Safety and Efficacy Evaluation of Two Year Imatinib Treatment in Adjuvant Gastrointestinal Stromal Tumor (GIST)

Gastrointestinal Stromal Tumors Clinical Trial

— INV555  

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01172548
• Other study ID #: CSTI571BIC08
• Status: Completed
• Phase: Phase 2
• First received: June 22, 2010
• Last updated: May 28, 2017
• Start date: August 2008
• Est. completion date: March 2014

Study information

• Verified date: May 2017
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical 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.

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:

1. Patients with primary GIST have a high chance of tumor recurrence

2. Conventional adjuvant treatment modalities are ineffective

3. Imatinib specifically inhibits the Kit receptor which is constitutively activated in most GISTs

4. Imatinib inhibits the growth of Kit positive cells in vitro

5. Imatinib is highly effective in many patients with advanced GIST in a Phase II trial

6. Imatinib has been associated with minimal toxicity in patients with advanced GIST and in patients with chronic myelogenous leukemia (CML)

7. 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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 132
• Est. completion date: March 2014
• Est. primary completion date: March 2014
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• 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):

Exclusion Criteria:

• Patient has received prior therapy with imatinib, or any other molecular targeted or biological therapy.

Other protocol-defined inclusion/exclusion criteria may apply

Related Conditions & MeSH terms

• Gastrointestinal Stromal Tumors

Intervention

Drug:
• imatinib mesylate

Locations

Country	Name	City	State
Algeria	Novartis Investigative Site	Alger
Egypt	Novartis Investigative Site	Cairo
Egypt	Novartis Investigative Site	Mansoura
India	Novartis Investigative Site	Ahmedabad	Gujrat
India	Novartis Investigative Site	Mumbai
India	Novartis Investigative Site	New Delhi
India	Novartis Investigative Site	Pune	Maharashtra
Jordan	Novartis Investigative Site	Amman
Lebanon	Novartis Investigative Site	Beirut
Russian Federation	Novartis Investigative Site	Ekaterinburg
Russian Federation	Novartis Investigative Site	Irkutsk
Russian Federation	Novartis Investigative Site	Kazan	Tatarstan Republic
Russian Federation	Novartis Investigative Site	Kursk
Russian Federation	Novartis Investigative Site	Omsk
Russian Federation	Novartis Investigative Site	St. Petersburg
Saudi Arabia	Novartis Investigative Site	Riyadh
South Africa	Novartis Investigative Site	Parktown
Taiwan	Novartis Investigative Site	Lin-Ko
Taiwan	Novartis Investigative Site	Niaosong Township
Taiwan	Novartis Investigative Site	Taichung
Taiwan	Novartis Investigative Site	Tainan 704	Taiwan ROC
Taiwan	Novartis Investigative Site	Taipei	Taiwan, ROC
Taiwan	Novartis Investigative Site	Taipei
Thailand	Novartis Investigative Site	Bangkok
Thailand	Novartis Investigative Site	Bangkok
Thailand	Novartis Investigative Site	Bangkok
Thailand	Novartis Investigative Site	Songkla
Tunisia	Novartis Investigative Site	Tunis
Turkey	Novartis Investigative Site	Ankara

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Countries where clinical trial is conducted

Algeria,  Egypt,  India,  Jordan,  Lebanon,  Russian Federation,  Saudi Arabia,  South Africa,  Taiwan,  Thailand,  Tunisia,  Turkey, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Recurrence Free Survival Rate		2 years
Secondary	Compare Recurrence Free Survival Rate to historical controls		2 years
Secondary	Compare Overall Survival to historical controls		2 years
Secondary	Compare Time To Recurrence to historical controls		2 years
Secondary	Adverse Events		2 years
Secondary	Treatment Compliance - tracking if the patient is coming to visits as per visit schedule in protocol		2 years

External Links

•   See results for CSTI571BIC08 at Novartis Clinical Trials Database