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Efficacy of Imatinib in Patients With Intermediate-risk Gastrointestinal Stromal Tumor With a High-risk Genomic Grade Index (GIGIST)

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ClinicalTrials.gov Identifier: NCT02576080
Recruitment Status : Not yet recruiting
First Posted : October 15, 2015
Last Update Posted : October 15, 2015
Sponsor:
Information provided by (Responsible Party):
Assistance Publique Hopitaux De Marseille

Tracking Information
First Submitted Date  ICMJE September 29, 2015
First Posted Date  ICMJE October 15, 2015
Last Update Posted Date October 15, 2015
Study Start Date  ICMJE October 2015
Estimated Primary Completion Date October 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: October 14, 2015)
Rate of metastatic relapse in GIST patient [ Time Frame: 5 years ]
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.
Original Primary Outcome Measures  ICMJE Same as current
Change History No Changes Posted
Current Secondary Outcome Measures  ICMJE
 (submitted: October 14, 2015)
  • Overall survival [ Time Frame: 5 years ]
    Median in month(s)
  • Clinical and biological tolerance [ Time Frame: 5 years ]
    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 [ Time Frame: 5 years ]
    French version of the SF36. European Organization for Research and Treatment of Cancer QLQ-C30
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Efficacy of Imatinib in Patients With Intermediate-risk Gastrointestinal Stromal Tumor With a High-risk Genomic Grade Index
Official Title  ICMJE 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
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.

Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Diagnostic
Condition  ICMJE Gastrointestinal Stromal Tumor
Intervention  ICMJE
  • Drug: Imatinib
  • Other: Surveillance
    The Experimental Group will receive the same thoraco-abdominal and pelvic CT scan.
Study Arms  ICMJE
  • Active Comparator: Standard Group
    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.
    Intervention: Drug: Imatinib
  • Experimental Group
    The Experimental Group will receive the same thoraco-abdominal and pelvic CT scan. Surveillance
    Intervention: Other: Surveillance
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Not yet recruiting
Estimated Enrollment  ICMJE
 (submitted: October 14, 2015)
80
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE October 2020
Estimated Primary Completion Date October 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 80 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Sébastien SALAS, MD PhD +33491384408 sebastien.salas@ap-hm.fr
Listed Location Countries  ICMJE Not Provided
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02576080
Other Study ID Numbers  ICMJE 2014-31
2014-005255-87 ( EudraCT Number )
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Assistance Publique Hopitaux De Marseille
Study Sponsor  ICMJE Assistance Publique Hopitaux De Marseille
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Urielle DESALBRES Assistance Publique Hopitaux De Marseille
PRS Account Assistance Publique Hopitaux De Marseille
Verification Date October 2015

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP