Overview

This trial is active, not recruiting.

Condition gastrointestinal stromal tumors
Treatments regorafenib (stivarga, bay73-4506), placebo, best supportive care
Phase phase 3
Sponsor Bayer
Start date January 2011
End date January 2012
Trial size 199 participants
Trial identifier NCT01271712, 14874, 2009-017957-37

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.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation randomized
Endpoint classification safety/efficacy study
Intervention model parallel assignment
Masking double blind (subject, caregiver, investigator, outcomes assessor)
Primary purpose treatment
Arm
(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
regorafenib (stivarga, bay73-4506)
160 mg po once daily (od), 3 weeks on/1 week off. Route of administration: oral
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)
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
placebo
once daily (od), 3 weeks on/1 week off. Route of administration: oral
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.

Primary Outcomes

Measure
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)

Secondary Outcomes

Measure
Overall Survival
time frame: From randomization of the first subject until date of database cutoff (26 Jan 2012); study duration approximately one year
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
Tumor Response
time frame: From randomization of the first subject until date of database cutoff (26 Jan 2012); study duration approximately 1 year
Objective Response Rate
time frame: From randomization of the first subject until date of database cutoff (26 Jan 2012); study duration approximately 1 year.
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
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

Eligibility Criteria

Male or female participants at least 18 years old.

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).

Additional Information

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
Trial information was received from ClinicalTrials.gov and was last updated in December 2015.
Information provided to ClinicalTrials.gov by Bayer.