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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:
NCT01172548
First received: June 22, 2010
Last updated: October 19, 2014
Last verified: October 2014
  Purpose

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 Intervention Phase
Gastrointestinal Stromal Tumors
Drug: imatinib mesylate
Phase 4

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: 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)

Resource links provided by NLM:


Further study details as provided by Novartis:

Primary Outcome Measures:
  • Recurrence Free Survival Rate [ Time Frame: 2 years ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Compare Recurrence Free Survival Rate to historical controls [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  • Compare Overall Survival to historical controls [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  • Compare Time To Recurrence to historical controls [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  • Adverse Events [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
  • Treatment Compliance - tracking if the patient is coming to visits as per visit schedule in protocol [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]

Enrollment: 132
Study Start Date: August 2008
Study Completion Date: March 2014
Primary Completion Date: March 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: imatinib mesylate Drug: imatinib mesylate
Other Names:
  • STI571
  • Gleevec/Glivec

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01172548

  Hide Study Locations
Locations
Algeria
Novartis Investigative Site
Alger, Algeria, 016000
Egypt
Novartis Investigative Site
Cairo, Egypt
Novartis Investigative Site
Mansoura, Egypt
India
Novartis Investigative Site
Ahmedabad, Gujrat, India, 380009
Novartis Investigative Site
Pune, Maharashtra, India, 411 001
Novartis Investigative Site
Mumbai, India, 400016
Novartis Investigative Site
New Delhi, India, 110044
Jordan
Novartis Investigative Site
Amman, Jordan
Lebanon
Novartis Investigative Site
Beirut, Lebanon, 1107 2020
Russian Federation
Novartis Investigative Site
Kazan, Tatarstan Republic, Russian Federation, 420029
Novartis Investigative Site
Ekaterinburg, Russian Federation, 620036
Novartis Investigative Site
Irkutsk, Russian Federation, 664035
Novartis Investigative Site
Kursk, Russian Federation, 305035
Novartis Investigative Site
Omsk, Russian Federation, 644013
Novartis Investigative Site
St. Petersburg, Russian Federation, 198255
Saudi Arabia
Novartis Investigative Site
Riyadh, Saudi Arabia, 11211
South Africa
Novartis Investigative Site
Parktown, South Africa, 2193
Taiwan
Novartis Investigative Site
Tainan 704, Taiwan ROC, Taiwan
Novartis Investigative Site
Taipei, Taiwan, ROC, Taiwan, 112
Novartis Investigative Site
Lin-Ko, Taiwan, 33305
Novartis Investigative Site
Niaosong Township, Taiwan, 83301
Novartis Investigative Site
Taichung, Taiwan, 40705
Novartis Investigative Site
Taipei, Taiwan, 10002
Thailand
Novartis Investigative Site
Bangkok, Thailand, 10330
Novartis Investigative Site
Bangkok, Thailand, 10400
Novartis Investigative Site
Bangkok, Thailand, 10700
Novartis Investigative Site
Songkla, Thailand, 90110
Tunisia
Novartis Investigative Site
Tunis, Tunisia, 1006
Turkey
Novartis Investigative Site
Ankara, Turkey, 06100
Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
  More Information

No publications provided

Responsible Party: Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier: NCT01172548     History of Changes
Other Study ID Numbers: CSTI571BIC08
Study First Received: June 22, 2010
Last Updated: October 19, 2014
Health Authority: United States: Food and Drug Administration
Egypt: Ministry of Health and Population
Algeria: Ministry of Health
Morocco: Ministry of Public Health
Tunisia: Ministry of Public Health
India: Ministry of Health
Jordan: JFDA (Jordan Food and Drug Administration)
Lebanon: Ministry of Public Health
Russia: Ministry of Health of the Russian Federation
Saudi Arabia: Ministry of Health
South Africa: Medicines Control Council
Taiwan: Department of Health
Thailand: Food and Drug Administration
Turkey: Ministry of Health

Keywords provided by Novartis:
Resected GIST
primary GIST
tumor recurrence
KIT receptor
KIT positive
advanced GIST
minimal toxicity
GIST

Additional relevant MeSH terms:
Gastrointestinal Stromal Tumors
Neoplasms
Digestive System Diseases
Digestive System Neoplasms
Gastrointestinal Diseases
Gastrointestinal Neoplasms
Neoplasms by Histologic Type
Neoplasms, Connective Tissue
Neoplasms, Connective and Soft Tissue
Imatinib
Antineoplastic Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Protein Kinase Inhibitors
Therapeutic Uses

ClinicalTrials.gov processed this record on November 24, 2014