Sorafenib for Imatinib/Sunitinib-failed GIST - Full Text View

Sponsor:	Samsung Medical Center
Collaborator:	Korean GIST Study Group
Information provided by:	Samsung Medical Center
ClinicalTrials.gov Identifier:	NCT01091207

Purpose

With discovery of KIT (CD117) mutations and the advent of KIT tyrosine kinase inhibitor imatinib, there has been substantial improvement in overall survival in patients with advanced and/or metastatic gastrointestinal tumors (GIST). Recently, sunitinib showed activity as second-line therapy in GIST patients after failure with imatinib. However, virtually all patients will eventually progress or become intolerable after imatinib and sunitinib. In preclinical models, sorafenib inhibits KIT activity and cell growth of imatinib-resistant tumors. The objective of this multi-center, non-randomized phase II study is to evaluate the safety and activity of sorafenib given as third-line therapy for GIST.

Condition	Intervention	Phase
Gastrointestinal Stromal Tumors	Drug: Sorafenib	Phase II

Study Type:	Interventional
Study Design:	Allocation: Non-Randomized Endpoint Classification: Efficacy Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	A Phase II Study of Sorafenib in Patients With Metastatic or Advanced Gastrointestinal Stromal Tumors Who Failed to Imatinib and Sunitinib

Resource links provided by NLM:

Genetics Home Reference related topics: gastrointestinal stromal tumor

MedlinePlus related topics: Cancer

Drug Information available for: Imatinib Imatinib mesylate Sorafenib Sunitinib malate Sorafenib tosylate Sunitinib

U.S. FDA Resources

Further study details as provided by Samsung Medical Center:

Primary Outcome Measures:

Disease-control rate [ Time Frame: Six months after registration ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Response rate [ Time Frame: Every 2 months ] [ Designated as safety issue: No ]

Estimated Enrollment:	39
Study Start Date:	November 2009
Study Completion Date:	August 2011
Primary Completion Date:	December 2010 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Sorafenib The patients will receive daily oral administration of sorafenib 400 mg twice daily.	Drug: Sorafenib The patients will receive daily oral administration of sorafenib 400 mg twice daily.

Detailed Description:

This is a non-randomized, open-label, multi-center, phase II study recruiting patients with advanced GIST who are pretreated with both imatinib and sunitinib. The current study will provide an estimate of the activity and safety of sorafenib in GIST. The primary study endpoint is the disease control rate (DCR), defined as complete or partial response or stable disease of at least 24 weeks of sorafenib therapy. Secondary endpoints include PFS, OS and safety.

Patients with advanced (unresectable and/or metastatic) GIST who failed after previous therapy involving both imatinib and sunitinib will be eligible. Failure to imatinib and sunitinib is defined as disease progression regardless of intervening response during therapy, or intolerance. There is no limit to the number of prior therapies a patient may have received (e.g., patients may have received therapy with nilotinib, other TKIs, or chemotherapy in addition to imatinib or sunitinib).

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

age over 18 years
advanced GIST
failed (progressed and/or intolerable) after prior treatments for GIST
ECOG performance status of 0~2
resolution of all toxic effects of prior treatments
no prior radiotherapy within 1 month before registration
measurable lesion as defined by RECIST
adequate marrow, hepatic, renal and cardiac functions
provision of a signed written informed consent

Exclusion Criteria:

severe co-morbid illness and/or active infections
pregnant or lactating women
history of other malignancies
active CNS disease not controllable with radiotherapy or corticosteroids
active and uncontrollable bleeding from gastrointestinal tract
prior history of sorafenib use
gastrointestinal obstruction or malabsorption syndrome

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT01091207

Locations

Korea, Republic of
Samsung Medical Center
Seoul, Korea, Republic of, 135710

Sponsors and Collaborators

Samsung Medical Center

Korean GIST Study Group

Investigators

Principal Investigator:

Se Hoon Park, MD

Samsung Medical Center, Seoul, Korea

More Information

No publications provided

Responsible Party:	Se Hoon Park, Samsung Medical Center, Seoul, Korea
ClinicalTrials.gov Identifier:	NCT01091207 History of Changes
Other Study ID Numbers:	2009-08-102
Study First Received:	November 30, 2009
Last Updated:	January 18, 2012
Health Authority:	South Korea: Korea Food and Drug Administration (KFDA)

Keywords provided by Samsung Medical Center:

Sorafenib
GIST
Refractory
advanced GIST failed after both imatinib and sunitinib

Additional relevant MeSH terms:

Gastrointestinal Stromal Tumors
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Imatinib
Sorafenib
Sunitinib
Antineoplastic Agents

Therapeutic Uses
Pharmacologic Actions
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Physiological Effects of Drugs
Growth Inhibitors

ClinicalTrials.gov processed this record on February 09, 2012