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

NCT ID: NCT01172548

Last Updated: 2017-05-31

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 132 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2008-08-31
• Study Completion Date: 2014-03-31

Brief 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

Conditions

Gastrointestinal Stromal Tumors

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: PREVENTION
• Blinding Strategy: NONE

Study Groups

imatinib mesylate

Group Type: EXPERIMENTAL

imatinib mesylate

Intervention Type: DRUG

Interventions

imatinib mesylate

Intervention Type: DRUG

Other Intervention Names

STI571; Gleevec/Glivec

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Novartis Pharmaceuticals

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Novartis Pharmaceuticals

Role: STUDY_DIRECTOR

Novartis Pharmaceuticals

Locations

Novartis Investigative Site

Algiers, , Algeria

Novartis Investigative Site

Al Mansurah, , Egypt

Novartis Investigative Site

Cairo, , Egypt

Novartis Investigative Site

Ahmedabad, Gujarat, India

Novartis Investigative Site

Pune, Maharashtra, India

Novartis Investigative Site

Mumbai, , India

Novartis Investigative Site

New Delhi, , India

Novartis Investigative Site

Amman, , Jordan

Novartis Investigative Site

Beirut, , Lebanon

Novartis Investigative Site

Kazan', Tatarstan Republic, Russia

Novartis Investigative Site

Irkutsk, , Russia

Novartis Investigative Site

Kursk, , Russia

Novartis Investigative Site

Omsk, , Russia

Novartis Investigative Site

Saint Petersburg, , Russia

Novartis Investigative Site

Yekaterinburg, , Russia

Novartis Investigative Site

Riyadh, , Saudi Arabia

Novartis Investigative Site

Parktown, , South Africa

Novartis Investigative Site

Niaosong Township, Taiwan, Taiwan

Novartis Investigative Site

Tainan City, Taiwan ROC, Taiwan

Novartis Investigative Site

Taipei, Taiwan, ROC, Taiwan

Novartis Investigative Site

Lin-Ko, , Taiwan

Novartis Investigative Site

Taichung, , Taiwan

Novartis Investigative Site

Taipei, , Taiwan

Novartis Investigative Site

Bangkok, , Thailand

Novartis Investigative Site

Bangkok, , Thailand

Novartis Investigative Site

Bangkok, , Thailand

Novartis Investigative Site

Songkhla, , Thailand

Novartis Investigative Site

Tunis, , Tunisia

Novartis Investigative Site

Ankara, , Turkey (Türkiye)

Countries

Algeria; Egypt; India; Jordan; Lebanon; Russia; Saudi Arabia; South Africa; Taiwan; Thailand; Tunisia; Turkey (Türkiye)

Related Links

http://meetinglibrary.asco.org/content/92196-114

J Clin Oncol 30, 2012 (suppl; abstr e20514) (From 2012 ASCO Annual Meeting )

Other Identifiers

CSTI571BIC08

Identifier Type: -

Identifier Source: org_study_id