Study Comparing 12 Months Versus 36 Months of Imatinib in the Treatment of Gastrointestinal Stromal Tumor (GIST) - Full Text View

Sponsor:	Scandinavian Sarcoma Group
Information provided by (Responsible Party):	Scandinavian Sarcoma Group
ClinicalTrials.gov Identifier:	NCT00116935

Purpose

In this study, patients who have been diagnosed with gastrointestinal stromal tumor (GIST) will be randomly allocated in a 1:1 ratio to receive imatinib (Gleevec) either for 12 or for 36 months following surgery. The study participants are required to have a histologically verified GIST with a high risk of GIST recurrence despite complete removal of all macroscopic GIST tissue at surgery. The high/very high risk of recurrence is defined as one of the following: 1) the largest tumor diameter is over 10 cm; 2) the mitosis count is high (over 10 mitoses per 50 high power microscope fields, HPFs); 3) the largest tumor diameter over 5 cm and the mitosis count is over 5/50 HPFs; 4) tumor spillage has taken place into the abdominal cavity at the time of surgery or following spontaneous tumor rupture. All study participants will receive imatinib 400 mg/day orally, but the duration of imatinib administration will be determined randomly (either for 12 or for 36 months). The study participants will be followed up using blood tests and computed tomography (or MRI) of the abdomen. The computed tomography examinations will be performed at 6 month intervals for a median of 5 years. A total of 280 patients will be entered into the study. The study hypothesis is that adjuvant imatinib may prevent some of the GIST recurrences, and that there may be a difference in the rate of GIST recurrence between the two groups.

Condition	Intervention	Phase
Sarcoma	Drug: imatinib mesylate Drug: imatinib	Phase III

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Efficacy Study Intervention Model: Parallel Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	Short (12 Months) Versus Long (36 Months) Duration of Adjuvant Treatment With the Tyrosine Kinase Inhibitor Imatinib Mesylate of Operable GIST With a High Risk of Recurrence

Resource links provided by NLM:

Genetics Home Reference related topics: gastrointestinal stromal tumor

MedlinePlus related topics: Cancer Soft Tissue Sarcoma

Drug Information available for: Tyrosine Imatinib Imatinib mesylate

U.S. FDA Resources

Further study details as provided by Scandinavian Sarcoma Group:

Primary Outcome Measures:

Recurrence-free survival [ Time Frame: 5 years ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Adverse effects [ Time Frame: 5 years ] [ Designated as safety issue: Yes ]
Survival [ Time Frame: 5 years ] [ Designated as safety issue: No ]
GIST-specific survival [ Time Frame: 5 years ] [ Designated as safety issue: No ]

Enrollment:	400
Study Start Date:	February 2004
Study Completion Date:	December 2010
Primary Completion Date:	December 2010 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Active Comparator: 1 1 year of adjuvant imatinib mesylate 400 mg/day orally	Drug: imatinib mesylate imatinib 400 mg/day orally qd for 12 months Other Name: Gleevec Drug: imatinib imatinib 400 mg/d orally qd for 36 months Other Name: Gleevec
Experimental: 2 3 years of adjuvant imatinib mesylate 400 mg/day orally	Drug: imatinib imatinib 400 mg/d orally qd for 36 months Other Name: Gleevec

Detailed Description:

This is an open-label, randomized, prospective, phase III, multicenter study carried out in the Nordic countries and in Germany. Following macroscopically complete surgery, the study participants will be allocated to receive imatinib either for 12 or for 36 months. At randomization, the patients are stratified into 2 strata: 1) local disease (1 GIST tumor); 2) intra-abdominal implants or resectable intra-abdominal/hepatic metastases, or intra-abdominal spillage is present, or R1 surgery has been carried out (microscopic disease has been left behind). The imatinib dose is 400 mg/day administered with food. Imatinib dose adjustments are made as per protocol.

Medical history, current medication, weight, height, and ECOG performance status are recorded prior to study entry. Physical examination, blood cell counts, blood biochemistry, pregnancy test, chest X-ray or CT, and CT or MRI of the abdomen and pelvis are carried out/measured prior to study entry. FDG-PET is an optional staging examination. Research serum samples are collected for banking prior to initiating imatinib and at 6-month intervals during the study. Tumor tissue is reviewed centrally to confirm the histological diagnosis of GIST, and KIT and PDGFRA gene mutation analyses will be performed from stored GIST tissue.

The study participants are monitored during adjuvant treatment and following adjuvant treatment. Physical examination, weight and ECOG performance status are assessed at 4- to 26-week intervals. Adverse events are collected using structured forms at the times of the evaluation visits. Blood cell counts and blood biochemistry are measured at 2- to 6-week intervals during imatinib therapy, and at 6-month intervals following completion of adjuvant therapy. CT or MRI examinations of the abdomen and pelvis are performed at 6-month intervals during the study.

Eligibility

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

Criteria

Inclusion Criteria:

Age 18 or older
Histologically documented diagnosis of GIST
Resectable GIST
GIST removed at open surgery
Immunohistochemical documentation of GIST (immunostaining for KIT/CD117)
High risk of tumor recurrence as defined as one of the following: 1) the largest tumor diameter greater than 10.0 cm (measured by a pathologist, with any mitotic count); 2) mitotic count over 10 mitoses per 50 high power fields (HPFs) (with any tumor size); the largest tumor diameter larger than 5.0 cm and the mitotic count is over 5/50 HPFs; 4) tumor spillage into the abdominal cavity at surgery (or tumor rupture). No residual tumors must be present at laparotomy, or in postoperative CT or MRI examinations. Patients who have microscopically infiltrated margins (or suspected microscopical infiltration, R1) are also allowed to enter study.
Performance status 0, 1, or 2 (ECOG)
Adequate organ function, defined as follows: total bilirubin <1.5 x ULN (upper limit of normal), serum AST (SGOT) and ALT (SGPT) <2.5 x ULN, creatinine <1.5 x ULN, ANC (neutrophil count) >1.5 x 10^9/L, platelets >100 x 10^9/L.
Negative pregnancy test (females with childbearing potential)
Written, voluntary informed consent

Exclusion Criteria:

Inoperable or metastatic GIST
Less than 1 week or more than 12 weeks has elapsed from surgery
Recurrent GIST
Patient has received any investigational agents within 28 days as calculated from the first day of the study drug dosing
Patient is less than 5 years free from another primary malignancy
Patient with grade III/IV cardiac problems as defined by the New York Heart Association Criteria
Female patients who are pregnant or breast-feeding
Patient has severe or uncontrolled medical disease (i.e. uncontrolled diabetes, severe chronic renal disease, or active uncontrolled infection). Concurrent use of warfarin or acetaminophen are not allowed with imatinib.
Chronic liver disease
Known diagnosis of human immunodeficiency virus (HIV) infection
Patient has received chemotherapy for GIST
Patient has received neoadjuvant imatinib therapy prior to randomization
Radiotherapy to 25% or more of the bone marrow
Patient with any significant history of non-compliance to medical regimens or with inability to grant reliable informed consent

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00116935

Locations

Sweden
Scandinavian Sarcoma Group, Southern Swedish Regional Tumour Registry, Lund University Hospital
Lund, Sweden, SE-221 85

Sponsors and Collaborators

Scandinavian Sarcoma Group

Investigators

Principal Investigator:

Heikki Joensuu, M.D.

Department of Oncology, Helsinki University Central Hospital

More Information

Additional Information:

Scandinavian Sarcoma Group web site This link exits the ClinicalTrials.gov site

No publications provided

Responsible Party:	Scandinavian Sarcoma Group
ClinicalTrials.gov Identifier:	NCT00116935 History of Changes
Other Study ID Numbers:	SSGXVIII/AIO
Study First Received:	June 30, 2005
Last Updated:	December 28, 2011
Health Authority:	Finland: Finnish Medicines Agency

Keywords provided by Scandinavian Sarcoma Group:

Gastrointestinal stromal tumor
GIST
Sarcoma
Imatinib
Adjuvant therapy

KIT
PDGFRA
Receptor tyrosine kinase
Tyrosine kinase inhibitor

Additional relevant MeSH terms:

Gastrointestinal Stromal Tumors
Sarcoma
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Neoplasms, Connective and Soft Tissue
Neoplasms by Histologic Type

Adjuvants, Immunologic
Imatinib
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on February 09, 2012