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

NCT01172548 | Completed Phase 2

• 1 other identifier: CSTI571BIC08
• Study Type: interventional
• Target: 132
• Locations: 11 countries
• Sites: 28

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:

• 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

Keywords

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

Outcome Measures

Primary Outcomes (1)

• Recurrence Free Survival Rate

  2 years

Secondary Outcomes (5)

• Compare Recurrence Free Survival Rate to historical controls

  2 years

• Compare Overall Survival to historical controls

  2 years

• Compare Time To Recurrence to historical controls

  2 years

• Adverse Events

  2 years

• Treatment Compliance - tracking if the patient is coming to visits as per visit schedule in protocol

  2 years

Study Arms (1)

imatinib mesylate

EXPERIMENTAL

Drug: imatinib mesylate

Interventions

imatinib mesylate DRUG

Also known as: STI571, Gleevec/Glivec

imatinib mesylate

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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):

You may not qualify if:

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

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (29)

Novartis Investigative Site

Algiers, 016000, Algeria

Location

Novartis Investigative Site

Al Mansurah, Egypt

Location

Novartis Investigative Site

Cairo, Egypt

Location

Novartis Investigative Site

Ahmedabad, Gujarat, 380009, India

Location

Novartis Investigative Site

Pune, Maharashtra, 411 001, India

Location

Novartis Investigative Site

Mumbai, 400016, India

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Novartis Investigative Site

New Delhi, 110044, India

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Novartis Investigative Site

Amman, Jordan

Location

Novartis Investigative Site

Beirut, 1107 2020, Lebanon

Location

Novartis Investigative Site

Kazan', Tatarstan Republic, 420029, Russia

Location

Novartis Investigative Site

Irkutsk, 664035, Russia

Location

Novartis Investigative Site

Kursk, 305035, Russia

Location

Novartis Investigative Site

Omsk, 644013, Russia

Location

Novartis Investigative Site

Saint Petersburg, 198255, Russia

Location

Novartis Investigative Site

Yekaterinburg, 620036, Russia

Location

Novartis Investigative Site

Riyadh, 11211, Saudi Arabia

Location

Novartis Investigative Site

Parktown, 2193, South Africa

Location

Novartis Investigative Site

Niaosong Township, Taiwan, 83301, Taiwan

Location

Novartis Investigative Site

Tainan, Taiwan ROC, Taiwan

Location

Novartis Investigative Site

Taipei, Taiwan, ROC, 112, Taiwan

Location

Novartis Investigative Site

Lin-Ko, 33305, Taiwan

Location

Novartis Investigative Site

Taichung, 40705, Taiwan

Location

Novartis Investigative Site

Taipei, 10002, Taiwan

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Novartis Investigative Site

Bangkok, 10330, Thailand

Location

Novartis Investigative Site

Bangkok, 10400, Thailand

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Novartis Investigative Site

Bangkok, 10700, Thailand

Location

Novartis Investigative Site

Songkhla, 90110, Thailand

Location

Novartis Investigative Site

Tunis, 1006, Tunisia

Location

Novartis Investigative Site

Ankara, 06100, Turkey (Türkiye)

Location

MeSH Terms

Conditions

Gastrointestinal Stromal Tumors; Recurrence

Interventions

Imatinib Mesylate

Condition Hierarchy (Ancestors)

Neoplasms, Connective Tissue; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Benzamides; Amides; Organic Chemicals; Benzoates; Acids, Carbocyclic; Carboxylic Acids; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Piperazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pyrimidines

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 22, 2010
• First Posted: July 29, 2010
• Study Start: August 1, 2008
• Primary Completion: March 1, 2014
• Study Completion: March 1, 2014
• Last Updated: May 31, 2017

Record last verified: 2017-05

Locations

TW (6); TU (1); TH (4); LE (1); AL (1); SA (1); IN (4); EG (2); RU (6); ZA (1); JO (1)