Study of Regorafenib as a 3rd-line or Beyond Treatment for Gastrointestinal Stromal Tumors (GIST)

NCT ID: NCT01271712

Last Updated: 2021-01-29

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 199 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-01-04
• Study Completion Date: 2019-04-15

Brief Summary

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.

Conditions

Gastrointestinal Stromal Tumors

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Regorafenib (Stivarga, BAY73-4506)

Participants received Regorafenib (Stivarga) 160 mg (4 x 40 mg tablets) per os once daily, 3 weeks on therapy followed by 1 week off therapy to comprise a cycle of 4 weeks

Group Type: EXPERIMENTAL

Regorafenib (Stivarga, BAY73-4506)

Intervention Type: DRUG

160 mg po once daily (od), 3 weeks on/1 week off. Route of administration: oral

Best supportive care

Intervention Type: DRUG

Best supportive care includes any method to preserve the comfort and dignity of the patients, and excludes any disease-specific anti-neoplastic therapy such as any kinase inhibitor, chemotherapy, radiation therapy, or surgical intervention.

Placebo

Participants received matching Placebo tablets per os once daily, 3 weeks on therapy followed by 1 week off therapy to comprise a cycle of 4 weeks

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

once daily (od), 3 weeks on/1 week off. Route of administration: oral

Best supportive care

Intervention Type: DRUG

Best supportive care includes any method to preserve the comfort and dignity of the patients, and excludes any disease-specific anti-neoplastic therapy such as any kinase inhibitor, chemotherapy, radiation therapy, or surgical intervention.

Interventions

Regorafenib (Stivarga, BAY73-4506)

160 mg po once daily (od), 3 weeks on/1 week off. Route of administration: oral

Intervention Type: DRUG

Placebo

once daily (od), 3 weeks on/1 week off. Route of administration: oral

Intervention Type: DRUG

Best supportive care

Best supportive care includes any method to preserve the comfort and dignity of the patients, and excludes any disease-specific anti-neoplastic therapy such as any kinase inhibitor, chemotherapy, radiation therapy, or surgical intervention.

Intervention Type: DRUG

Eligibility 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).

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Bayer

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Bayer Study Director

Role: STUDY_DIRECTOR

Bayer

Locations

Scottsdale, Arizona, United States

Evanston, Illinois, United States

Skokie, Illinois, United States

Boston, Massachusetts, United States

Minneapolis, Minnesota, United States

New York, New York, United States

Portland, Oregon, United States

Philadelphia, Pennsylvania, United States

Seattle, Washington, United States

Graz, Styria, Austria

Innsbruck, , Austria

Vienna, , Austria

Leuven, , Belgium

Edmonton, Alberta, Canada

London, Ontario, Canada

Toronto, Ontario, Canada

Guangzhou, Guangdong, China

Nanjing, Jiangsu, China

Beijing, , China

Shanghai, , China

Helsinki, , Finland

Bordeaux, , France

Lille, , France

Lyon, , France

Villejuif, , France

Mannheim, Baden-Wurttemberg, Germany

Tübingen, Baden-Wurttemberg, Germany

Bad Saarow, Brandenburg, Germany

Hanover, Lower Saxony, Germany

Cologne, North Rhine-Westphalia, Germany

Düsseldorf, North Rhine-Westphalia, Germany

Essen, North Rhine-Westphalia, Germany

Tel Aviv, , Israel

Bologna, Emilia-Romagna, Italy

Milan, Lombardy, Italy

Turin, Piedmont, Italy

Palermo, Sicily, Italy

Nagoya, Aichi-ken, Japan

Kashiwa, Chiba, Japan

Sapporo, Hokkaido, Japan

Chuo-ku, Tokyo, Japan

Niigata, , Japan

Osaka, , Japan

Leiden, , Netherlands

Nijmegen, , Netherlands

Warsaw, , Poland

Singapore, , Singapore

Goyang-si, Gyeonggido, South Korea

Busan, , South Korea

Seoul, , South Korea

Seoul, , South Korea

Seoul, , South Korea

L'Hospitalet de Llobregat, Barcelona, Spain

Barcelona, , Spain

Leicester, Leicestershire, United Kingdom

London, , United Kingdom

Manchester, , United Kingdom

Countries

United States; Austria; Belgium; Canada; China; Finland; France; Germany; Israel; Italy; Japan; Netherlands; Poland; Singapore; South Korea; Spain; United Kingdom

References

Demetri GD, Reichardt P, Kang YK, Blay JY, Rutkowski P, Gelderblom H, Hohenberger P, Leahy M, von Mehren M, Joensuu H, Badalamenti G, Blackstein M, Le Cesne A, Schoffski P, Maki RG, Bauer S, Nguyen BB, Xu J, Nishida T, Chung J, Kappeler C, Kuss I, Laurent D, Casali PG; GRID study investigators. Efficacy and safety of regorafenib for advanced gastrointestinal stromal tumours after failure of imatinib and sunitinib (GRID): an international, multicentre, randomised, placebo-controlled, phase 3 trial. Lancet. 2013 Jan 26;381(9863):295-302. doi: 10.1016/S0140-6736(12)61857-1. Epub 2012 Nov 22.

Reference Type: RESULT

PMID: 23177515 (View on PubMed)

Poole CD, Connolly MP, Chang J, Currie CJ. Health utility of patients with advanced gastrointestinal stromal tumors (GIST) after failure of imatinib and sunitinib: findings from GRID, a randomized, double-blind, placebo-controlled phase III study of regorafenib versus placebo. Gastric Cancer. 2015 Jul;18(3):627-34. doi: 10.1007/s10120-014-0391-x. Epub 2014 Jun 24.

Reference Type: RESULT

PMID: 24957256 (View on PubMed)

Komatsu Y, Doi T, Sawaki A, Kanda T, Yamada Y, Kuss I, Demetri GD, Nishida T. Regorafenib for advanced gastrointestinal stromal tumors following imatinib and sunitinib treatment: a subgroup analysis evaluating Japanese patients in the phase III GRID trial. Int J Clin Oncol. 2015 Oct;20(5):905-12. doi: 10.1007/s10147-015-0790-y. Epub 2015 Feb 6.

Reference Type: RESULT

PMID: 25655899 (View on PubMed)

Mross K, Frost A, Steinbild S, Hedbom S, Buchert M, Fasol U, Unger C, Kratzschmar J, Heinig R, Boix O, Christensen O. A phase I dose-escalation study of regorafenib (BAY 73-4506), an inhibitor of oncogenic, angiogenic, and stromal kinases, in patients with advanced solid tumors. Clin Cancer Res. 2012 May 1;18(9):2658-67. doi: 10.1158/1078-0432.CCR-11-1900. Epub 2012 Mar 15.

Reference Type: DERIVED

PMID: 22421192 (View on PubMed)

Related Links

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Other Identifiers

2009-017957-37

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

14874

Identifier Type: -

Identifier Source: org_study_id