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


Phase 3
18 Years
N/A
Not Enrolling
Both
Sarcoma

Thank you

Trial Information

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


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.


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

Type of Study:

Interventional

Study Design:

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Recurrence-free survival

Outcome Time Frame:

5 years

Safety Issue:

No

Principal Investigator

Heikki Joensuu, M.D.

Investigator Role:

Principal Investigator

Investigator Affiliation:

Department of Oncology, Helsinki University Central Hospital

Authority:

Finland: Finnish Medicines Agency

Study ID:

SSGXVIII/AIO

NCT ID:

NCT00116935

Start Date:

February 2004

Completion Date:

December 2010

Related Keywords:

  • Sarcoma
  • Gastrointestinal stromal tumor
  • GIST
  • Sarcoma
  • Imatinib
  • Adjuvant therapy
  • KIT
  • PDGFRA
  • Receptor tyrosine kinase
  • Tyrosine kinase inhibitor
  • Gastrointestinal Stromal Tumors
  • Sarcoma

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