Study of Regorafenib as a 3rd-line or Greater Treatment for Gastrointestinal Stromal Tumors (GIST) - Full Text View

Sponsor:	Bayer
Information provided by:	Bayer
ClinicalTrials.gov Identifier:	NCT01271712

Purpose

A randomized, double-blind, placebo-controlled phase III study of regorafenib plus best supportive care versus placebo plus best supportive care for subjects with metastatic and/or unresectable gastrointestinal stromal tumors (GIST) whose disease has progressed despite prior treatment with at least imatinib and sunitinib.

The study is composed of 3 periods: A Screening Period, a Treatment Period, and a Survival Follow up Period.

Subjects randomized to be treated with regorafenib will receive 160 mg po od for 3 weeks of every 4 week (28 day) cycle (ie, 3 weeks on/1 week off). In addition subjects will receive best supportive care which excludes any disease specific anti cancer therapy such as any kinase inhibitor, chemotherapy, radiation therapy, or surgery.

Tumor assessment will be every 4 weeks for the first 3 months, every 6 weeks for the next 3 months (through month 6), and every 8 weeks until the end of treatment, or more frequently if clinically indicated. Tumor assessments include CT or MRI and will be performed until tumor progression is seen in a central radiology review.

Subjects receiving placebo who experience disease progression may be offered active treatment.

Subjects who experience progression during regorafenib treatment may continue open label treatment.

All subjects will enter the Survival Follow-up Period upon discontinuation of randomized study treatment.

Condition	Intervention	Phase
Gastrointestinal Stromal Tumors	Drug: Regorafenib (BAY 73-4506) Drug: Placebo	Phase 3

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor) Primary Purpose: Treatment
Official Title:	A Randomized, Double-blind, Placebo-controlled Phase III Study of Regorafenib Plus Best Supportive Care Versus Placebo Plus Best Supportive Care for Subjects With Metastatic and/or Unresectable Gastrointestinal Stromal Tumors (GIST) Whose Disease Has Progressed Despite Prior Treatment With at Least Imatinib and Sunitinib

Resource links provided by NLM:

MedlinePlus related topics: Cancer

U.S. FDA Resources

Further study details as provided by Bayer:

Primary Outcome Measures:

Progression-Free Survival (PFS), per blinded central radiology review. [ Time Frame: approx.12 months after FPFT (after approx. 144 PFS events have been observed) ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Overall Survival (OS) [ Time Frame: approx.12 months after FPFT (after approx. 144 PFS events have been observed) after approx. 136 OS events have been observed ] [ Designated as safety issue: No ]
Time to Progression (TTP) [ Time Frame: approx.12 months after FPFT (after approx. 144 PFS events have been observed) ] [ Designated as safety issue: No ]
Disease Control Rate (DCR) [ Time Frame: approx.12 months after FPFT (after approx. 144 PFS events have been observed) ] [ Designated as safety issue: No ]
Tumor Response Rate (RR) [ Time Frame: approx.12 months after FPFT (after approx. 144 PFS events have been observed) ] [ Designated as safety issue: No ]
Duration of Response (DOR) [ Time Frame: approx.12 months after FPFT (after approx. 144 PFS events have been observed) ] [ Designated as safety issue: No ]

Enrollment:	199
Study Start Date:	January 2011
Estimated Study Completion Date:	January 2013
Primary Completion Date:	January 2012 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Arm 1	Drug: Regorafenib (BAY 73-4506) 160 mg po once daily (od), 3 weeks on/1 week off. Route of administration: oral
Placebo Comparator: Arm 2	Drug: Placebo once daily (od), 3 weeks on/1 week off. Route of administration: oral

Eligibility

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

Criteria

Inclusion Criteria:

Male or female subjects 18 years of age.
Subjects with histologically confirmed metastatic and/or unresectable GIST.
At least imatinib and sunitinib as prior treatment regimens, with objective disease progression or intolerance to imatinib, as well as disease progression while on sunitinib therapy. Additionally, disease progression or intolerance to other systemic therapies, as well as investigational new agents, is allowed, except prior treatment with any other vascular endothelial growth factor receptor (VEGFR) inhibitor.
Subjects must have at least one measurable lesion according to Response Evaluation Criteria in Solid Tumors (RECIST), version 1.1. A lesion in a previously irradiated area is eligible to be considered as measurable disease as long as there is objective evidence of progression of the lesion prior to study enrollment.

Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1.

Adequate bone marrow, liver, and renal function as assessed by laboratory parameters.

Recovery to NCI-CTCAE v4.0 Grade 0 or 1 level or recovery to baseline preceding the prior treatment from any previous drug/procedure-related toxicity (except alopecia and anemia).

Exclusion Criteria:

Major surgical procedure, open biopsy, or significant traumatic injury within 28 days before start of study medication.
Congestive heart failure New York Heart Association (NYHA) class 2.
Unstable angina (angina symptoms at rest, new-onset angina, ie, within the last 3 months) or myocardial infarction (MI) within the past 6 months before start of study medication.
Uncontrolled hypertension (systolic blood pressure 140 mmHg or diastolic pressure 90 mmHg despite optimal medical management).

Arterial thrombotic or embolic events such as cerebrovascular accident (including transient ischemic attacks), or pulmonary embolism within the 6 months before start of study drug or venous thrombotic events such as deep vein thrombosis within the 3 months before start of study drug.

Ongoing infection grade 2 National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.0.

Symptomatic metastatic brain or meningeal tumors.

Subjects with evidence or history of bleeding diathesis. Any hemorrhage or bleeding event NCI-CTCAE version 4.0 grade 3 or higher within 4 weeks prior to the start of study drug.

Non-healing wound, ulcer, or bone fracture.

Persistent proteinuria of NCI-CTCAE version 4.0 grade 3 or higher (3.5 g/24 hrs, measured by urine protein:creatinine ratio on a random urine sample).

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT01271712

Show 89 Study Locations

Sponsors and Collaborators

Bayer

Investigators

Study Director:

Bayer Study Director

Bayer

More Information

Additional Information:

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No publications provided

Responsible Party:	Therapeutic Area Head, Bayer Health Care AG
ClinicalTrials.gov Identifier:	NCT01271712 History of Changes
Other Study ID Numbers:	14874, 2009-017957-37
Study First Received:	December 17, 2010
Last Updated:	May 3, 2012
Health Authority:	United States: Food and Drug Administration Austria:AGES-PharmMed LCM Belgium:Agence Fédérale des Médicaments et des Produits de Santé Canada: Health Canada China: State Food and Drug Administration Finland: Finnish Medicines Agency France: Agence française de sécurité sanitaire des produits de santé (Afssaps) Germany: Federal Institute for Drugs and Medical Devices Israel: Ministry of Health Italy: Agenzia Italiana del Farmaco Japan: Pharmaceuticals and Medical Devices Agency Netherlands: College ter Beoordeling van Geneesmiddelen Medicines Evaluation Board Poland: Office for Registration of Medicinal Products, Medical Devices and Biocidal Products Singapore: Health Sciences Authority South Korea: Korea Food and Drug Administration Spain: Agencia Española de Medicamentos y Productos Sanitarios United Kingdom: Medicines and Healthcare Products Regulatory Agency

Keywords provided by Bayer:

Gastrointestinal stromal cancer
GIST
multikinase inhibitor

Additional relevant MeSH terms:

Gastrointestinal Stromal Tumors
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site

Neoplasms
Digestive System Diseases
Gastrointestinal Diseases

ClinicalTrials.gov processed this record on May 23, 2012