Comparison of Nexavar/Placebo as Maintenance Therapy for Patients With Advanced Ovarian or Primary Peritoneal Cancer

A Double-Blind, Randomized Phase II Study Evaluating the Efficacy and Safety of Sorafenib Compared to Placebo in Ovarian Epithelial Cancer or Primary Peritoneal Cancer Patients Who Have Achieved a Complete Clinical Response After Standard Platinum/Taxane Containing Chemotherapy

Comparison of Nexavar with a placebo as maintenance therapy for patients with advanced Ovarian or primary Peritoneal cancers in complete remission following surgery and one regimen of chemotherapy.

Study Overview

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

• Study Type: Interventional
• Enrollment (Actual): 246
• Phase: Phase 2

Contacts and Locations

Study Locations

• Belgium
  • Bruxelles - Brussel, Belgium, 1200
  • Bruxelles - Brussel, Belgium, 1000
  • Edegem, Belgium, 2650
  • La Louviere, Belgium, 7100
  • Leuven, Belgium, 3000
  • Wilrijk, Belgium, 2610
• Canada
  • Ontario
    • Hamilton, Ontario, Canada, L8V 5C2
    • London, Ontario, Canada, N6A 4L6
    • Toronto, Ontario, Canada, M5G 2M9
  • Quebec
    • Montreal, Quebec, Canada, H2L 4M1
• Finland
  • Jyväskylä, Finland, FI-40620
  • Kuopio, Finland, FIN- 70211
• France
  • ANGERS cedex 9, France, 49933
  • Caen Cedex 5, France, 14076
  • Lyon Cedex, France, 39373
  • Tours, France, 37044
  • Villejuif, France, 94805
• Germany
  • Berlin, Germany, 13353
• Hong Kong
  • Hong Kong, Hong Kong
  • HongKong, Hong Kong
• Italy
  • Campobasso, Italy, 00168
  • Milano, Italy, 20141
  • Roma, Italy, 00168
  • Roma, Italy, 00167
  • Forlì
    • Meldola, Forlì, Italy, 47014
• Japan
  • Aichi
    • Nagoya, Aichi, Japan, 464-8681
  • Chiba
    • Kashiwa, Chiba, Japan, 277-8567
  • Kanagawa
    • Isehara, Kanagawa, Japan, 259-1193
  • Tochigi
    • Shimotsuke, Tochigi, Japan, 329-0498
  • Tokyo
    • Koto-ku, Tokyo, Japan, 135-8550
    • Minato-ku, Tokyo, Japan, 105-8471
• Korea, Republic of
  • Daegu, Korea, Republic of, 700-712
  • Gyeonggi-do, Korea, Republic of, 410-769
  • Incheon, Korea, Republic of, 405-760
  • Seoul, Korea, Republic of, 158-710
  • Seoul, Korea, Republic of, 138-736
  • Seoul, Korea, Republic of, 120-752
  • Seoul, Korea, Republic of, 135-710
  • Sowon, Korea, Republic of, 443-721
  • Seoul Teugbyeolsi
    • Seoul, Seoul Teugbyeolsi, Korea, Republic of, 110-744
• Netherlands
  • Den Haag, Netherlands, 2545 CH
  • Maastricht, Netherlands, 6229 HX
• Poland
  • Bialystok, Poland, 15-027
  • Gdynia, Poland, 81-519
  • Krakow, Poland, 31-115
  • Lublin, Poland
  • Poznan, Poland, 61-866
  • Poznan, Poland, 61-878
  • Warszawa, Poland, 02-781
• Singapore
  • Singapore, Singapore, 119228
  • Singapore, Singapore, 229899
• Spain
  • Lugo, Spain, 27003
  • Madrid, Spain, 28040
  • Madrid, Spain, 28041
  • Sevilla, Spain, 41013
  • Barcelona
    • Sabadell, Barcelona, Spain, 08208
• United States
  • California
    • La Jolla, California, United States, 92037
  • Florida
    • Jacksonville, Florida, United States, 32209
  • Georgia
    • Augusta, Georgia, United States, 30912
  • Maine
    • Scarborough, Maine, United States, 04074

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:

• Histologically confirmed International Federation of Gynecology and Obstetrics (FIGO) stage (67) III or IV ovarian epithelial cancer or primary peritoneal cancer at presentation. Patients must have achieved a clinical complete response (disappearance of all clinical and radiological evidence of tumor) after only one regimen (4-6 cycles) of platinum and taxane-based standard chemotherapy received after tumor debulkment.
• Normal serum CA125 (cancer-associated tumor marker) level within 7 days of first dose of sorafenib.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• All scans used to document complete response must be done within 30 days prior to randomization.
• Patients must be able to swallow and retain oral medication.

Exclusion Criteria:

• Patients with any residual cancer tissue after the completion of chemotherapy detectable by standard Computed tomography (CT) or magnetic resonance imaging (MRI).
• Prior local radiotherapy, neoadjuvant chemotherapy or intraperitoneal chemotherapy.
• Histologic subtypes of ovarian cancer other than epithelial (i.e. sarcoma, lymphoma, germ cell).
• Major surgery, open biopsy, or significant traumatic injury within 30 days prior to randomization.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Sorafenib (Nexavar, BAY43-9006); Participants received 2 sorafenib tablets (200 mg each) per oral twice daily (bid)	Drug: Sorafenib (Nexavar, BAY43-9006); Patients in Sorafenib arm will receive 2 Sorafenib tablets (200 mg each) twice a day and in continuous administration.
Placebo Comparator: Placebo; Participants received 2 matching placebo tablets per oral twice daily	Drug: Placebo; Patients in Placebo arm will receive 2 matching placebo tablets twice a day and in continuous administration.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-free Survival (PFS), Based on Radiological or Pathologic Assessment	Time from randomization to the first documented disease progression by radiological or pathologic assessment or death due to any cause whichever occurred first. For patients who had not progressed or died at the time of analysis, PFS was censored at the date of their last evaluable tumor scan.	From randomization of the first patient until 32.5 months later, assessed every 8 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to First Pathologic CA-125 (Cancer-associated Tumor Marker) Serum Level	Time from randomization to the first documented increase of CA-125 above the upper limit of normal. Patients without pathologic CA-125 increase at the time of analysis were censored at their last date of evaluation of CA-125.	From randomization of the first patient until 32.5 months later, assessed every 8 weeks
Overall Survival (OS)	The OS time was measured from the date of randomization until the date of death due to any cause. Patients who were alive at the time of analysis were censored at the date of the last contact (last time the patient was known to be alive).	From randomization of the first patient until 32.5 months later

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Functional Assessment of Cancer Therapy (FACT)/National Comprehensive Cancer Network (NCCN) Ovarian Symptom Index (FOSI) Total Score at Cycle 1/Baseline	The FOSI is an 8-item index derived from the FACT-Ovarian Cancer (FACT-O) to measure symptom response to treatment for ovarian cancer. The FOSI total score ranges from 0 (severely symptomatic) to 32 (asymptomatic).	At Cycle 1 (4 weeks per Cycle)/baseline
FOSI Total Score at Cycle 3	The FOSI is an 8-item index derived from the FACT-Ovarian Cancer (FACT-O) to measure symptom response to treatment for ovarian cancer. The FOSI total score ranges from 0 (severely symptomatic) to 32 (asymptomatic).	At Cycle 3 (4 weeks per Cycle)
Change From Baseline in FOSI Total Score at Cycle 3	The FOSI is an 8-item index derived from the FACT-Ovarian Cancer (FACT-O) to measure symptom response to treatment for ovarian cancer. The change is calculated as score at Cycle 3 minus baseline score. The change in FOSI total score ranges from -32 (most deterioration from baseline) to 32 (most improvement from baseline).	Baseline and Cycle 3 (4 weeks per Cycle)
FOSI Total Score at Cycle 5	The FOSI is an 8-item index derived from the FACT-Ovarian Cancer (FACT-O) to measure symptom response to treatment for ovarian cancer. The FOSI total score ranges from 0 (severely symptomatic) to 32 (asymptomatic).	At Cycle 5 (4 weeks per Cycle)
Change From Baseline in FOSI Total Score at Cycle 5	The FOSI is an 8-item index derived from the FACT-Ovarian Cancer (FACT-O) to measure symptom response to treatment for ovarian cancer. The change is calculated as score at Cycle 5 minus baseline score. The change in FOSI total score ranges from -32 (most deterioration from baseline) to 32 (most improvement from baseline).	Baseline and Cycle 5 (4 weeks per Cycle)
FOSI Total Score at End of Treatment	The FOSI is an 8-item index derived from the FACT-Ovarian Cancer (FACT-O) to measure symptom response to treatment for ovarian cancer. The FOSI total score ranges from 0 (severely symptomatic) to 32 (asymptomatic).	At End of treatment (up to Cycle 33, 4 weeks per Cycle)
Change From Baseline in FOSI Total Score at End of Treatment	The FOSI is an 8-item index derived from the FACT-Ovarian Cancer (FACT-O) to measure symptom response to treatment for ovarian cancer. The change is calculated as score at End of treatment minus baseline score. The change in FOSI total score ranges from -32 (most deterioration from baseline) to 32 (most improvement from baseline).	Baseline and End of treatment (up to Cycle 33, 4 weeks per Cycle)
EuroQol-5D (EQ-5D) Index Score at Cycle 1/Baseline	The EQ-5D contains a descriptive system which measures 5 health dimensions: mobility, self-care, usual activity, pain/discomfort, and anxiety/depression. These five health dimensions are summarized into a single score, the EQ-5D index score which ranges from -0.594 (worst) to 1 (best) when the United Kingdom (UK) weights are applied.	At Cycle 1 (4 weeks per Cycle)/baseline
EQ-5D Index Score at Cycle 3	The EQ-5D contains a descriptive system which measures 5 health dimensions: mobility, self-care, usual activity, pain/discomfort, and anxiety/depression. These five health dimensions are summarized into a single score, the EQ-5D index score which ranges from -0.594 (worst) to 1 (best) when the United Kingdom (UK) weights are applied.	At Cycle 3 (4 weeks per Cycle)
Change From Baseline in EQ-5D Index Score at Cycle 3	The EQ-5D contains a descriptive system which measures 5 health dimensions: mobility, self-care, usual activity, pain/discomfort, and anxiety/depression. These five health dimensions are summarized into a single score, the EQ-5D index. The change is calculated as score at Cycle 3 minus baseline score. The change in EQ-5D index ranges from -1.594 (most deterioration from baseline) to 1.594 (most improvement from baseline).	Baseline and Cycle 3 (4 weeks per Cycle)
EQ-5D Index Score at Cycle 5	The EQ-5D contains a descriptive system which measures 5 health dimensions: mobility, self-care, usual activity, pain/discomfort, and anxiety/depression. These five health dimensions are summarized into a single score, the EQ-5D index score which ranges from -0.594 (worst) to 1 (best) when the United Kingdom (UK) weights are applied.	At Cycle 5 (4 weeks per Cycle)
Change From Baseline in EQ-5D Index Score at Cycle 5	The EQ-5D contains a descriptive system which measures 5 health dimensions: mobility, self-care, usual activity, pain/discomfort, and anxiety/depression. These five health dimensions are summarized into a single score, the EQ-5D index. The change is calculated as score at Cycle 5 minus baseline score. The change in EQ-5D index ranges from -1.594 (most deterioration from baseline) to 1.594 (most improvement from baseline).	Baseline and Cycle 5 (4 weeks per Cycle)
EQ-5D Index Score at End of Treatment	The EQ-5D contains a descriptive system which measures 5 health dimensions: mobility, self-care, usual activity, pain/discomfort, and anxiety/depression. These five health dimensions are summarized into a single score, the EQ-5D index score which ranges from -0.594 (worst) to 1 (best) when the United Kingdom (UK) weights are applied.	At End of treatment (up to Cycle 33, 4 weeks per Cycle)
Change From Baseline in EQ-5D Index Score at End of Treatment	The EQ-5D contains a descriptive system which measures 5 health dimensions: mobility, self-care, usual activity, pain/discomfort, and anxiety/depression. These five health dimensions are summarized into a single score, the EQ-5D index. The change is calculated as score at End of treatment minus baseline score. The change in EQ-5D index ranges from -1.594 (most deterioration from baseline) to 1.594 (most improvement from baseline).	Baseline and End of treatment (up to Cycle 33, 4 weeks per Cycle)
EQ-5D Visual Analogue Scale (VAS) Score at Cycle 1/Baseline	The EQ-5D also contains a VAS, which records the respondent's self-rated health status on a vertical graduated scale. The scale ranges from 0 (worst imaginable health state) to 100 (best imaginable health state).	At Cycle 1 (4 weeks per Cycle)/baseline
EQ-5D VAS Score at Cycle 3	The EQ-5D also contains a VAS, which records the respondent's self-rated health status on a vertical graduated scale. The scale ranges from 0 (worst imaginable health state) to 100 (best imaginable health state).	At Cycle 3 (4 weeks per Cycle)
Change From Baseline in EQ-5D VAS Score at Cycle 3	The EQ-5D also contains a VAS, which records the respondent's self-rated health status on a vertical graduated scale. The change is calculated as score at Cycle 3 minus baseline score. The change in EQ-5D VAS ranges from -100 (most deterioration from baseline) to 100 (most improvement from baseline).	Baseline and Cycle 3 (4 weeks per Cycle)
EQ-5D VAS Score at Cycle 5	The EQ-5D also contains a VAS, which records the respondent's self-rated health status on a vertical graduated scale. The scale ranges from 0 (worst imaginable health state) to 100 (best imaginable health state).	At Cycle 5 (4 weeks per Cycle)
Change From Baseline in EQ-5D VAS Score at Cycle 5	The EQ-5D also contains a VAS, which records the respondent's self-rated health status on a vertical graduated scale. The change is calculated as score at Cycle 5 minus baseline score. The change in EQ-5D VAS ranges from -100 (most deterioration from baseline) to 100 (most improvement from baseline).	Baseline and Cycle 5 (4 weeks per Cycle)
EQ-5D VAS Score at End of Treatment	The EQ-5D also contains a VAS, which records the respondent's self-rated health status on a vertical graduated scale. The scale ranges from 0 (worst imaginable health state) to 100 (best imaginable health state).	At End of treatment (up to Cycle 33, 4 weeks per Cycle)
Change From Baseline in EQ-5D VAS Score at End of Treatment	The EQ-5D also contains a VAS, which records the respondent's self-rated health status on a vertical graduated scale. The change is calculated as score at End of treatment minus baseline score. The change in EQ-5D VAS ranges from -100 (most deterioration from baseline) to 100 (most improvement from baseline).	Baseline and End of treatment (up to Cycle 33, 4 weeks per Cycle)

Collaborators and Investigators

• Sponsor: Bayer

Publications and helpful links

General Publications

• Herzog TJ, Scambia G, Kim BG, Lhomme C, Markowska J, Ray-Coquard I, Sehouli J, Colombo N, Shan M, Petrenciuc O, Oza A. A randomized phase II trial of maintenance therapy with Sorafenib in front-line ovarian carcinoma. Gynecol Oncol. 2013 Jul;130(1):25-30. doi: 10.1016/j.ygyno.2013.04.011. Epub 2013 Apr 13.

Helpful Links

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

Study record dates

Study Major Dates

• Study Start: November 1, 2008
• Primary Completion (Actual): July 1, 2011
• Study Completion (Actual): December 1, 2012

Study Registration Dates

• First Submitted: November 14, 2008
• First Submitted That Met QC Criteria: November 14, 2008
• First Posted (Estimate): November 17, 2008

Study Record Updates

• Last Update Posted (Estimate): September 28, 2015
• Last Update Submitted That Met QC Criteria: August 26, 2015
• Last Verified: June 1, 2015

More Information

Terms related to this study

• Keywords: Peritoneal Neoplasma
• Additional Relevant MeSH Terms: Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Genital Neoplasms, Female; Endocrine System Diseases; Ovarian Diseases; Adnexal Diseases; Gonadal Disorders; Endocrine Gland Neoplasms; Ovarian Neoplasms; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Protein Kinase Inhibitors; Sorafenib
• Other Study ID Numbers: 12007 (DAIDS-ES Registry Number); 2008-004429-41 (EudraCT Number)