Gastrointestinal Stromal TumorsPhase 2INV555NCT01172548
Safety and Efficacy Evaluation of Two Year Imatinib Treatment in Adjuvant Gastrointestinal Stromal Tumor (GIST)
A Phase 2 study testing imatinib mesylate in people with Gastrointestinal Stromal Tumors, run by Novartis Pharmaceuticals at 29 sites in 12 countries.
Trial summary
GISTs are the most common mesenchymal tumors of the gastrointestinal tract. Approximately 95% of GISTs are positive for KIT (CD117)-the receptor for stem cell factor (SCF). GISTs are not responsive to conventional cytotoxic chemotherapy and disease often recurs even after complete resection with wide margins. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Gastrointestinal Stromal Tumors
- What is being tested?
- imatinib mesylate
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 132 participants
- Where
- 29 sitesin 12 countries
- Study dates
- Aug 2008to Mar 2014
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Histologically proven diagnosis of primary GIST (without peritoneal or distant metastasis) with positive immunostaining for KIT (CD117);
- Undergone complete gross resection of a primary GIST within 70 days prior to enrollment (includes R0 [negative microscopic margins] and R1 [positive microscopic margins]);
- Intermediate or high risk of recurrence based on Corless criteria (Section 5.1):
Who cannot join
- Patient has received prior therapy with imatinib, or any other molecular targeted or biological therapy.
- Other protocol-defined inclusion/exclusion criteria may apply
Trial locations and contacts
29 sites in 12 countries.
29 sites in 12 countries
Russia6 sites
Novartis Investigative Site
Irkutsk, 664035
Novartis Investigative Site
Kazan', Tatarstan Republic, 420029
Novartis Investigative Site
Kursk, 305035
Novartis Investigative Site
Omsk, 644013
Novartis Investigative Site
Saint Petersburg, 198255
Novartis Investigative Site
Yekaterinburg, 620036
Taiwan6 sites
Novartis Investigative Site
Lin-Ko, 33305
Novartis Investigative Site
Niaosong Township, Taiwan, 83301
Novartis Investigative Site
Taichung, 40705
Novartis Investigative Site
Tainan, Taiwan ROC
Novartis Investigative Site
Taipei, Taiwan, ROC, 112
Novartis Investigative Site
Taipei, 10002
India4 sites
Novartis Investigative Site
Ahmedabad, Gujarat, 380009
Novartis Investigative Site
Mumbai, 400016
Novartis Investigative Site
New Delhi, 110044
Novartis Investigative Site
Pune, Maharashtra, 411 001
Thailand4 sites
Novartis Investigative Site
Bangkok, 10330
Novartis Investigative Site
Bangkok, 10400
Novartis Investigative Site
Bangkok, 10700
Novartis Investigative Site
Songkhla, 90110
Egypt2 sites
Novartis Investigative Site
Al Mansurah
Novartis Investigative Site
Cairo
About this study
Official title: A Multi-center, Single Arm, Phase II Study of Adjuvant Imatinib (Glivec®) in Patients Following the Resection of Primary Gastrointestinal Stromal Tumor ( GIST)
GISTs are the most common mesenchymal tumors of the gastrointestinal tract. Approximately 95% of GISTs are positive for KIT (CD117)-the receptor for stem cell factor (SCF). GISTs are not responsive to conventional cytotoxic chemotherapy and disease often recurs even after complete resection with wide margins.
Imatinib mesylate (trade names: Glivec® and Gleevec®, imatinib, formerly STI571) is a signal transduction inhibitor targeting several protein-tyrosine kinases that are believed to play a role in the proliferation of tumor cells. In the Phase II study of imatinib [CSTI571B 2222] in 147 patients with recurrent or metastatic GIST, the partial response rates were 67% and 66% in patients treated at 400 mg/d and 600 mg/d, respectively. Skin rash and elevated transaminases were the most common reason for drug discontinuation. The most frequently reported AEs were mild nausea, vomiting, diarrhea, superficial edema (primarily periorbital or lower limb), myalgia and muscle cramps. Grade 3/4 events included fluid retention (pleural or pericardial effusions, ascites, and pulmonary edema), skin rash, liver toxicity and gastrointestinal (GI) hemorrhage. Myelosuppression (neutropenia and thrombocytopenia) was a consistent finding. Also, a tumor lysis-like syndrome occurred in some patients leading to gastrointestinal (GI) and/or intratumoral hemorrhage.
Read more
In a Phase 3, American College of Surgeons Oncology Group trial (ACOSOG Z9001) of adjuvant imatinib, imatinib significantly improved 1-year recurrence-free survival (RFS) compared with placebo.
In summary, clinical trials have shown that imatinib produces clinical benefit in most patients with unresectable or metastatic GIST and extends median survival from 19 to 57 months. Imatinib is the standard of care for advanced GIST and has received regulatory approval for the treatment of unresectable or metastatic GIST. Studies suggest that adjuvant imatinib for 1 year prolongs RFS in patients at high risk of recurrent disease and metastases following complete surgical resection of the primary GIST.
Imatinib is an appealing adjuvant therapy for resected GIST because:
- Patients with primary GIST have a high chance of tumor recurrence
- Conventional adjuvant treatment modalities are ineffective
- Imatinib specifically inhibits the Kit receptor which is constitutively activated in most GISTs
- Imatinib inhibits the growth of Kit positive cells in vitro
- Imatinib is highly effective in many patients with advanced GIST in a Phase II trial
- Imatinib has been associated with minimal toxicity in patients with advanced GIST and in patients with chronic myelogenous leukemia (CML)
- Imatinib may have its greatest impact on survival when there is minimal disease.
Primary
- To assess Recurrence Free Survival Rate in patients with resected primary GIST who are treated with adjuvant imatinib for a duration of 2 years Secondary
- To compare Recurrence Free Survival, Overall Survival, and Time to Recurrence of patients with resected primary GIST who are treated with adjuvant imatinib for a duration of 2 years with historical data To assess the safety of imatinib given as adjuvant therapy for 2 years in patients with resected primary GIST
- Conditions
- Gastrointestinal Stromal Tumors
- Being tested
- imatinib mesylate
- Keywords
- Resected GIST, primary GIST, tumor recurrence, KIT receptor, KIT positive, advanced GIST, minimal toxicity, GIST
- Medical subject headings
- Gastrointestinal Stromal Tumors, Recurrence
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
imatinib mesylateDrug
Also called STI571, Gleevec/Glivec
| Study group | Role | What they receive |
|---|---|---|
| imatinib mesylate | Experimental | Not described Receives: Drug: imatinib mesylate |
What is being measured
The primary outcome is the main question the study is designed to answer.
Recurrence Free Survival Rate
Measured: 2 years
Secondary outcomes (5)
Compare Recurrence Free Survival Rate to historical controls
Measured: 2 years
Compare Overall Survival to historical controls
Measured: 2 years
Compare Time To Recurrence to historical controls
Measured: 2 years
Adverse Events
Measured: 2 years
Treatment Compliance - tracking if the patient is coming to visits as per visit schedule in protocol
Measured: 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Jul 2010 (estimated)
- Study startAug 2008
- Primary completionMar 2014
- Study completionMar 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Gastrointestinal Stromal TumorsStudies of the same condition, open and under way.
- More trials run by Novartis PharmaceuticalsThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Prevention
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 132 participants (actual)
Sponsor and investigators
- Lead sponsor
- Novartis Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Novartis Pharmaceuticals, Study director, Novartis Pharmaceuticals
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01172548
- Sponsor's protocol ID
- CSTI571BIC08
- Acronym
- INV555
- Status last verified
- May 2017
- First submitted
- 22 Jun 2010
- Last updated
- 31 May 2017
- Results posted
- No
Study at a glance
From the registry record, last updated by the sponsor on 31 May 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Multi-center, Single Arm, Phase II Study of Adjuvant Imatinib (Glivec®) in Patients Following the Resection of Primary Gastrointestinal Stromal Tumor ( GIST)
- ClinicalTrials.gov ID
- NCT01172548
- Acronym / sponsor ID
- INV555 / CSTI571BIC08
- Conditions
- Gastrointestinal Stromal Tumors
- Keywords
- Resected GIST, primary GIST, tumor recurrence, KIT receptor, KIT positive, advanced GIST, minimal toxicity, GIST
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 132 participants (actual)
- Lead sponsor
- Novartis PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- Aug 2008
- Primary completion
- Mar 2014 (actual)
- Study completion
- Mar 2014 (actual)
- First posted
- 29 Jul 2010 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
GISTs are the most common mesenchymal tumors of the gastrointestinal tract. Approximately 95% of GISTs are positive for KIT (CD117)-the receptor for stem cell factor (SCF). GISTs are not responsive to conventional cytotoxic chemotherapy and disease often recurs even after complete resection with wide margins.
Imatinib mesylate (trade names: Glivec® and Gleevec®, imatinib, formerly STI571) is a signal transduction inhibitor targeting several protein-tyrosine kinases that are believed to play a role in the proliferation of tumor cells. In the Phase II study of imatinib [CSTI571B 2222] in 147 patients with recurrent or metastatic GIST, the partial response rates were 67% and 66% in patients treated at 400 mg/d and 600 mg/d, respectively. Skin rash and elevated transaminases were the most common reason for drug discontinuation. The most frequently reported AEs were mild nausea, vomiting, diarrhea, superficial edema (primarily periorbital or lower limb), myalgia and muscle cramps. Grade 3/4 events included fluid retention (pleural or pericardial effusions, ascites, and pulmonary edema), skin rash, liver toxicity and gastrointestinal (GI) hemorrhage. Myelosuppression (neutropenia and thrombocytopenia) was a consistent finding. Also, a tumor lysis-like syndrome occurred in some patients leading to gastrointestinal (GI) and/or intratumoral hemorrhage.
In a Phase 3, American College of Surgeons Oncology Group trial (ACOSOG Z9001) of adjuvant imatinib, imatinib significantly improved 1-year recurrence-free survival (RFS) compared with placebo.
In summary, clinical trials have shown that imatinib produces clinical benefit in most patients with unresectable or metastatic GIST and extends median survival from 19 to 57 months. Imatinib is the standard of care for advanced GIST and has received regulatory approval for the treatment of unresectable or metastatic GIST. Studies suggest that adjuvant imatinib for 1 year prolongs RFS in patients at high risk of recurrent disease and metastases following complete surgical resection of the primary GIST.
Imatinib is an appealing adjuvant therapy for resected GIST because:
- Patients with primary GIST have a high chance of tumor recurrence
- Conventional adjuvant treatment modalities are ineffective
- Imatinib specifically inhibits the Kit receptor which is constitutively activated in most GISTs
- Imatinib inhibits the growth of Kit positive cells in vitro
- Imatinib is highly effective in many patients with advanced GIST in a Phase II trial
- Imatinib has been associated with minimal toxicity in patients with advanced GIST and in patients with chronic myelogenous leukemia (CML)
- Imatinib may have its greatest impact on survival when there is minimal disease.
Primary
- To assess Recurrence Free Survival Rate in patients with resected primary GIST who are treated with adjuvant imatinib for a duration of 2 years Secondary
- To compare Recurrence Free Survival, Overall Survival, and Time to Recurrence of patients with resected primary GIST who are treated with adjuvant imatinib for a duration of 2 years with historical data To assess the safety of imatinib given as adjuvant therapy for 2 years in patients with resected primary GIST
Study design
- Primary purpose
- Prevention
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| imatinib mesylate | Experimental | Drug: imatinib mesylate |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Histologically proven diagnosis of primary GIST (without peritoneal or distant metastasis) with positive immunostaining for KIT (CD117);
- Undergone complete gross resection of a primary GIST within 70 days prior to enrollment (includes R0 [negative microscopic margins] and R1 [positive microscopic margins]);
- Intermediate or high risk of recurrence based on Corless criteria (Section 5.1):
Key exclusion criteria (2 listed)
- Patient has received prior therapy with imatinib, or any other molecular targeted or biological therapy.
- Other protocol-defined inclusion/exclusion criteria may apply
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| imatinib mesylateAlso: STI571, Gleevec/Glivec | Drug | imatinib mesylate |
Primary outcome
Recurrence Free Survival Rate
Time frame: 2 years
5 secondary outcomes
Compare Recurrence Free Survival Rate to historical controls
Time frame: 2 years
Compare Overall Survival to historical controls
Time frame: 2 years
Compare Time To Recurrence to historical controls
Time frame: 2 years
Adverse Events
Time frame: 2 years
Treatment Compliance - tracking if the patient is coming to visits as per visit schedule in protocol
Time frame: 2 years
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 31 May 2017.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Novartis Pharmaceuticals study director
Novartis Pharmaceuticals
29 sites in 12 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing imatinib mesylate in people with Gastrointestinal Stromal Tumors, run by Novartis Pharmaceuticals at 29 sites in 12 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 2 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 31 May 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 29 sites in Russia, Taiwan, India, Thailand, Egypt and 7 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Recurrence Free Survival Rate (time frame: 2 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 31 May 2017.