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

NCT01271712 | Completed Phase 3 Results DMC FDA Drug

• 2 other identifiers: 148742009-017957-37
• Study Type: interventional
• Target: 199
• Locations: 17 countries
• Sites: 57

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

Keywords

Gastrointestinal stromal cancer; GIST; multikinase inhibitor

Outcome Measures

Primary Outcomes (1)

• Progression-free Survival

  Progression-free Survival (PFS) was defined as the time from date of randomization to radiological disease progression or death due to any cause, whichever occurs first. PFS was based on central radiological assessment using modified RECIST (Response Evaluation Criteria in Solid Tumors) v.1.1. Progression is defined as at least a 20% increase in the sum of diameters of target lesions taking as reference the smallest sum on study; or unequivocal progression of existing non-target lesions; or appearance of new lesions. Subjects without progression or death at the time of analysis were censored at their last date of tumor evaluation. Results are based on central evaluation.

  From randomization of the first subject until approximately 144 progression-free survival events had occurred (study duration approximately one year)

Secondary Outcomes (6)

• Overall Survival

  From randomization of the first subject until date of database cutoff (08 Jun 2015)

• Time to Progression (TTP)

  From randomization of the first subject until until date of database cutoff (26 Jan 2012); study duration approximately 1 year

• Tumor Response

  From randomization of the first subject until date of database cutoff (26 Jan 2012); study duration approximately 1 year

• Objective Response Rate

  From randomization of the first subject until date of database cutoff (26 Jan 2012); study duration approximately 1 year.

• Disease Control Rate (DCR)

  From randomization of the first subject until date of database cutoff (26 Jan 2012); study duration approximately 1 year

Study Arms (2)

Regorafenib (Stivarga, BAY73-4506)

EXPERIMENTAL

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

Drug: Regorafenib (Stivarga, BAY73-4506); Drug: Best supportive care

Placebo

PLACEBO COMPARATOR

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

Drug: Placebo; Drug: Best supportive care

Interventions

Regorafenib (Stivarga, BAY73-4506) DRUG

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

Regorafenib (Stivarga, BAY73-4506)

Placebo DRUG

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

Placebo

Best supportive care 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; Regorafenib (Stivarga, BAY73-4506)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).

You may not qualify if:

• 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).

Sponsors & Collaborators

• Bayer: lead

Study Sites (57)

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Scottsdale, Arizona, 85258, United States

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Evanston, Illinois, 60201, United States

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Skokie, Illinois, 60076, United States

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Boston, Massachusetts, 02115, United States

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Minneapolis, Minnesota, 55455, United States

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New York, New York, 10065, United States

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Portland, Oregon, 97239-2964, United States

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Philadelphia, Pennsylvania, 19111-2497, United States

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Seattle, Washington, 98109, United States

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Graz, Styria, 8036, Austria

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Innsbruck, 6020, Austria

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Vienna, 1090, Austria

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Leuven, 3000, Belgium

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Edmonton, Alberta, T6G 1Z2, Canada

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London, Ontario, N6A 4L6, Canada

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Toronto, Ontario, M5G 1X5, Canada

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Guangzhou, Guangdong, 510060, China

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Nanjing, Jiangsu, 210002, China

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Beijing, 100071, China

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Shanghai, 200030, China

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Helsinki, 00290, Finland

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Bordeaux, 33076, France

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Lille, 59020, France

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Lyon, 69373, France

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Villejuif, 94805, France

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Mannheim, Baden-Wurttemberg, 68167, Germany

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Tübingen, Baden-Wurttemberg, 72076, Germany

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Bad Saarow, Brandenburg, 15526, Germany

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Hanover, Lower Saxony, 30625, Germany

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Cologne, North Rhine-Westphalia, 50924, Germany

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Düsseldorf, North Rhine-Westphalia, 40479, Germany

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Essen, North Rhine-Westphalia, 45122, Germany

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Tel Aviv, 64239, Israel

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Bologna, Emilia-Romagna, 40138, Italy

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Milan, Lombardy, 20133, Italy

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Turin, Piedmont, 10060, Italy

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Palermo, Sicily, 90127, Italy

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Nagoya, Aichi-ken, 466-8650, Japan

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Kashiwa, Chiba, 277-8577, Japan

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Sapporo, Hokkaido, 060-8648, Japan

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Chuo-ku, Tokyo, 104-0045, Japan

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Niigata, 951-8520, Japan

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Osaka, 543-0035, Japan

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Leiden, 2333 ZA, Netherlands

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Nijmegen, 6525 GA, Netherlands

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Warsaw, 02-781, Poland

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Singapore, 169610, Singapore

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Goyang-si, Gyeonggido, 410-769, South Korea

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Busan, 49201, South Korea

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Seoul, 03080, South Korea

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Seoul, 06351, South Korea

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Seoul, 138-736, South Korea

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L'Hospitalet de Llobregat, Barcelona, 08907, Spain

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Barcelona, 08035, Spain

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Leicester, Leicestershire, LE1 5WW, United Kingdom

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London, SW3 6JJ, United Kingdom

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Manchester, M20 4BX, United Kingdom

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Related Publications (4)

• 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.

  PMID: 23177515 RESULT

• 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.

  PMID: 24957256 RESULT

• 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.

  PMID: 25655899 RESULT

• 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.

  PMID: 22421192 DERIVED

Related Links

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

MeSH Terms

Conditions

Gastrointestinal Stromal Tumors

Interventions

regorafenib

Condition Hierarchy (Ancestors)

Neoplasms, Connective Tissue; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases

Limitations and Caveats

Overall survival results are confounded by the fact that 85% of the participants initially randomized to placebo switched to open-label regorafenib.

Results Point of Contact

• Title: Therapeutic Area Head
• Organization: BAYER

clinical-trials-contact@bayer.com

Study Officials

• Bayer Study Director

  Bayer

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: GT60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 17, 2010
• First Posted: January 7, 2011
• Study Start: January 4, 2011
• Primary Completion: January 26, 2012
• Study Completion: April 15, 2019
• Last Updated: January 29, 2021
• Results First Posted: October 25, 2013

Record last verified: 2021-01

Locations

PL (1); FI (1); IT (4); SG (1); GB (3); CN (4); CA (3); NL (2); FR (4); US (9); BE (1); IL (1); JP (6); ES (2); AU (3); DE (7); KR (5)