Safety and Efficacy Evaluation of Two Year Imatinib Treatment in Adjuvant Gastrointestinal Stromal Tumor (GIST) (INV555)

Study Description

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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

Condition or disease	Intervention/treatment	Phase
Gastrointestinal Stromal Tumors	Drug: imatinib mesylate	Phase 2

Study Design

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Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	132 participants
Intervention Model:	Single Group Assignment
Masking:	None (Open Label)
Primary Purpose:	Prevention
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)
Study Start Date :	August 2008
Actual Primary Completion Date :	March 2014
Actual Study Completion Date :	March 2014

Arms and Interventions

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Arm	Intervention/treatment
Experimental: imatinib mesylate	Drug: imatinib mesylate; Other Names: STI571; Gleevec/Glivec

Outcome Measures

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Primary Outcome Measures :

1. Recurrence Free Survival Rate [ Time Frame: 2 years ]

Secondary Outcome Measures :

1. Compare Recurrence Free Survival Rate to historical controls [ Time Frame: 2 years ]
2. Compare Overall Survival to historical controls [ Time Frame: 2 years ]
3. Compare Time To Recurrence to historical controls [ Time Frame: 2 years ]
4. Adverse Events [ Time Frame: 2 years ]
5. Treatment Compliance - tracking if the patient is coming to visits as per visit schedule in protocol [ Time Frame: 2 years ]

Eligibility Criteria

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Ages Eligible for Study:	18 Years and older (Adult, Senior)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

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.

Other protocol-defined inclusion/exclusion criteria may apply

Contacts and Locations

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  Show 29 Study Locations

Sponsors and Collaborators

Novartis Pharmaceuticals

Investigators

Study Director:	Novartis Pharmaceuticals	Novartis Pharmaceuticals

More Information

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Additional Information:

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

See results for CSTI571BIC08 at Novartis Clinical Trials Database 

Responsible Party:	Novartis Pharmaceuticals
ClinicalTrials.gov Identifier:	NCT01172548 History of Changes
Other Study ID Numbers:	CSTI571BIC08
First Posted:	July 29, 2010
Last Update Posted:	May 31, 2017
Last Verified:	May 2017

Keywords provided by Novartis ( Novartis Pharmaceuticals ):

Resected GIST; primary GIST; tumor recurrence; KIT receptor	KIT positive; advanced GIST; minimal toxicity; GIST

Additional relevant MeSH terms:

Gastrointestinal Stromal Tumors; Neoplasms, Connective Tissue; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms	Digestive System Diseases; Gastrointestinal Diseases; Imatinib Mesylate; Antineoplastic Agents; Protein Kinase Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action