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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT00237185




Registration number
NCT00237185
Ethics application status
Date submitted
9/10/2005
Date registered
12/10/2005
Date last updated
19/08/2014

Titles & IDs
Public title
A Study of the Efficacy and Safety of Imatinib Mesylate in Patients With Unresectable or Metastatic Gastrointestinal Stromal Tumors Expressing C-kit Gene
Scientific title
Open, Randomized, Phase II Study of Glivec in Patients With Unresectable or Metastatic Gastrointestinal Stromal Tumors Expressing C-kit Plus 10 Year Extension Study
Secondary ID [1] 0 0
CSTI571B2222/E1
Secondary ID [2] 0 0
CSTI571B2222
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Unresectable or Metastatic Malignant Gastrointestinal Stromal Tumor (GIST) 0 0
Condition category
Condition code
Cancer 0 0 0 0
Stomach
Cancer 0 0 0 0
Bowel - Small bowel (duodenum and ileum)
Cancer 0 0 0 0
Bowel - Back passage (rectum) or large bowel (colon)

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Imatinib mesylate

Experimental: imatinib mesylate 400 mg - 400 mg once daily

Experimental: imatinib mesylate 600 mg - 600 mg once daily


Treatment: Drugs: Imatinib mesylate
Participants were randomized 1:1 to receive imatinib mesylate 400 mg/day or 600 mg/day. Upon unsatisfactory treatment effect on the starting dose of 400 mg/day or 600 mg/day imatinib mesylate, in the opinion of the treating physician, a dose increase up to 600 mg/day or 800 mg/day, was allowed provided that the participant continued to benefit from the treatment and in the absence of safety concerns.

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Best Tumor Response (Core) - Best tumor response was based on the Southwestern Oncology Group (SWOG) criteria. Objective tumor response assessments were categorized according to the following criteria: complete response (CR), partial response (PR), no change or stable disease (SD), progression of disease (PD), unknown where the progression has not been documented and one or more measurable or evaluable sites have not been assessed (UNK), status after resection for progression (RP), status after resection for safety (RS), status after preventive resection (RPR), progressive after first resection (PDR) and not evaluable. Any tumor assessment after surgical resection for preventative reasons was treated like tumor assessments of UNK for calculation of best response. Tumor assessments with current objective status = RP, RS or PDR were treated like assessments with objective tumor status = PD n the calculation of best response.
Timepoint [1] 0 0
Month 36
Primary outcome [2] 0 0
Best Tumor Response (Core + Extension) - Best tumor response was based on the Southwestern Oncology Group (SWOG) criteria. Objective tumor response assessments were categorized according to the following criteria: complete response (CR), partial response (PR), no change or stable disease (SD), progression of disease (PD), unknown where the progression has not been documented and one or more measurable or evaluable sites have not been assessed (UNK), status after resection for progression (RP), status after resection for safety (RS), status after preventive resection (RPR), progressive after first resection (PDR) and not evaluable. Any tumor assessment after surgical resection for preventative reasons was treated like tumor assessments of UNK for calculation of best response. Tumor assessments with current objective status = RP, RS or PDR were treated like assessments with objective tumor status = PD n the calculation of best response.
Timepoint [2] 0 0
Month 156
Secondary outcome [1] 0 0
Overall Survival (Core) - Overall survival was analyzed as time to event for all participants. Participants who did not die were censored at the last date known alive, which is the last date of any study medication, laboratory sample, tumor assessment, adverse event end date or date of last contact.
Timepoint [1] 0 0
Date of first imatinib dose to the date of death during the core period, up to 36 months.
Secondary outcome [2] 0 0
Overall Survival (Core + Extension) - Overall survival was analyzed as time to event for all participants. Participants who did not die were censored at the last date known alive, which is the last date of any study medication, laboratory sample, tumor assessment, adverse event end date or date of last contact.
Timepoint [2] 0 0
Date of first imatinib dose to the date of death during the core and extension periods, up to 156 months.
Secondary outcome [3] 0 0
Duration of Response (Core) - Duration of response was analyzed as time to event for all participants whose best response was at least a PR. The onset of response was the first tumor assessment that was subsequently confirmed to constitute at least a partial best response. The end of response was the first tumor assessment noting PD.
Timepoint [3] 0 0
Date of confirmed best PR or CR to date of confirmed disease progression during the core period, up to 36 months.
Secondary outcome [4] 0 0
Duration of Response (Core + Extension) - Duration of response was analyzed as time to event for all participants whose best response was at least a PR. The onset of response was the first tumor assessment that was subsequently confirmed to constitute at least a partial best response. The end of response was the first tumor assessment noting PD.
Timepoint [4] 0 0
Date of confirmed best PR or CR to date of confirmed disease progression during the core and extension periods, up to 156 months
Secondary outcome [5] 0 0
Progression Free Survival (PFS) (Core + Extension) - Progression free survival was analyzed as a time to event for each participant. If a participant had no event, then the PFS was censored at the last tumor assessment.
Timepoint [5] 0 0
Date of first imatinib dose to earliest date of progression, resection due to safety/progression, death due to any cause or discontinuation due to unsatisfactory therapeutic effect during the core and extension periods, up to 156 months.
Secondary outcome [6] 0 0
Time to Treatment Failure (Core) - Time to treatment failure was analyzed as time to event for all participants. Participants who had neither progressed, died nor discontinued from the trial for any reason other than the condition no longer required therapy were censored for analysis ate the time of their last tumor assessment.
Timepoint [6] 0 0
Date of first imatinib dose to date of earliest occurrence of progression, death due to any cause, or discontinuation from the trial for any reason other than the condition no longer required therapy during the core period, up to 36 months.
Secondary outcome [7] 0 0
Time to Treatment Failure (Core + Extension) - Time to treatment failure was analyzed as time to event for all participants. Participants who had neither progressed, died nor discontinued from the trial for any reason other than the condition no longer required therapy were censored for analysis at the time of their last tumor assessment.
Timepoint [7] 0 0
Date of first imatinib dose to date of earliest occurrence of progression, death due to any cause, or discontinuation from the trial for any reason other than the condition no longer required therapy during the core and extension periods, up to 156 month.
Secondary outcome [8] 0 0
Time to Onset of Response (Core) - Time to response was analyzed as time to event for all participants. Participants who did not meet the definition of confirmed PR/CR were censored at the time of their last progression-free tumor assessment.
Timepoint [8] 0 0
Date of first imatinib dose to the date of the first tumor assessment that was later confirmed to be at least a partial response during the core period, up to 36 months.
Secondary outcome [9] 0 0
Time to Onset of Response (Core + Extension) - Time to response was analyzed as time to event for all participants. Participants who did not meet the definition of confirmed PR/CR were censored at the time of their last progression-free tumor assessment.
Timepoint [9] 0 0
Date of first imatinib dose to the date of the first tumor assessment that was later confirmed to be at least a partial response during the core and extension periods, up to 156 months.
Secondary outcome [10] 0 0
Time to Progression (Core + Extension) - Time to progression was analyzed as time to event for all participants. Participants who had neither progressed, died nor discontinued from the trial for any reason other than the condition no longer required therapy were censored for analysis at the time of their last tumor assessment.
Timepoint [10] 0 0
Date of first imatinib dose to date of progression or death due to disease indication or discontinuation due to unsatisfactory therapeutic effect during the core and extension periods, up to 156 months.

Eligibility
Key inclusion criteria
- Men and non-pregnant women =18 years of age with the histopathologically documented
diagnosis of malignant GIST that was unresectable and/or metastatic. Confirmation of
KIT (CD117) expression via immunohistochemical analysis of tumor sample was also
required

- At least one measurable lesion, as defined by Southwestern Oncology Group (SWOG) Solid
Tumor Response Criteria, which had not been previously embolized or irradiated

- Performance status =3 as defined by the Eastern Cooperative Oncology Group (ECOG)
criteria, as well as a life expectancy =6 months and adequate end organ function
defined as follows: Total bilirubin <1.5 times upper limit of normal (ULN), aspartate
aminotransferase (SGOT) and alanine aminotransferase (SGPT) <2.5 x ULN (or <5 x ULN if
hepatic metastases were present), creatinine <1.5 x ULN, absolute neutrophil count
(ANC) >1.5 x 10^9/L, platelet count >100 x 10^9/L
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- Patients with fewer than five years of disease-free survival from any other (non-GIST)
malignancy except if the other malignancy was not currently clinically significant and
did not require active intervention or if the other malignancy was a basal cell skin
cancer or a cervical carcinoma in situ

- Patients with known brain metastases

- Evidence of any of the following disorders: Grade III/IV cardiac failure as defined by
the New York Heart Association Criteria, severe concomitant disease, acute or known
chronic liver disease (i.e. chronic active hepatitis, cirrhosis) or HIV infection

- Chemotherapy or other investigational therapy within four weeks prior to study entry
(six weeks for nitrosourea or mitomycin-C) and/or radiotherapy to =25% of the bone
marrow

- Inability to cooperate

- Major surgery within two weeks or exposure to other investigational agents within 28
days of entry into the study

Other protocol-defined inclusion / exclusion criteria may have applied.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 0 0
Novartis Investigative Site - Geelong
Recruitment postcode(s) [1] 0 0
3220 - Geelong
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Massachusetts
Country [2] 0 0
United States of America
State/province [2] 0 0
Oregon
Country [3] 0 0
United States of America
State/province [3] 0 0
Pennsylvania
Country [4] 0 0
Finland
State/province [4] 0 0
Helsinki

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Novartis Pharmaceuticals
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
In the core study, participants with unresectable or metastatic gastrointestinal stromal
tumors expressing c-kit were treated with either 400 mg or 600 mg imatinib mesylate for 3
years. The 10 year extension study allowed participants, who successfully completed the core
study, to continue study treatment with imatinib mesylate provided they still benefited from
treatment and did not demonstrate safety concerns as per the investigator's opinion.
Trial website
https://clinicaltrials.gov/show/NCT00237185
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Novartis Pharmaceuticals
Address 0 0
Novartis Pharmaceuticals
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Summary results
Other publications