Role of Surgery in Patients With Focally Progressive Gastrointestinal Stromal Tumors (GISTs) After Imatinib Treatment

Role of Surgery in Patients With Focally Progressive Gastrointestinal Stromal Tumors (GISTs) After Imatinib Treatment: A Prospective, Multicenter, Randomized Trial

This study evaluates the efficacy and safety of surgical intervention in patients with focally progressive GISTs after imatinib treatment. The enrolled patients will be randomized to receive surgery following imatinib 400 milligram per day (MG/d) or only tyrosine kinase inhibitor (Imatinib 600 MG/d or Sunitinib 37.5 MG/d).

Study Overview

• Status: Unknown
• Conditions: Surgery; Gastrointestinal Stromal Tumors
• Intervention / Treatment: Procedure: surgery; Drug: Imatinib 400 MG; Drug: Imatinib escalation; Drug: Sunitinib

Detailed Description

Imatinib is the first-line treatment for advanced GIST with a satisfactory response rate, but complete remission rarely happens. Besides, drug resistance can occur during the treatment and the median time of drug resistance is about 20-24 months. Once drug resistance occurs, the patient's condition will progress rapidly. As a salvage treatment, the effect of increasing the dose of imatinib or switching to sunitinib is very limited. Progress after imatinib treatment usually involves two conditions, focal progression and extensive progression. For local progression, all resistant lesions can be completely resected; extensive progression refers to resistance progression in multiple sites, and progressive lesions cannot be completely removed. The present study is aimed to assess the benefits of surgical resection of imatinib-resistant lesions in patients with localized disease.

• Study Type: Interventional
• Enrollment (Anticipated): 92
• Phase: Not Applicable

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Patients whose pathology is clearly diagnosed as recurrent/metastatic GIST, have undergone standardized imatinib treatment, and the disease progresses during the treatment;
2. The lesions with progress are confined to one organ, and the number is ≤3; after evaluation by relevant professional surgeons or multidisciplinary team discussion, it is considered that the progressive lesions can be completely and safely removed without affecting the organ function;
3. Age: 18 years old ≤ age ≤ 75 years old;
4. No other malignant tumors occurred within five years;
5. Eastern Cooperative Oncology Group (ECOG) physical status score <2 points;
6. American Society of Anesthesiologists (ASA) score <3 points;
7. There are no restrictions on gender and race;
8. Patients with informed consent.

Exclusion Criteria:

1. The patient has other serious comorbidities and cannot tolerate surgery: such as severe cardiopulmonary disease, cardiac function in grade 2 or lower, pulmonary infection, moderate to severe chronic obstructive pulmonary disease (COPD), etc., combined with severe diabetes and/or kidney Insufficient function, combined with severe hepatitis and/or functional Child-pugh grade C or a grade B that is clearly difficult to correct, combined with severe malnutrition;
2. Patients with extensive disease progress;
3. Imatinib primary resistant patients;
4. Patients with other diseases requiring simultaneous surgical intervention, such as gallstones; inguinal hernia;
5. Disease-related complications such as bleeding, perforation, and obstruction;
6. Pregnant or lactating women;
7. The patient has a serious mental illness;
8. Patients with other malignant tumors within five years;
9. The patient has participated in or is participating in other clinical studies or is using other tyrosinekinase inhibitors.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Surgery following imatinib; Surgery requires at least removal of all drug-resistant lesions. Imatinib 400 MG/d should be taken once the patients resume oral diet.	Procedure: surgery; Surgery requires at least removal of all drug-resistant lesions.; Drug: Imatinib 400 MG; Imatinib 400 MG/d should be taken once the patients resume oral diet
Active Comparator: Imatinib escalation or sunitinib; Escalation of imatinib or replacement of sunitinib are both conventional salvage treatments for imatinib-resistant GISTs. There is no high-level evidence to suggest which method is better. So patients are free to choose imatinib 600 MG/d or sunitinib 37.5 MG/d	Drug: Imatinib escalation; Imatinib 600 MG/d; Drug: Sunitinib; Sunitinib 37.5 MG/d

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-free Survival	Progression-free survival will be defined as time from the start of treatment until progression (documented according to Response Evaluation Criteria in Solid Tumors (RECIST) criteria and defined as at least a 20% increase in the sum of the longest diameter of target lesions) or death, whichever comes first.	one year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival	Overall survival will be defined as time from the start of treatment until death from any cause	one year

Collaborators and Investigators

• Sponsor: Shanghai Zhongshan Hospital

Study record dates

Study Major Dates

• Study Start (Anticipated): July 1, 2019
• Primary Completion (Anticipated): June 1, 2021
• Study Completion (Anticipated): December 1, 2021

Study Registration Dates

• First Submitted: February 27, 2019
• First Submitted That Met QC Criteria: March 1, 2019
• First Posted (Actual): March 5, 2019

Study Record Updates

• Last Update Posted (Actual): March 5, 2019
• Last Update Submitted That Met QC Criteria: March 1, 2019
• Last Verified: February 1, 2019

More Information

Terms related to this study

• Keywords: Gastrointestinal Stromal Tumors; imatinib-resistant; focal progression
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Neoplasms, Connective Tissue; Gastrointestinal Stromal Tumors; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Protein Kinase Inhibitors; Sunitinib; Imatinib Mesylate
• Other Study ID Numbers: B2018-297

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No