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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
Assistance Publique Hopitaux De Marseille
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional diagnostic trial for Gastrointestinal Stromal Tumor

Eligibility Criteria

18 Years - 80 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

    First Posted
    September 29, 2015
    Last Updated
    October 14, 2015
    Sponsor
    Assistance Publique Hopitaux De Marseille
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    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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