Efficacy of Imatinib in Patients With Intermediate-risk Gastrointestinal Stromal Tumor With a High-risk Genomic Grade Index (GIGIST)
Primary Purpose
Gastrointestinal Stromal Tumor
Status
Unknown status
Phase
Phase 3
Locations
Study Type
Interventional
Intervention
Imatinib
Surveillance
Sponsored by
About this trial
This is an interventional diagnostic trial for Gastrointestinal Stromal Tumor
Eligibility Criteria
Inclusion Criteria:
- Man or woman 18 years old or over and PS:0-2
- No prior radiation therapy, no prior chemotherapy, no molecular targeted or biological therapy
- Subject with a gastrointestinal stromal tumor, intermediary risk from the Armed Forces Institute of Pathology classification [Miettenen 2006]
- Subject with Genomic Grade Index higher than 10 determined by CGH array;
- Subject with surgery for primary tumor performed from 2 weeks to 2 months before starting adjuvant Imatinib mesylate;
- Subject with no evidence of residual macroscopic disease after surgery (RO). Microscopically infiltrated margins, or supposed to be are allowed (R1)
- Subjects with absence of distant metastases
- Subject with a medical decision of treatment with its in accordance with imatinib marketed authorization.
Exclusion Criteria:
- Minors or pregnant or breast-feeding women.
- Subject with a contraindication to Imatinib, a known hypersensitivity to the active substance or to any of the excipients (ambivalence clause);
- Subject treated with medicinal products that induce CYP3A4;
- Subject who have experienced spontaneous tumor rupture before surgery (risk of spread);
- Subject whose tumor has a PDGFRA D842V mutation evidenced by sequencing from tumor block;
- Subject whose mutational status meets the wild phenotype definition as evidenced by sequencing from tumor block
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm Type
Active Comparator
Other
Arm Label
Standard Group
Experimental Group
Arm Description
The Standard Group will receive adjuvant imatinib at a dose of 400 mg per day for a period of 3 years. Patients will be assessed for metastases every three months for three years with thoraco-abdominal and pelvic CT scan.
The Experimental Group will receive the same thoraco-abdominal and pelvic CT scan. Surveillance
Outcomes
Primary Outcome Measures
Rate of metastatic relapse in GIST patient
The primary objective of this study is to assess the efficacy of adjuvant Imatinib on rate of metastatic relapse at 2 years in patients with intermediate-risk gastrointestinal stromal tumor presenting a high Genomic Grade Index.
Secondary Outcome Measures
Overall survival
Median in month(s)
Clinical and biological tolerance
Safety and tolerance will be assessed using the Common Terminology Criteria for Adverse Events (CTCAE) and Common Toxicity Criteria (CTC) at 15 days, 1 month and every three months. The investigator will grade all adverse events and severe adverse events (defined by the standard medical dictionary for regulatory activities, MedDRA) according to the NCI-CTCAE (version 4.0). Adverse events will be grouped by system organ classes.
Patients' quality of life
French version of the SF36. European Organization for Research and Treatment of Cancer QLQ-C30
Full Information
NCT ID
NCT02576080
First Posted
September 29, 2015
Last Updated
October 14, 2015
Sponsor
Assistance Publique Hopitaux De Marseille
1. Study Identification
Unique Protocol Identification Number
NCT02576080
Brief Title
Efficacy of Imatinib in Patients With Intermediate-risk Gastrointestinal Stromal Tumor With a High-risk Genomic Grade Index
Acronym
GIGIST
Official Title
Efficacy of Adjuvant Imatinib in Patients With Intermediate-risk Gastrointestinal Stromal Tumor With a High-risk Genomic Grade Index. Multicenter, Prospective, Randomized Study. Etude Multicentrique, Prospective, randomisée
Study Type
Interventional
2. Study Status
Record Verification Date
October 2015
Overall Recruitment Status
Unknown status
Study Start Date
October 2015 (undefined)
Primary Completion Date
October 2019 (Anticipated)
Study Completion Date
October 2020 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Assistance Publique Hopitaux De Marseille
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
Following the ACOSOG Z9001trial, imatinib received market authorization in Europe for patients with GIST at significant risk of relapse in the adjuvant setting, according to the classifications of Miettinen and Joensuu. Thereafter, the SSG XVIII / AI trial proved the need to revise the recommendations of the European Society for Medical Oncology regarding the optimal duration of treatment, which is currently three years. Patients at low risk of recurrence should not receive adjuvant treatment with imatinib and recommendations cannot be made from the literature data as to the indication of adjuvant treatment for patients with an intermediate risk of relapse. The provision of prognostic molecular markers in this group of so-called intermediate-risk subjects would facilitate the identification of responders to imatinib and avoid overtreating some patients and undertreating others who would benefit from Imatinib. Recently, Lagarde et al. have shown that the Genomic Index (GI = A ² / C, where A is the total number of alterations gains or losses and C is the number of chromosomes involved in these alterations in Comparative Genomic Hybridization array(CGH array)) could have prognostic value in GIST, particularly in intermediate risk GISTs. More recent work by the same author in 100 cases of GISTs with intermediate prognosis according to the classification of Miettinem identified two prognostic groups based on GI. The rate of metastatic relapse at 2 years was 30.6% in the group with GI greater than 10 versus 5.4% in the group with GI less than 10 (manuscript under preparation). Thus, it is legitimate to set up a randomized trial to study the effectiveness of adjuvant treatment with imatinib in the GIST population at intermediate risk of relapse and with a high GI. This study is a prospective randomized clinical trial: a phase III, open-label, 2 parallel groups, multicenter study. The primary objective of this study is to assess the efficacy of adjuvant Imatinib on rate of metastatic relapse at 2 years in patients with intermediate-risk gastrointestinal stromal tumor presenting a high Genomic Grade Index. The second objectives of this study are to compare the two therapeutic approaches in terms of metastasis-free survival at 1 year, 2 years and 3 years, overall survival, clinical and biological tolerance, safety and Quality of life of patients and caregivers. The eligible subjects must meet all of the following criteria : subject with a gastrointestinal stromal tumor, intermediary risk from the Armed Forces Institute of Pathology classification [Miettenen 2006], subject with Genomic Grade Index higher than 10 determined by CGH array, subject with surgery for primary tumor performed from 2 weeks to 2 months before starting adjuvant Imatinib mesylate, subject with no evidence of residual macroscopic disease after surgery and with a medical decision to prescribe imatinib. Subjects meeting any of the following criteria must not be enrolled : subject who have experienced spontaneous tumor rupture before surgery, subject whose tumor has a PDGFRA D842V mutation evidenced by sequencing from tumor Block and subject whose mutational status meets the wild phenotype definition as evidenced by sequencing from tumor Block.
The Standard Group will receive adjuvant imatinib at a dose of 400 mg per day for a period of 3 years. Patients will be assessed for metastases every three months for three years with thoraco-abdominal and pelvic CT scan. The Experimental Group will receive the same thoraco-abdominal and pelvic CT scan. The estimated proportion of subjects relapsing at 2 years will be 30% in the experimental group and 2.5% in the standard group: alpha risk, 5%, power 80%. A total of 80 subjects (40 in each arm) will be included. This is a trial combining two learned societies that already are taking part in many clinical trials in France (French Sarcoma Group and French Digestive Cancer Federation). The expected benefits for patients are : not treat subjects for whom this treatment would offer too little benefit weighed against the disadvantages and treat subjects in whom this treatment would provide a real benefit and reduce the cost of treatment in patients who would not benefit from being treated by imatinib. The originality of this study is that it will include molecular data in the therapeutic decision and demonstrate the concept of individualized treatment in this patient population. This could ultimately change the current recommendations.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Gastrointestinal Stromal Tumor
7. Study Design
Primary Purpose
Diagnostic
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
80 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Standard Group
Arm Type
Active Comparator
Arm Description
The Standard Group will receive adjuvant imatinib at a dose of 400 mg per day for a period of 3 years. Patients will be assessed for metastases every three months for three years with thoraco-abdominal and pelvic CT scan.
Arm Title
Experimental Group
Arm Type
Other
Arm Description
The Experimental Group will receive the same thoraco-abdominal and pelvic CT scan. Surveillance
Intervention Type
Drug
Intervention Name(s)
Imatinib
Intervention Type
Other
Intervention Name(s)
Surveillance
Intervention Description
The Experimental Group will receive the same thoraco-abdominal and pelvic CT scan.
Primary Outcome Measure Information:
Title
Rate of metastatic relapse in GIST patient
Description
The primary objective of this study is to assess the efficacy of adjuvant Imatinib on rate of metastatic relapse at 2 years in patients with intermediate-risk gastrointestinal stromal tumor presenting a high Genomic Grade Index.
Time Frame
5 years
Secondary Outcome Measure Information:
Title
Overall survival
Description
Median in month(s)
Time Frame
5 years
Title
Clinical and biological tolerance
Description
Safety and tolerance will be assessed using the Common Terminology Criteria for Adverse Events (CTCAE) and Common Toxicity Criteria (CTC) at 15 days, 1 month and every three months. The investigator will grade all adverse events and severe adverse events (defined by the standard medical dictionary for regulatory activities, MedDRA) according to the NCI-CTCAE (version 4.0). Adverse events will be grouped by system organ classes.
Time Frame
5 years
Title
Patients' quality of life
Description
French version of the SF36. European Organization for Research and Treatment of Cancer QLQ-C30
Time Frame
5 years
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Man or woman 18 years old or over and PS:0-2
No prior radiation therapy, no prior chemotherapy, no molecular targeted or biological therapy
Subject with a gastrointestinal stromal tumor, intermediary risk from the Armed Forces Institute of Pathology classification [Miettenen 2006]
Subject with Genomic Grade Index higher than 10 determined by CGH array;
Subject with surgery for primary tumor performed from 2 weeks to 2 months before starting adjuvant Imatinib mesylate;
Subject with no evidence of residual macroscopic disease after surgery (RO). Microscopically infiltrated margins, or supposed to be are allowed (R1)
Subjects with absence of distant metastases
Subject with a medical decision of treatment with its in accordance with imatinib marketed authorization.
Exclusion Criteria:
Minors or pregnant or breast-feeding women.
Subject with a contraindication to Imatinib, a known hypersensitivity to the active substance or to any of the excipients (ambivalence clause);
Subject treated with medicinal products that induce CYP3A4;
Subject who have experienced spontaneous tumor rupture before surgery (risk of spread);
Subject whose tumor has a PDGFRA D842V mutation evidenced by sequencing from tumor block;
Subject whose mutational status meets the wild phenotype definition as evidenced by sequencing from tumor block
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Sébastien SALAS, MD PhD
Phone
+33491384408
Email
sebastien.salas@ap-hm.fr
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Urielle DESALBRES
Organizational Affiliation
Assistance Publique Hopitaux De Marseille
Official's Role
Study Director
12. IPD Sharing Statement
Learn more about this trial
Efficacy of Imatinib in Patients With Intermediate-risk Gastrointestinal Stromal Tumor With a High-risk Genomic Grade Index
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