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

Primary Purpose

Gastrointestinal Stromal Tumor

Status

Suspended

Phase

Not Applicable

Locations

Norway

Study Type

Interventional

Intervention

Discontinuation of imatinib

About this trial

This is an interventional other trial for Gastrointestinal Stromal Tumor focused on measuring GIST

Eligibility Criteria

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

Inclusion Criteria:

Age ≥ 18.
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.
Confirmed metastatic disease by radiology, histology, or both in history.
>5.0 years of treatment with imatinib for metastatic disease when the breaks in imatinib administration are taken into account.
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.
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.
Eastern Co-operative Oncology Group (ECOG) performance status ≤ 2.
Patient has provided a written, voluntary informed consent prior to study entry and any study-specific procedures.

Exclusion Criteria:

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

Sites / Locations

Oslo University Hospital

Arms of the Study

Arm 1

Arm Type

Other

Arm Label

Discontinuation of imatinib

Arm Description

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.

Outcomes

Primary Outcome Measures

Progression free survival (PFS)

Three-year progression-free survival (PFS) after discontinuation of imatinib.

Secondary Outcome Measures

Overall survival (OS)

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)

EQ-5D

Full Information

NCT ID

NCT02924714

First Posted

October 4, 2016

Last Updated

February 7, 2022

Sponsor

Oslo University Hospital

1. Study Identification

Unique Protocol Identification Number

NCT02924714

Brief Title

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

Official Title

Discontinuation of Imatinib in Patients With Oligo-metastatic Gastrointestinal Stromal Tumor That Has Become Radiologically Undetectable With Treatment

Study Type

Interventional

2. Study Status

Record Verification Date

February 2022

Overall Recruitment Status

Suspended

Why Stopped

Slow accrual

Study Start Date

January 2017 (undefined)

Primary Completion Date

November 2022 (Anticipated)

Study Completion Date

November 2022 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Oslo University Hospital

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Gastrointestinal Stromal Tumor

Keywords

GIST

7. Study Design

Primary Purpose

Other

Study Phase

Not Applicable

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

31 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Discontinuation of imatinib

Arm Type

Other

Arm Description

Intervention Type

Other

Intervention Name(s)

Discontinuation of imatinib

Primary Outcome Measure Information:

Title

Progression free survival (PFS)

Description

Three-year progression-free survival (PFS) after discontinuation of imatinib.

Time Frame

3 years

Secondary Outcome Measure Information:

Title

Overall survival (OS)

Description

Overall survival will be measured from the date of discontinuation of imatinib to the date of death resulting from any cause.

Time Frame

3 years

Title

Quality of Life (QoL)

Description

EQ-5D

Time Frame

3 years

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Age ≥ 18. 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. Confirmed metastatic disease by radiology, histology, or both in history. >5.0 years of treatment with imatinib for metastatic disease when the breaks in imatinib administration are taken into account. 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. 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. Eastern Co-operative Oncology Group (ECOG) performance status ≤ 2. Patient has provided a written, voluntary informed consent prior to study entry and any study-specific procedures. Exclusion Criteria: Patients with metastases outside of the abdomen (e.g. in the bones or lungs). Not willing to donate tumor tissue and/or blood samples for the molecular studies that aim at predicting of GIST recurrence. Presence of a mutation in SDH, or other evidence for SDH deficiency. Presence of neurofibromatosis-1. R2 resection of the primary tumour or metastasis. Patient with inability to grant reliable informed consent. Inability to comply with the scheduled follow-up. Progressive disease during imatinib or other systemic treatments for GIST, before or after surgery/RFA of the metastases. -

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Heikki Joensuu, MD PhD

Organizational Affiliation

Comprehensive Cancer Center Helsinki

Official's Role

Study Director

First Name & Middle Initial & Last Name & Degree

Øyvind S Bruland, MD PhD

Organizational Affiliation

Oslo University Hospital

Official's Role

Principal Investigator

Facility Information:

Facility Name

Oslo University Hospital

City

Oslo

Country

Norway

12. IPD Sharing Statement

Citations:

PubMed Identifier

26503996

Citation

Hompland I, Bruland OS. Can Imatinib Be Safely Withdrawn in Patients with Surgically Resected Metastatic GIST? Anticancer Res. 2015 Nov;35(11):5759-65.

Results Reference

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

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