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SSG XXV: The Stop-GIST Trial; Discontinuation of Imatinib in Patients With Oligo-metastatic GIST

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ClinicalTrials.gov Identifier: NCT02924714
Recruitment Status : Recruiting
First Posted : October 5, 2016
Last Update Posted : April 10, 2018
Sponsor:
Information provided by (Responsible Party):
Øyvind Sverre Bruland, Oslo University Hospital

Tracking Information
First Submitted Date  ICMJE October 4, 2016
First Posted Date  ICMJE October 5, 2016
Last Update Posted Date April 10, 2018
Study Start Date  ICMJE January 2017
Estimated Primary Completion Date November 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: October 4, 2016)
Progression free survival (PFS) [ Time Frame: 3 years ]
Three-year progression-free survival (PFS) after discontinuation of imatinib.
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT02924714 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: October 6, 2016)
  • Overall survival (OS) [ Time Frame: 3 years ]
    Overall survival will be measured from the date of discontinuation of imatinib to the date of death resulting from any cause.
  • Quality of Life (QoL) [ Time Frame: 3 years ]
    EQ-5D
Original Secondary Outcome Measures  ICMJE
 (submitted: October 4, 2016)
  • Overall survival (OS) [ Time Frame: 3 years ]
    Overall survival will be measured from the date of discontinuation of imatinib to the date of death resulting from any cause.
  • Quality of Life (QoL) [ Time Frame: 3 years ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE SSG XXV: The Stop-GIST Trial; Discontinuation of Imatinib in Patients With Oligo-metastatic GIST
Official Title  ICMJE Discontinuation of Imatinib in Patients With Oligo-metastatic Gastrointestinal Stromal Tumor That Has Become Radiologically Undetectable With Treatment
Brief Summary The trial "The stop-GIST trial" is an Oslo University Hospital sponsored, prospective, open-label, 1-group, multicenter phase II trial evaluating discontinuation of imatinib in highly selected patients treated with imatinib longer than 5 years for oligo-metastatic GIST (≤ 3 metastases) and who have no detectable overt GIST lesions on CT/MRI imaging following complete surgical resection (R0/R1-resection) or radiofrequency ablation (RFA) of the metastases.
Detailed Description Patients with metastatic GIST are currently recommended to have life-long treatment with tyrosine kinase inhibitors (TKI). The standard first-line treatment is imatinib, which is switched to other drugs at progression or if the patient does not tolerate imatinib. The prevailing hypothesis is that imatinib and other TKIs fail to completely eradicate metastatic GIST and that progression is inevitable if imatinib treatment is discontinued. However, the SSGXVIII/AIO trial found that 3 years of adjuvant imatinib yielded both superior RFS and OS rates compared to 1 year of adjuvant imatinib, which finding does not exclude the hypothesis that sufficiently long administration of imatinib might sometimes eradicate subclinical GIST. Furthermore, a few retrospective studies have reported favorable survival outcomes with surgery of residual disease in metastatic GIST in patients responding to imatinib, and a subset (approximately 20%) of patients with advanced GIST do not progress within the first 10 years on imatinib. Imatinib treatment comes with potential side-effects and, as of now, considerable costs to the society. Therefore, discontinuation of imatinib in highly selected patients, i.e. those who have received imatinib for longer than 5 years and who have undergone metastasectomy of all macroscopic oligometastatic disease, needs to be explored as a novel treatment strategy. Discontinuation might lead to detection of durable complete remissions without imatinib or even cure.
Study Type  ICMJE Interventional
Study Phase  ICMJE Not Applicable
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Other
Condition  ICMJE Gastrointestinal Stromal Tumor
Intervention  ICMJE Other: Discontinuation of imatinib
Study Arms  ICMJE Discontinuation of imatinib
Patients treated with imatinib longer than 5 years for oligo-metastatic GIST (≤ 3 metastases) and who have no longer detectable GIST lesions on CT/MRI imaging following complete surgical resection (R0/R1-resection) or RFA of the metastases are assigned to discontinue imatinib.
Intervention: Other: Discontinuation of imatinib
Publications * Hompland I, Bruland ØS. Can Imatinib Be Safely Withdrawn in Patients with Surgically Resected Metastatic GIST? Anticancer Res. 2015 Nov;35(11):5759-65. Review.

*   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 Recruiting
Estimated Enrollment  ICMJE
 (submitted: October 4, 2016)
31
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE November 2022
Estimated Primary Completion Date November 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. Age ≥ 18.
  2. Morphological and immunohistochemical documentation of GIST (immunostaining for KIT/ (CD117) and/or DOG-1 (anoctamin-1)) must be positive on a tumour sample. Patients with demonstrated mutation in KIT or PDGFRA may be entered to the study despite negative immunostaining for KIT and DOG-1 provided that tumour histology is compatible with GIST.
  3. Confirmed metastatic disease by radiology, histology, or both in history.
  4. >5.0 years of treatment with imatinib for metastatic disease when the breaks in imatinib administration are taken into account.
  5. No more than 3 detectable metastases in the liver and/or in the abdomen on imaging of the abdomen and the pelvis or at surgery during the course of the disease.
  6. Macroscopically complete resection of all metastases (either R0 or R1 surgery). Patients who have microscopically infiltrated margins (or suspected microscopical infiltration, R1) are eligible to enter the study. Radiofrequency ablation (RFA) of liver metastases in place of surgery is also allowed. Patients whose oligometastatic disease had disappeared completely so that no remaining target lesion for surgery or RFA can be identified (including absence of residual cyst-like lesions) are allowed to enter the study.
  7. Eastern Co-operative Oncology Group (ECOG) performance status ≤ 2.
  8. Patient has provided a written, voluntary informed consent prior to study entry and any study-specific procedures.

Exclusion Criteria:

  1. Patients with metastases outside of the abdomen (e.g. in the bones or lungs).
  2. Not willing to donate tumor tissue and/or blood samples for the molecular studies that aim at predicting of GIST recurrence.
  3. Presence of a mutation in SDH, or other evidence for SDH deficiency.
  4. Presence of neurofibromatosis-1.
  5. R2 resection of the primary tumour or metastasis.
  6. Patient with inability to grant reliable informed consent.
  7. Inability to comply with the scheduled follow-up.
  8. Progressive disease during imatinib or other systemic treatments for GIST, before or after surgery/RFA of the metastases.

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Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Øyvind S Bruland, MD PhD 22934767 ext 47 osb@ous-hf.no
Contact: Ivar Hompland, MD 22931236 ext 47 ivahom@ous-hf.no
Listed Location Countries  ICMJE Norway
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02924714
Other Study ID Numbers  ICMJE SSG XXV: Stop-GIST
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Øyvind Sverre Bruland, Oslo University Hospital
Study Sponsor  ICMJE Oslo University Hospital
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Heikki Joensuu, MD PhD Comprehensive Cancer Center Helsinki
Principal Investigator: Øyvind S Bruland, MD PhD Oslo University Hospital
PRS Account Oslo University Hospital
Verification Date April 2018

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