disease
  • Uncontrolled hypertension
  • Active clinically serious infections (> Common Terminology Criteria for Adverse Events [CTCAE] grade 2 )
  • History of human immunodeficiency virus (HIV) infection or chronic hepatitis B or C.
  • Known history or symptomatic metastatic brain or meningeal tumours
  • Patients with seizure disorder requiring medication
  • Patients with evidence or history of bleeding diathesis. Any hemorrhage or bleeding event >/= CTCAE Grade 3 within 4 weeks of first dose of study.
  • Pregnant or breast-feeding patients
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00664326

Locations
United States, California
Los Angeles, California, United States, 90033
United States, Texas
Houston, Texas, United States, 77030
Finland
Helsinki, Finland, 00029
Turku, Finland, FIN-20521
France
Nantes, France, 44020
Paris, France, 75014
Germany
Frankfurt, Hessen, Germany, 60596
Dresden, Sachsen, Germany, 01307
Berlin, Germany, 10967
Hamburg, Germany, 20246
Poland
Bialystok, Poland, 15-027
Lublin, Poland, 20-090
Poznan, Poland, 60-569
United Kingdom
Bristol, Avon, United Kingdom, BS2 8ED
Leicester, Leicestershire, United Kingdom, LE1 5WW
Cambridge, United Kingdom, CB2 0QQ
London, United Kingdom, SE1 9RT
Northwood, United Kingdom, HA6 2RN
Sponsors and Collaborators
Bayer
Investigators
Study Director: Bayer Study Director Bayer
  More Information

Additional Information:
Publications:
Responsible Party: Bayer
ClinicalTrials.gov Identifier: NCT00664326     History of Changes
Other Study ID Numbers: 11726, 2008-000107-28
Study First Received: April 17, 2008
Results First Received: October 28, 2012
Last Updated: May 22, 2014
Health Authority: United States: Food and Drug Administration
United Kingdom: Medicines and Healthcare Products Regulatory Agency
Germany: Federal Institute for Drugs and Medical Devices
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
Finland: Finnish Medicines Agency
Poland: Ministry of Health

Keywords provided by Bayer:
Renal Cell Carcinoma

Additional relevant MeSH terms:
Carcinoma
Carcinoma, Renal Cell
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Adenocarcinoma
Kidney Neoplasms
Urologic Neoplasms
Urogenital Neoplasms
Neoplasms by Site
Kidney Diseases
Urologic Diseases

ClinicalTrials.gov processed this record on July 24, 2014