Phase II Study of Regorafenib Continuous Dosing of Regorafenib in Patients With GISTs

NCT02889328 | Completed Phase 2

• 1 other identifier: AMC1602
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 1

Brief Summary

Randomized, placebo-controlled, phase III study of regorafenib 160 mg once daily on intermittent dosing schedule of 3 weeks on treatment followed by 1 weeks off demonstrated the significant benefit of regorafenib in terms of PFS in patients with GISTs who had failed to both imatinib and sunitinib. However, there are concerns that tumors and tumor-related symptoms may be progressed during off treatment period. Investigators hypothesize that continuous dosing schedule of regorafenib might be feasible and effective to prevent disease flare on off-treatment period. Based on the results of previous dose escalation study for continuous regorafenib dosing, we investigate the 100 mg daily dose of regorafenib in patients with TKI-refractory GISTs.

Conditions

Gastrointestinal Stromal Tumors (GISTs)

Outcome Measures

Primary Outcomes (1)

• Disease control rate

  Disease control rate (CR + PR + SD) lasting for at least 12 weeks according to the RECIST v1.1

  at least 12 weeks

Secondary Outcomes (3)

• Progression-free survival

  up to 2 years

• Overall survival

  up to 2 years

• Toxicity profile by the NCI-CTCAE v4.03

  up to 2 years

Study Arms (1)

regorafenib

EXPERIMENTAL

regorafenib 100 mg po od daily, every 4 weeks (28 day)

Drug: Regorafenib

Interventions

Regorafenib DRUG

Regorafenib 100mg continuous dosing arm

regorafenib

Eligibility Criteria

• Age: 20 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age 20 years or older, at the time of acquisition of informed consent
• Histologically confirmed metastatic and/or advanced (unresectable or recurrent) GIST with CD117(+), DOG-1(+), or mutation in KIT or PDGFRα gene
• Disease progression or intolerance to imatinib as well as disease progression on sunitinib Disease progression is defined as (1) size increase \> 20% by RECIST version 1.1, (2) appearance of a definite new lesion (excluding small cystic new lesions in the liver within 6 months of starting TKIs), (3) new solid nodule within a cystic mass, or (4) increase of the size (\> 20%) of previously existing solid nodule within a cystic mass. Intolerance to previous TKIs is defined as (1) drug compliance \< 75% due to grade 2 or more non-hematologic toxicities despite dose reduction to one dose level below (300 mg per day for imatinib; 37.5 mg per day on a 4 weeks on and 2 weeks off schedule or 25 mg per day continuous dosing for sunitinib), (2) Febrile neutropenia, grade 4 neutropenia for more than 6 days, grade 4 thrombocytopenia, grade 3 thrombocytopenia with clinically significant bleeding, grade 3-4 or continuous intolerable grade 2 non-hematologic toxicities despite dose reduction to one dose level below as described above.
• ECOG performance status of 0\~1
• Resolution of all toxic effects of prior treatments to grade 0 or 1 by NCI-CTCAE version 4.03
• At least one measurable lesion as defined by RECIST version 1.1.
• Adequate bone marrow, hepatic, renal, and other organ functions
• Neutrophil \> 1,500/mm3
• Platelet \> 100,000/mm3
• Hemoglobin \> 9.0 g/dL
• Total bilirubin \< 1.5 x upper limit of normal (ULN)
• Lipase ≤ 1.5 x the ULN
• AST/ALT \< 3.0 x ULN (or \< 5 x ULM in case of liver metastases)
• Alkaline phosphatase (ALP) limit ≤ 2.5 x ULN (≤5 x ULN for patients with liver involvement of their cancer and /or have bone metastases).
• Estimated creatinine clearance (CLcr) ≥ 30 mL/min as calculated using the Cockcroft-Gault equation.

You may not qualify if:

• Prior use of any VEGFR inhibitor other than sunitinib (e.g., sorafenib)
• Subjects who have received:
• any other approved tyrosine kinase inhibitor within 1 week or a minimum 5 drug half- lives, whichever is longer (i.e., within 7 days for imatinib or within 10 days for sunitinib)
• any other investigational new drugs within 4 weeks or 5 drug half-lives (if drug half-life in subjects is known), whichever is shorter.
• Women of child-bearing potential who are pregnant or breast feeding or adults of reproductive potential not employing an effective method of birth control.
• Clinically significant cardiac disease (New York Heart Association, Class III or IV) or impaired cardiac function or clinically significant cardiac diseases, including any one of the following:
• LVEF \< 45% as determined by MUGA scan or echocardiogram
• Complete left bundle branch block
• Obligate use of a cardiac pacemaker
• Congenital long QT syndrome
• History or presence of ventricular tachyarrhythmia
• Clinically significant resting bradycardia (\< 50 bpm)
• Uncontrolled hypertension (systolic blood pressure ≥ 150 mmHg and/or diastolic blood pressure ≥ 100 mmHg, with or without anti-hypertensive medication).
• QTc \> 480 msec on screening ECG
• Right bundle branch block + left anterior hemiblock (bifasicular block)

Sponsors & Collaborators

• Asan Medical Center: lead

Study Sites (1)

Asan Medical Center, University of Ulsan College of Medicine

Seoul, 138-736, South Korea

Location

Related Publications (1)

• Kim JJ, Ryu MH, Yoo C, Beck MY, Ma JE, Kang YK. Phase II Trial of Continuous Regorafenib Dosing in Patients with Gastrointestinal Stromal Tumors After Failure of Imatinib and Sunitinib. Oncologist. 2019 Nov;24(11):e1212-e1218. doi: 10.1634/theoncologist.2019-0033. Epub 2019 Apr 29.

  PMID: 31036770 DERIVED

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

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: August 31, 2016
• First Posted: September 5, 2016
• Study Start: September 1, 2016
• Primary Completion: August 9, 2017
• Study Completion: January 1, 2018
• Last Updated: January 9, 2020

Record last verified: 2020-01

Locations

KR (1)