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

A Phase II Uncontrolled Study of BAY73-4506 in Previously Untreated Patients With Metastatic or Unresectable Renal Cell Cancer (RCC)

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).

Study Overview

• Status: Completed
• Conditions: Carcinoma, Renal Cell
• Intervention / Treatment: Drug: Regorafenib (Stivarga, BAY73-4506)

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.

• Study Type: Interventional
• Enrollment (Actual): 49
• Phase: Phase 2

Contacts and Locations

Study Locations

• Finland
  • Helsinki, Finland, 00290
  • Turku, Finland, FIN-20521
• France
  • Nantes, France, 44020
  • Paris, France, 75014
• Germany
  • Berlin, Germany, 10967
  • Hamburg, Germany, 20246
  • Hessen
    • Frankfurt, Hessen, Germany, 60596
  • Sachsen
    • Dresden, Sachsen, Germany, 01307
• Poland
  • Bialystok, Poland, 15-027
  • Lublin, Poland, 20-090
  • Poznan, Poland, 60-569
• United Kingdom
  • Bristol, United Kingdom, BS2 8ED
  • Cambridge, United Kingdom, CB2 0QQ
  • London, United Kingdom, SE1 9RT
  • Northwood, United Kingdom, HA6 2RN
  • Leicestershire
    • Leicester, Leicestershire, United Kingdom, LE1 5WW
• United States
  • California
    • Los Angeles, California, United States, 90033
  • Texas
    • Houston, Texas, United States, 77030

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

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: 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Tumor Response	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.	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
Tumor Response	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.	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

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Disease Control	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.	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
Overall Survival	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.	From start of treatment of the first participant until database cut-off approximately 13 months later (13May2008 - 31May2009).
Progression-free Survival (PFS)	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.	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
Time to Progression (TTP)	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.	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
Duration of Response	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.	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
Duration of Stable Disease (SD)	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.	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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Tumor Response (Update)	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.	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
Tumor Response (Update)	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.	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
Disease Control (Update)	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.	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
Overall Survival (Update)	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.	From start of treatment of the first participant until database cut-off approximately 37 months later (13May2008 - 1Jun2011).
Progression-free Survival (Update)	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.	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
Time to Progression (Update)	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.	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
Duration of Response (Update)	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.	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
Duration of Stable Disease (Update)	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.	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

Collaborators and Investigators

• Sponsor: Bayer

Publications and helpful links

General Publications

• Eisen T, Joensuu H, Nathan PD, Harper PG, Wojtukiewicz MZ, Nicholson S, Bahl A, Tomczak P, Pyrhonen S, Fife K, Bono P, Boxall J, Wagner A, Jeffers M, Lin T, Quinn DI. Regorafenib for patients with previously untreated metastatic or unresectable renal-cell carcinoma: a single-group phase 2 trial. Lancet Oncol. 2012 Oct;13(10):1055-62. doi: 10.1016/S1470-2045(12)70364-9. Epub 2012 Sep 6.

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 Healthcare products.

Study record dates

Study Major Dates

• Study Start (Actual): April 30, 2008
• Primary Completion (Actual): May 31, 2009
• Study Completion (Actual): April 2, 2019

Study Registration Dates

• First Submitted: April 17, 2008
• First Submitted That Met QC Criteria: April 17, 2008
• First Posted (Estimate): April 22, 2008

Study Record Updates

• Last Update Posted (Actual): January 29, 2021
• Last Update Submitted That Met QC Criteria: January 27, 2021
• Last Verified: January 1, 2021

More Information

Terms related to this study

• Keywords: Renal Cell Carcinoma
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Kidney Diseases; Urologic Diseases; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Kidney Neoplasms; Carcinoma, Renal Cell
• Other Study ID Numbers: 11726; 2008-000107-28 (EudraCT Number)

Drug and device information, study documents

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