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

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Bayer
ClinicalTrials.gov Identifier:
NCT01271712
First received: December 17, 2010
Last updated: May 20, 2014
Last verified: May 2014
  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 (Stivarga, BAY73-4506)
Drug: Placebo
Drug: Best supportive care
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:


Further study details as provided by Bayer:

Primary Outcome Measures:
  • Progression-free Survival [ Time Frame: From randomization of the first subject until approximately 144 progression-free survival events had occurred (study duration approximately one year) ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • Overall Survival [ Time Frame: From randomization of the first subject until date of database cutoff (26 Jan 2012); study duration approximately one year ] [ Designated as safety issue: No ]
    Overall Survival (OS) was defined as the time from date of randomization to death due to any cause. Subjects still alive at the time of analysis were censored at their date of last contact. Since the median value could not be estimated due to censored data, the number of participants with events is presented.

  • Time to Progression (TTP) [ Time Frame: From randomization of the first subject until until date of database cutoff (26 Jan 2012); study duration approximately 1 year ] [ Designated as safety issue: No ]
    Time to progression (TTP) was defined as the time from date of randomization to disease progression (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 at the time of analysis were censored at their last date of tumor evaluation. Results are based on central evaluation.

  • Tumor Response [ Time Frame: From randomization of the first subject until date of database cutoff (26 Jan 2012); study duration approximately 1 year ] [ Designated as safety issue: No ]
    Tumor Response of a subject was defined as the best tumor response (Complete Response [CR: disappearance of all clinical and radiological evidence of tumor (both target and non-target).], Partial Response [PR: at least a 30% decrease in the sum of diameters of target lesions taking as reference the baseline sum, no unequivocal progression of existing non-target lesions, and no appearance of new lesions.], Stable Disease [SD: steady state of disease. Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, no unequivocal progression of existing non-target lesions, and no appearance of new lesions.], or Progressive Disease [PD: 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.]) observed during the trial period and assessed according to RECIST v1.1 criteria. Results are based on central evaluation.

  • Objective Response Rate [ Time Frame: From randomization of the first subject until date of database cutoff (26 Jan 2012); study duration approximately 1 year. ] [ Designated as safety issue: No ]
    Objective response rate was defined as the percentage of subjects whose best response was Complete Response (CR: disappearance of all clinical and radiological evidence of tumor (both target and non-target).) or Partial Response (PR: at least a 30% decrease in the sum of diameters of target lesions taking as reference the baseline sum, no unequivocal progression of existing non-target lesions, and no appearance of new lesions.) according to Response Evaluation Criteria in Solid Tumors (RECIST v1.1). Results are based on central evaluation.

  • Disease Control Rate (DCR) [ Time Frame: From randomization of the first subject until date of database cutoff (26 Jan 2012); study duration approximately 1 year ] [ Designated as safety issue: No ]
    Disease Control Rate (DCR) was defined as the percentage of subjects whose best response was Complete Response (CR: disappearance of all clinical and radiological evidence of tumor (both target and non-target).), Partial Response (PR: at least a 30% decrease in the sum of diameters of target lesions taking as reference the baseline sum, no unequivocal progression of existing non-target lesions, and no appearance of new lesions.), or Stable Disease (SD: steady state of disease. Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, no unequivocal progression of existing non-target lesions, and no appearance of new lesions.) according to RECIST v1.1 criteria. SD had to be maintained for at least 12 weeks from the first demonstration of that rating. Results are based on central evaluation.

  • Duration of Response (DOR) [ Time Frame: From randomization of the first subject until date of database cutoff (26 Jan 2012); study duration approximately 1 year ] [ Designated as safety issue: No ]
    Duration of Response was defined as the time from date of first response (Complete Response [CR: disappearance of all clinical and radiological evidence of tumor (both target and non-target).] or Partial Response [PR: at least a 30% decrease in the sum of diameters of target lesions taking as reference the baseline sum, no unequivocal progression of existing non-target lesions, and no appearance of new lesions.]) to the date when Progressive Disease (PD: 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.) is first documented, or to the date of death, whichever occurs first, according to RECIST v1.1. Subjects still having CR or PR and have not died at the time of analysis were censored at their last date of tumor evaluation. Duration of response defined for responders only, i.e CR or PR. Results are based on central evaluation.


Enrollment: 199
Study Start Date: January 2011
Estimated Study Completion Date: June 2016
Primary Completion Date: January 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 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
Drug: Regorafenib (Stivarga, BAY73-4506)
160 mg po once daily (od), 3 weeks on/1 week off. Route of administration: oral
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.
Placebo Comparator: 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
Drug: Placebo
once daily (od), 3 weeks on/1 week off. Route of administration: oral
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.

  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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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:
Publications:
Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Bayer
ClinicalTrials.gov Identifier: NCT01271712     History of Changes
Other Study ID Numbers: 14874, 2009-017957-37
Study First Received: December 17, 2010
Results First Received: May 24, 2013
Last Updated: May 20, 2014
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: 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
Digestive System Diseases
Digestive System Neoplasms
Gastrointestinal Diseases
Gastrointestinal Neoplasms
Neoplasms
Neoplasms by Histologic Type
Neoplasms, Connective and Soft Tissue
Neoplasms, Connective Tissue

ClinicalTrials.gov processed this record on October 20, 2014