Five Year Adjuvant Imatinib Mesylate (Gleevec®) in Gastrointestinal Stromal Tumor (GIST)

Sponsor
Novartis Pharmaceuticals (Industry)
Overall Status
Completed
CT.gov ID
NCT00867113
Collaborator
(none)
91
Enrollment
21
Locations
1
Arm
89
Actual Duration (Months)
4.3
Patients Per Site
0
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This is a Phase II, non-randomized, open-label, multi-center study conducted in the USA. The purpose of this trial is to evaluate the use of long term adjuvant imatinib mesylate in patients at significant risk for recurrence following complete resection of primary GIST.

Condition or DiseaseIntervention/TreatmentPhase
  • Drug: imatinib mesylate
Phase 2

Detailed Description

This is a Phase II, non-randomized, open-label, multi-center study conducted in the USA. The primary endpoint is to evaluate the use of long term adjuvant imatinib mesylate in patients at significant risk for recurrence following complete resection of primary GIST. A total of 85 adult patients, 18 years of age and older will be enrolled.Participants will take 400 mg of imatinib mesylate daily by mouth for a total of 5 years. At the conclusion of the treatment period, patients will be followed for 2 years for survival, status of response and antineoplastic treatments and quality of life.

Study Design

Study Type:
Interventional
Actual Enrollment :
91 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Phase II, Non-Randomized, Open-Label Multicenter Study of 5 Year Adjuvant Imatinib Mesylate (Gleevec®) in Patients at Significant Risk for Recurrence Following Complete Resection of Primary Gastrointestinal Stromal Tumor (GIST)
Actual Study Start Date :
Jul 22, 2009
Actual Primary Completion Date :
Dec 20, 2016
Actual Study Completion Date :
Dec 20, 2016

Arms and Interventions

ArmIntervention/Treatment
Experimental: Imatinib

All subjects received in tablet form imatinib (STI571) 400 mg once daily.

Drug: imatinib mesylate
imatinib mesylate was supplied in 100 and 400 mg tablets

Outcome Measures

Primary Outcome Measures

  1. Recurrence-free Survival up to 60 Months [Baseline up to 60 months]

    Recurrence-free survival assessment is based on the radiologic evidence and is defined as the time from the date of first dose of imatinib to the date of the first documented disease recurrence or death due to any cause (event).

  2. Kaplan-Meier Estimates for Recurrence-free Survival up to 60 Months [Baseline up to 60 months]

    Recurrence-free survival (RFS) assessment is based on the radiologic evidence and is defined as the time from the date of first dose of imatinib to the date of the first documented disease recurrence or death due to any cause (event). RFS estimates were summarized using the Kaplan-Meier product-limit method (Kaplan 1958). Censoring rules for RFS with the earliest occurring rule used in the analysis: subjects without objective recurrence of disease who were alive at the time of their discontinuation from study were censored at the end of study date or end of treatment visit date if the subject refused to be followed post treatment and subjects recording antineoplastic therapy during the study were censored on the date of the therapy initiated

Secondary Outcome Measures

  1. Overall Survival (OS) at 60 Months [Baseline up to approximately 60 months]

    Overall survival was defined as the time from the date of the first dose of study drug to the date of death. Subjects who were alive at the time of discontinuation/completion of the study were censored at the end of study date or end of treatment visit date if the subject refused to be followed post treatment. Full analysis set.

  2. Kaplan-Meier Estimates for Overall Survival (OS) up to 60 Months [Baseline up to appoximately 60 months]

    Overall survival was defined as the time from the date of the first dose of study drug to the date of death. Subjects who were alive at the time of discontinuation/completion of the study were censored at the end of study date or end of treatment visit date if the subject refused to be followed post treatment. Full analysis set.

Eligibility Criteria

Criteria

Ages Eligible for Study:
18 Years and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:
  1. Patients 18 years of age or older.

  2. Patient must have had a histological diagnosis of primary GIST.

  3. The tumor must expressed KIT (CD117) protein by immunohistochemistry performed by central pathology.

  4. Patient must have been at significant risk of tumor recurrence as defined by either:

  • Primary GIST (any site): ≥ 2 cm and a mitotic rate of ≥ 5/50 HPF's

  • Non-gastric primary GIST: ≥ 5cm

  1. Patient must have undergone complete gross resection of a primary GIST within 12 weeks prior to first dose of imatinib study drug. The inclusion of R1 resections will be reviewed on a case by case basis by the Study Management Committee.

  2. Patient must had no evidence of metastatic GIST on either 1) a post-operative CT of the abdomen and pelvis with intravenous and oral contrast or 2) MRI of the abdomen and pelvis with intravenous contrast. CT or MRI must have been performed within 8 weeks prior to first dose of imatinib study drug.

  3. Performance status 0 or 1 (ECOG)

  4. Patient must had the following post-operative laboratory values confirmed within 14 days prior to first dose of imatinib study drug:

  • total bilirubin < 1.5 x ULN NOTE: Patients with elevated bilirubin secondary to Gilbert's disease are eligible to participate in the study.

  • ALT and AST < 2.5 x ULN

  • creatinine < 1.5 x ULN

  • ANC > 1.5 x 109/L

  • platelets > 100 x 109/L

  1. If patient is a cancer survivor, ALL of the following criteria apply:
  • Patient had undergone potentially curative therapy for all prior malignancies.

  • No evidence of any prior malignancies for at least 3 years with no evidence of recurrence (except for effectively treated basal cell or squamous carcinoma of the skin, carcinoma in-situ of the cervix that has been effectively treated by surgery alone, or lobular carcinoma in-situ of the ipsilateral or contralateral breast treated by surgery alone).

  • Patient is deemed by their treating physician to be at low risk for recurrence from prior malignancies.

  1. Female patients of childbearing potential must have had negative pregnancy test within 7 days before initiation of study drug dosing. Postmenopausal women must have been amenorrheic for at least 12 months to be considered of non-childbearing potential. Female patients of reproductive potential must have jagreed to employ an effective barrier method of birth control throughout the study and for up to 7 days following discontinuation of study drug.

  2. Written, voluntary informed consent.

Exclusion Criteria:
  1. Patient has metastatic GIST to the peritoneum, liver, lymph node, or other sites or recurrent GIST.

  2. Prior treatment for GIST with the exception of prior treatment with imatinib adjuvant lasting ≤ 8 weeks following gross surgical resection.

  3. Patient has received any other investigational agents within 28 days of first day of study drug dosing.

  4. Patient with Grade III/IV cardiac problems as defined by the New York Heart Association Criteria. (i.e., congestive heart failure, myocardial infarction within 6 months of study)

  5. Patients with severe and/or uncontrolled concurrent medical disease that in the opinion of the investigator could cause unacceptable safety risk or compromise compliance with the protocol (i.e., uncontrolled diabetes, chronic renal disease, chronic liver disease, or active uncontrolled infection).

  6. Patient has a known diagnosis of human immunodeficiency virus (HIV) infection.

  7. Patient receiving concurrent treatment with warfarin (acceptable alternative: low-molecular weight heparin).

  8. Patient with any significant history of non-compliance to medical regimens or with inability to grant reliable informed consent.

Contacts and Locations

Locations

SiteCityStateCountryPostal Code
1University of California San Diego - Moores Cancer Center Moores UCSD Cancer Center (31)La JollaCaliforniaUnited States92093-0658
2University of Colorado University of ColoradoAuroraColoradoUnited States80045
3Washington Hospital Center Department of Medical OncologyWashingtonDistrict of ColumbiaUnited States20010
4University Cancer & Blood Center, LLCAthensGeorgiaUnited States30607
5Longstreet Cancer CenterGainesvilleGeorgiaUnited States30501
6Kootenai Medical Center Kootenai Cancer CancerCoeur d'AleneIdahoUnited States83814
7North Shore University Health SystemEvanstonIllinoisUnited States60201
8Dana Farber Cancer Institute Dana-FarberBostonMassachusettsUnited States02215
9Karmanos Cancer Institute Karmonos Cancer Instit. (40)DetroitMichiganUnited States48201
10Washington University School of Medicine Center for Advanced MedicineSaint LouisMissouriUnited States63110
11Southern Nevada Cancer Research Foundation S. Nevada Cancer Res (2)Las VegasNevadaUnited States89106
12Dartmouth Hitchcock Medical CenterLebanonNew HampshireUnited States03756
13Memorial Sloan Kettering Cancer Center Memorial Sloan Kettering (7)New YorkNew YorkUnited States10021
14Duke University Medical Center Duke University Med Ctr (8)DurhamNorth CarolinaUnited States27710
15Oregon Health & Science University OHS UniversityPortlandOregonUnited States97239
16Penn State University / Milton S. Hershey Medical Center Penn Stat UniversityHersheyPennsylvaniaUnited States17033-0850
17Roger Williams Medical Center Medical CenterProvidenceRhode IslandUnited States02908
18Kingport Hematology OncologyKingsportTennesseeUnited States37660
19MD Anderson Cancer Center/University of Texas MD Anderson Cancer Center (4)HoustonTexasUnited States77030
20South Texas Oncology and Hematology, PA South Texas Onc/HemSan AntonioTexasUnited States78259
21Virginia Oncology Associates Viriginia Oncology Assoc.NorfolkVirginiaUnited States23502

Sponsors and Collaborators

  • Novartis Pharmaceuticals

Investigators

  • Study Director: Novartis Pharmaceuticals, Novartis Pharmaceuticals

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

Publications

None provided.
Responsible Party:
Novartis Pharmaceuticals
ClinicalTrials.gov Identifier:
NCT00867113
Other Study ID Numbers:
  • CSTI571BUS282
First Posted:
Mar 23, 2009
Last Update Posted:
Mar 14, 2018
Last Verified:
Mar 1, 2018

Study Results

Participant Flow

Recruitment Details
Pre-assignment DetailTotal of 113 subjects were screened and 91 were enrolled..
Arm/Group TitleImatinib
Arm/Group DescriptionAll subjects received in tablet form imatinib (STI571) 400 mg once daily.
Period Title: Treatment Period
STARTED91
Safety Set91
Full Analysis Set (FAS)91
COMPLETED46
NOT COMPLETED45
Period Title: Treatment Period
STARTED68
COMPLETED57
NOT COMPLETED11

Baseline Characteristics

Arm/Group TitleImatinib
Arm/Group DescriptionAll subjects received in tablet form imatinib (STI571) 400 mg once daily.
Overall Participants91
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]
58.9
(12.64)
Sex: Female, Male (Count of Participants)
Female
43
47.3%
Male
48
52.7%
ECOG Status (Count of Participants)
ECOG = 0
59
64.8%
ECOG = 1
32
35.2%
Primary lesion location (participant) [Number]
Gastric
50
Duodenum
4
Jejunum ileum
21
Rectum
1
Other
15
Abdomen
1
Abdominal; Proximal Jejunal
1
Exact Location In Small Bowel Not Identified
1
Gastric Serosa-Min Invasion Outer Musc Prop
1
Ileum And Cecum
1
Pelvis - Organ Of Origin Unknown
1
Recto Vaginal
1
Retroperitoneal Mass
1
Sigmoid Colon
1
Small Bowel
6

Outcome Measures

1. Primary Outcome
TitleRecurrence-free Survival up to 60 Months
DescriptionRecurrence-free survival assessment is based on the radiologic evidence and is defined as the time from the date of first dose of imatinib to the date of the first documented disease recurrence or death due to any cause (event).
Time FrameBaseline up to 60 months

Outcome Measure Data

Analysis Population Description
[Not Specified]
Arm/Group TitleImatinib
Arm/Group DescriptionAll subjects received in tablet form imatinib (STI571) 400 mg once daily.
Measure Participants91
Subject with an event
9
9.9%
Event = disease recurrence
7
7.7%
Event=death
2
2.2%
Subjects censored
82
90.1%
2. Primary Outcome
TitleKaplan-Meier Estimates for Recurrence-free Survival up to 60 Months
DescriptionRecurrence-free survival (RFS) assessment is based on the radiologic evidence and is defined as the time from the date of first dose of imatinib to the date of the first documented disease recurrence or death due to any cause (event). RFS estimates were summarized using the Kaplan-Meier product-limit method (Kaplan 1958). Censoring rules for RFS with the earliest occurring rule used in the analysis: subjects without objective recurrence of disease who were alive at the time of their discontinuation from study were censored at the end of study date or end of treatment visit date if the subject refused to be followed post treatment and subjects recording antineoplastic therapy during the study were censored on the date of the therapy initiated
Time FrameBaseline up to 60 months

Outcome Measure Data

Analysis Population Description
[Not Specified]
Arm/Group TitleImatinib
Arm/Group DescriptionAll subjects received in tablet form imatinib (STI571) 400 mg once daily.
Measure Participants91
12 months
97.7
18 months
97.7
24 months
96.5
36 months
95.1
48 months
95.1
60 months
90.1
3. Secondary Outcome
TitleOverall Survival (OS) at 60 Months
DescriptionOverall survival was defined as the time from the date of the first dose of study drug to the date of death. Subjects who were alive at the time of discontinuation/completion of the study were censored at the end of study date or end of treatment visit date if the subject refused to be followed post treatment. Full analysis set.
Time FrameBaseline up to approximately 60 months

Outcome Measure Data

Analysis Population Description
[Not Specified]
Arm/Group TitleImatinib
Arm/Group DescriptionAll subjects received in tablet form imatinib (STI571) 400 mg once daily.
Measure Participants91
subjects who died
3
3.3%
subjects censored
88
96.7%
4. Secondary Outcome
TitleKaplan-Meier Estimates for Overall Survival (OS) up to 60 Months
DescriptionOverall survival was defined as the time from the date of the first dose of study drug to the date of death. Subjects who were alive at the time of discontinuation/completion of the study were censored at the end of study date or end of treatment visit date if the subject refused to be followed post treatment. Full analysis set.
Time FrameBaseline up to appoximately 60 months

Outcome Measure Data

Analysis Population Description
[Not Specified]
Arm/Group TitleImatinib
Arm/Group DescriptionAll subjects received in tablet form imatinib (STI571) 400 mg once daily.
Measure Participants91
12 months
100.00
109.9%
18 months
100.00
109.9%
24 months
98.0
107.7%
36 months
98.0
107.7%
48 months
98.0
107.7%
60 months
93.8
103.1%

Adverse Events

Time FrameAdverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit up to approximately 7 years
Adverse Event Reporting Description
Arm/Group TitleImatinib
Arm/Group DescriptionImatinib
All Cause Mortality
Imatinib
Affected / at Risk (%)# Events
Total/ (NaN)
Serious Adverse Events
Imatinib
Affected / at Risk (%)# Events
Total28/91 (30.8%)
Blood and lymphatic system disorders
ANAEMIA4/91 (4.4%)
LEUKOCYTOSIS1/91 (1.1%)
Cardiac disorders
CARDIAC FAILURE1/91 (1.1%)
CARDIAC FAILURE CHRONIC1/91 (1.1%)
CORONARY ARTERY DISEASE1/91 (1.1%)
MITRAL VALVE INCOMPETENCE1/91 (1.1%)
Gastrointestinal disorders
ABDOMINAL ADHESIONS1/91 (1.1%)
ABDOMINAL PAIN2/91 (2.2%)
COLITIS1/91 (1.1%)
DIARRHOEA1/91 (1.1%)
GASTRIC ULCER1/91 (1.1%)
GASTROINTESTINAL HAEMORRHAGE1/91 (1.1%)
HAEMORRHOIDAL HAEMORRHAGE1/91 (1.1%)
HAEMORRHOIDS1/91 (1.1%)
NAUSEA2/91 (2.2%)
PANCREATITIS1/91 (1.1%)
RECTAL HAEMORRHAGE1/91 (1.1%)
RETCHING1/91 (1.1%)
SMALL INTESTINAL OBSTRUCTION3/91 (3.3%)
SMALL INTESTINAL PERFORATION1/91 (1.1%)
VOMITING2/91 (2.2%)
General disorders
CHEST PAIN1/91 (1.1%)
MALAISE2/91 (2.2%)
PAIN1/91 (1.1%)
Hepatobiliary disorders
CHOLELITHIASIS1/91 (1.1%)
Immune system disorders
HYPERSENSITIVITY1/91 (1.1%)
Infections and infestations
ABDOMINAL INFECTION1/91 (1.1%)
APPENDICITIS1/91 (1.1%)
APPENDICITIS PERFORATED1/91 (1.1%)
CELLULITIS1/91 (1.1%)
GASTROENTERITIS1/91 (1.1%)
PERITONITIS2/91 (2.2%)
PNEUMONIA4/91 (4.4%)
SIALOADENITIS1/91 (1.1%)
Injury, poisoning and procedural complications
FALL1/91 (1.1%)
HIP FRACTURE2/91 (2.2%)
HUMERUS FRACTURE1/91 (1.1%)
OVERDOSE1/91 (1.1%)
Investigations
HEPATIC ENZYME INCREASED1/91 (1.1%)
LIPASE INCREASED1/91 (1.1%)
WEIGHT DECREASED1/91 (1.1%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
DESMOID TUMOUR1/91 (1.1%)
HAIR FOLLICLE TUMOUR BENIGN1/91 (1.1%)
NEOPLASM MALIGNANT1/91 (1.1%)
PROSTATE CANCER3/91 (3.3%)
UTERINE LEIOMYOMA1/91 (1.1%)
Nervous system disorders
CEREBROVASCULAR ACCIDENT2/91 (2.2%)
RADICULOPATHY1/91 (1.1%)
TRANSIENT ISCHAEMIC ATTACK1/91 (1.1%)
Psychiatric disorders
CONFUSIONAL STATE1/91 (1.1%)
DELIRIUM1/91 (1.1%)
DEPRESSION1/91 (1.1%)
Renal and urinary disorders
ACUTE KIDNEY INJURY1/91 (1.1%)
RENAL MASS1/91 (1.1%)
URETERIC STENOSIS1/91 (1.1%)
Respiratory, thoracic and mediastinal disorders
ALVEOLITIS1/91 (1.1%)
PLEURAL EFFUSION1/91 (1.1%)
Vascular disorders
HYPERTENSION2/91 (2.2%)
Other (Not Including Serious) Adverse Events
Imatinib
Affected / at Risk (%)# Events
Total91/91 (100%)
Blood and lymphatic system disorders
ANAEMIA15/91 (16.5%)
LEUKOPENIA6/91 (6.6%)
NEUTROPENIA8/91 (8.8%)
Ear and labyrinth disorders
VERTIGO7/91 (7.7%)
Eye disorders
CONJUNCTIVAL HAEMORRHAGE6/91 (6.6%)
LACRIMATION INCREASED5/91 (5.5%)
PERIORBITAL OEDEMA31/91 (34.1%)
Gastrointestinal disorders
ABDOMINAL DISCOMFORT5/91 (5.5%)
ABDOMINAL DISTENSION5/91 (5.5%)
ABDOMINAL PAIN22/91 (24.2%)
ABDOMINAL PAIN UPPER6/91 (6.6%)
CONSTIPATION7/91 (7.7%)
DIARRHOEA57/91 (62.6%)
DYSPEPSIA14/91 (15.4%)
FLATULENCE12/91 (13.2%)
GASTROOESOPHAGEAL REFLUX DISEASE5/91 (5.5%)
NAUSEA65/91 (71.4%)
VOMITING34/91 (37.4%)
General disorders
CHILLS7/91 (7.7%)
FATIGUE45/91 (49.5%)
OEDEMA7/91 (7.7%)
OEDEMA PERIPHERAL18/91 (19.8%)
PAIN7/91 (7.7%)
PYREXIA9/91 (9.9%)
TEMPERATURE INTOLERANCE6/91 (6.6%)
Infections and infestations
SINUSITIS8/91 (8.8%)
UPPER RESPIRATORY TRACT INFECTION10/91 (11%)
URINARY TRACT INFECTION8/91 (8.8%)
Injury, poisoning and procedural complications
CONTUSION5/91 (5.5%)
Investigations
ALANINE AMINOTRANSFERASE INCREASED7/91 (7.7%)
ASPARTATE AMINOTRANSFERASE INCREASED10/91 (11%)
BLOOD BILIRUBIN INCREASED5/91 (5.5%)
BLOOD CREATININE INCREASED6/91 (6.6%)
NEUTROPHIL COUNT DECREASED6/91 (6.6%)
WEIGHT INCREASED9/91 (9.9%)
WHITE BLOOD CELL COUNT DECREASED5/91 (5.5%)
Metabolism and nutrition disorders
DECREASED APPETITE12/91 (13.2%)
HYPERGLYCAEMIA5/91 (5.5%)
HYPOKALAEMIA10/91 (11%)
HYPOMAGNESAEMIA6/91 (6.6%)
HYPOPHOSPHATAEMIA14/91 (15.4%)
Musculoskeletal and connective tissue disorders
ARTHRALGIA16/91 (17.6%)
BACK PAIN11/91 (12.1%)
JOINT SWELLING5/91 (5.5%)
MUSCLE SPASMS37/91 (40.7%)
MUSCULOSKELETAL CHEST PAIN5/91 (5.5%)
MUSCULOSKELETAL PAIN11/91 (12.1%)
MYALGIA8/91 (8.8%)
PAIN IN EXTREMITY13/91 (14.3%)
Nervous system disorders
DIZZINESS17/91 (18.7%)
DYSGEUSIA6/91 (6.6%)
HEADACHE20/91 (22%)
NEUROPATHY PERIPHERAL8/91 (8.8%)
PARAESTHESIA6/91 (6.6%)
SCIATICA5/91 (5.5%)
Psychiatric disorders
DEPRESSION8/91 (8.8%)
INSOMNIA8/91 (8.8%)
Respiratory, thoracic and mediastinal disorders
COUGH11/91 (12.1%)
DYSPNOEA11/91 (12.1%)
OROPHARYNGEAL PAIN6/91 (6.6%)
Skin and subcutaneous tissue disorders
ALOPECIA9/91 (9.9%)
DRY SKIN6/91 (6.6%)
NIGHT SWEATS7/91 (7.7%)
RASH24/91 (26.4%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

Other disclosure agreement that restricts the right of the PI to discuss or publish trial results after the trial is completed. The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (ie, data from all sites) in the clinical trial

Results Point of Contact

Name/TitleStudy Director
OrganizationNovartis Pharmaceuticals
Phone862-778-8300
EmailNovartis.email@novartis.com
Responsible Party:
Novartis Pharmaceuticals
ClinicalTrials.gov Identifier:
NCT00867113
Other Study ID Numbers:
  • CSTI571BUS282
First Posted:
Mar 23, 2009
Last Update Posted:
Mar 14, 2018
Last Verified:
Mar 1, 2018