NCT00116935

Brief Summary

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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
400

participants targeted

Target at P50-P75 for phase_3

Timeline
Completed

Started Feb 2004

Longer than P75 for phase_3

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

February 1, 2004

Completed
1.4 years until next milestone

First Submitted

Initial submission to the registry

June 30, 2005

Completed
1 day until next milestone

First Posted

Study publicly available on registry

July 1, 2005

Completed
5.4 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

December 1, 2010

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

December 1, 2010

Completed
Last Updated

December 30, 2011

Status Verified

December 1, 2011

Enrollment Period

6.8 years

First QC Date

June 30, 2005

Last Update Submit

December 28, 2011

Conditions

Sarcoma

Keywords

Gastrointestinal stromal tumorGISTSarcomaImatinibAdjuvant therapyKITPDGFRAReceptor tyrosine kinaseTyrosine kinase inhibitor

Outcome Measures

Primary Outcomes (1)

  • Recurrence-free survival

    5 years

Secondary Outcomes (3)

  • Adverse effects

    5 years

  • Survival

    5 years

  • GIST-specific survival

    5 years

Study Arms (2)

1

ACTIVE COMPARATOR

1 year of adjuvant imatinib mesylate 400 mg/day orally

Drug: imatinib mesylateDrug: imatinib

2

EXPERIMENTAL

3 years of adjuvant imatinib mesylate 400 mg/day orally

Drug: imatinib

Interventions

imatinib mesylateDRUG

imatinib 400 mg/day orally qd for 12 months

Also known as: Gleevec
1
imatinibDRUG

imatinib 400 mg/d orally qd for 36 months

Also known as: Gleevec
1

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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

You may not qualify if:

  • 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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Scandinavian Sarcoma Group, Southern Swedish Regional Tumour Registry, Lund University Hospital

Lund, SE-221 85, Sweden

Location

Related Publications (5)

  • Joensuu H, Reichardt A, Eriksson M, Hohenberger P, Boye K, Cameron S, Lindner LH, Jost PJ, Bauer S, Schutte J, Lindskog S, Kallio R, Jaakkola PM, Goplen D, Wardelmann E, Reichardt P. Survival of patients with ruptured gastrointestinal stromal tumour treated with adjuvant imatinib in a randomised trial. Br J Cancer. 2024 Jul;131(2):299-304. doi: 10.1038/s41416-024-02738-z. Epub 2024 Jun 11.

    PMID: 38862742DERIVED

  • Joensuu H, Eriksson M, Sundby Hall K, Reichardt A, Hermes B, Schutte J, Cameron S, Hohenberger P, Jost PJ, Al-Batran SE, Lindner LH, Bauer S, Wardelmann E, Nilsson B, Kallio R, Jaakkola P, Junnila J, Alvegard T, Reichardt P. Survival Outcomes Associated With 3 Years vs 1 Year of Adjuvant Imatinib for Patients With High-Risk Gastrointestinal Stromal Tumors: An Analysis of a Randomized Clinical Trial After 10-Year Follow-up. JAMA Oncol. 2020 Aug 1;6(8):1241-1246. doi: 10.1001/jamaoncol.2020.2091.

    PMID: 32469385DERIVED

  • Joensuu H, Wardelmann E, Sihto H, Eriksson M, Sundby Hall K, Reichardt A, Hartmann JT, Pink D, Cameron S, Hohenberger P, Al-Batran SE, Schlemmer M, Bauer S, Nilsson B, Kallio R, Junnila J, Vehtari A, Reichardt P. Effect of KIT and PDGFRA Mutations on Survival in Patients With Gastrointestinal Stromal Tumors Treated With Adjuvant Imatinib: An Exploratory Analysis of a Randomized Clinical Trial. JAMA Oncol. 2017 May 1;3(5):602-609. doi: 10.1001/jamaoncol.2016.5751.

    PMID: 28334365DERIVED

  • Joensuu H, Eriksson M, Sundby Hall K, Reichardt A, Hartmann JT, Pink D, Ramadori G, Hohenberger P, Al-Batran SE, Schlemmer M, Bauer S, Wardelmann E, Nilsson B, Sihto H, Bono P, Kallio R, Junnila J, Alvegard T, Reichardt P. Adjuvant Imatinib for High-Risk GI Stromal Tumor: Analysis of a Randomized Trial. J Clin Oncol. 2016 Jan 20;34(3):244-50. doi: 10.1200/JCO.2015.62.9170. Epub 2015 Nov 2.

    PMID: 26527782DERIVED

  • Joensuu H, Eriksson M, Sundby Hall K, Hartmann JT, Pink D, Schutte J, Ramadori G, Hohenberger P, Duyster J, Al-Batran SE, Schlemmer M, Bauer S, Wardelmann E, Sarlomo-Rikala M, Nilsson B, Sihto H, Monge OR, Bono P, Kallio R, Vehtari A, Leinonen M, Alvegard T, Reichardt P. One vs three years of adjuvant imatinib for operable gastrointestinal stromal tumor: a randomized trial. JAMA. 2012 Mar 28;307(12):1265-72. doi: 10.1001/jama.2012.347.

    PMID: 22453568DERIVED

Related Links

MeSH Terms

Conditions

SarcomaGastrointestinal Stromal Tumors

Interventions

Imatinib Mesylate

Condition Hierarchy (Ancestors)

Neoplasms, Connective and Soft TissueNeoplasms by Histologic TypeNeoplasmsNeoplasms, Connective TissueGastrointestinal NeoplasmsDigestive System NeoplasmsDigestive System DiseasesGastrointestinal Diseases

Intervention Hierarchy (Ancestors)

BenzamidesAmidesOrganic ChemicalsBenzoatesAcids, CarbocyclicCarboxylic AcidsBenzene DerivativesHydrocarbons, AromaticHydrocarbons, CyclicHydrocarbonsPiperazinesHeterocyclic Compounds, 1-RingHeterocyclic CompoundsPyrimidines

Study Officials

  • Heikki Joensuu, M.D.

    Department of Oncology, Helsinki University Central Hospital

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 3
Allocation
RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

June 30, 2005

First Posted

July 1, 2005

Study Start

February 1, 2004

Primary Completion

December 1, 2010

Study Completion

December 1, 2010

Last Updated

December 30, 2011

Record last verified: 2011-12

Locations

SE(1)