Clinical trial NCT01172548: Safety and Efficacy Evaluation of Two Year Imatinib Treatment in Adjuvant Gastrointestinal Stromal Tumor (GIST)
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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Gastrointestinal Stromal Tumors
Keywords: Resected GIST
primary GIST
tumor recurrence
KIT receptor
KIT positive
advanced GIST
minimal toxicity
GIST
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2010-07-29
Enrollment: 132
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: PREVENTION

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


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.

Other protocol-defined inclusion/exclusion criteria may apply

Primary outcomes:
measure: Recurrence Free Survival Rate
timeFrame: 2 years
Secondary outcomes:
measure: Compare Recurrence Free Survival Rate to historical controls
timeFrame: 2 years
measure: Compare Overall Survival to historical controls
timeFrame: 2 years
measure: Compare Time To Recurrence to historical controls
timeFrame: 2 years
measure: Adverse Events
timeFrame: 2 years
measure: Treatment Compliance - tracking if the patient is coming to visits as per visit schedule in protocol
timeFrame: 2 years
Other outcomes:
Locations:
city: Alger
country: Algeria
facility: Novartis Investigative Site
city: Cairo
country: Egypt
facility: Novartis Investigative Site
city: Mansoura
country: Egypt
facility: Novartis Investigative Site
city: Ahmedabad
country: India
facility: Novartis Investigative Site
state: Gujrat
city: Pune
country: India
facility: Novartis Investigative Site
state: Maharashtra
city: Mumbai
country: India
facility: Novartis Investigative Site
city: New Delhi
country: India
facility: Novartis Investigative Site
city: Amman
country: Jordan
facility: Novartis Investigative Site
city: Beirut
country: Lebanon
facility: Novartis Investigative Site
city: Kazan
country: Russian Federation
facility: Novartis Investigative Site
state: Tatarstan Republic
city: Ekaterinburg
country: Russian Federation
facility: Novartis Investigative Site
city: Irkutsk
country: Russian Federation
facility: Novartis Investigative Site
city: Kursk
country: Russian Federation
facility: Novartis Investigative Site
city: Omsk
country: Russian Federation
facility: Novartis Investigative Site
city: St. Petersburg
country: Russian Federation
facility: Novartis Investigative Site
city: Riyadh
country: Saudi Arabia
facility: Novartis Investigative Site
city: Parktown
country: South Africa
facility: Novartis Investigative Site
city: Tainan 704
country: Taiwan
facility: Novartis Investigative Site
state: Taiwan ROC
city: Taipei
country: Taiwan
facility: Novartis Investigative Site
state: Taiwan, ROC
city: Lin-Ko
country: Taiwan
facility: Novartis Investigative Site
city: Niaosong Township
country: Taiwan
facility: Novartis Investigative Site
city: Taichung
country: Taiwan
facility: Novartis Investigative Site
city: Taipei
country: Taiwan
facility: Novartis Investigative Site
city: Bangkok
country: Thailand
facility: Novartis Investigative Site
city: Bangkok
country: Thailand
facility: Novartis Investigative Site
city: Bangkok
country: Thailand
facility: Novartis Investigative Site
city: Songkla
country: Thailand
facility: Novartis Investigative Site
city: Tunis
country: Tunisia
facility: Novartis Investigative Site
city: Ankara
country: Turkey
facility: Novartis Investigative Site
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References: