Trial Condition(s):

Gastrointestinal stromal tumors

Study of regorafenib as a 3rd-line or beyond treatment for gastrointestinal stromal tumors (GIST) (GRID)

Bayer Identifier:

14874

ClinicalTrials.gov Identifier:

NCT01271712

EudraCT Number:

2009-017957-37

Study Completed

Trial 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.

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).

Trial Summary

Enrollment Goal
199
Trial Dates
black-arrow
Phase
3
Could I receive a placebo?
Yes
Products
Stivarga (Regorafenib, BAY73-4506)
Accepts Healthy Volunteers
No

Where to Participate

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Locations
Status
LocationsStatus
Locations

Investigative Site

Bad Saarow, Germany, 15526

Status
Completed
 
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Investigative Site

Köln, Germany, 50924

Status
Completed
 
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Investigative Site

Essen, Germany, 45122

Status
Completed
 
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Mannheim, Germany, 68167

Status
Completed
 
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Investigative Site

Seoul, South Korea, 138-736

Status
Completed
 
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Busan, South Korea, 49201

Status
Completed
 
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Tel Aviv, Israel, 64239

Status
Completed
 
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Shanghai, China, 200030

Status
Completed
 
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Singapore, Singapore, 169610

Status
Completed
 
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LEUVEN, Belgium, 3000

Status
Completed
 
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Graz, Austria, 8036

Status
Completed
 
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Wien, Austria, 1090

Status
Completed
 
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Innsbruck, Austria, 6020

Status
Completed
 
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Seoul, South Korea, 03080

Status
Completed
 
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Seoul, South Korea, 06351

Status
Completed
 
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Goyang-si, South Korea, 410-769

Status
Completed
 
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Hannover, Germany, 30625

Status
Completed
 
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Tübingen, Germany, 72076

Status
Completed
 
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Leiden, Netherlands, 2333 ZA

Status
Completed
 
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Helsinki, Finland, 00290

Status
Completed
 
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Lyon Cedex 08, France, 69373

Status
Completed
 
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Bordeaux Cedex, France, 33076

Status
Completed
 
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LILLE CEDEX, France, 59020

Status
Completed
 
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Milano, Italy, 20133

Status
Completed
 
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Torino, Italy, 10060

Status
Completed
 
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Bologna, Italy, 40138

Status
Completed
 
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Warszawa, Poland, 02-781

Status
Completed
 
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London, United Kingdom, SW3 6JJ

Status
Completed
 
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Toronto, Canada, M5G 1X5

Status
Completed
 
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Boston, United States, 02115

Status
Completed
 
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New York, United States, 10065

Status
Completed
 
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Portland, United States, 97239-2964

Status
Completed
 
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Philadelphia, United States, 19111-2497

Status
Completed
 
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Seattle, United States, 98109

Status
Completed
 
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Evanston, United States, 60201

Status
Completed
 
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Skokie, United States, 60076

Status
Completed
 
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Minneapolis, United States, 55455

Status
Completed
 
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Nanjing, China, 210002

Status
Completed
 
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Guangzhou, China, 510060

Status
Completed
 
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Manchester, United Kingdom, M20 4BX

Status
Completed
 
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Kashiwa, Japan, 277-8577

Status
Completed
 
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Niigata, Japan, 951-8520

Status
Completed
 
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Osaka, Japan, 543-0035

Status
Completed
 
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Chuo-ku, Japan, 104-0045

Status
Completed
 
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Edmonton, Canada, T6G 1Z2

Status
Completed
 
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London, Canada, N6A 4L6

Status
Completed
 
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Leicester, United Kingdom, LE1 5WW

Status
Completed
 
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Sapporo, Japan, 060-8648

Status
Completed
 
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Barcelona, Spain, 08035

Status
Completed
 
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L'Hospitalet de Llobregat, Spain, 08907

Status
Completed
 
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Nagoya, Japan, 466-8650

Status
Completed
 
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Palermo, Italy, 90127

Status
Completed
 
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Düsseldorf, Germany, 40479

Status
Completed
 
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VILLEJUIF, France, 94805

Status
Completed
 
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NIJMEGEN, Netherlands, 6525 GA

Status
Completed
 
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Investigative Site

Scottsdale, United States, 85258

Status
Completed
 
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Investigative Site

Beijing, China, 100071

Status
Completed
 

Trial Design