Surgery in Gastrointestinal Stromal Tumors (GISTs) for Treatment, Tumor Modeling, and Genomic Analysis

Background:

Gastrointestinal stromal tumors (GISTs) are the most common gastrointestinal soft tissue

sarcoma, but remain a rare disease entity.

Most GISTs are characterized by KIT or PDGFRA mutations, making them susceptible to

tyrosine kinase inhibitor (TKI) therapy.

Wild-type (WT) GISTs are rarer tumors, usually characterized by SDH mutations and/or lack

of KIT or PDGFRA mutations; paragangliomas are frequently associated with WT GISTs.

Non-WT GISTs may become refractory to TKI therapy, whereas WT GISTs are generally

resistant to TKI therapy.

The primary treatment modality for GISTs is surgical resection, which may involve the

stomach, liver, and/or peritoneal surfaces; most patients will require multiple

operations to remove disease not responsive to systemic agents.

Investigational systemic therapies are limited by toxicity and/or lack of efficacy,

resulting in an unmet need for novel treatment options.

Obtaining fresh tumor tissue is critical to the successful development of GIST models for

drug research, as well as for next generation tumor genomic sequencing, and to help

identify novel targets and/or agents for the treatment of WT and TKI-resistant non-WT

GISTs.

Objective:

Evaluate and follow participants with GISTs, particularly WT and treatment-refractory

non-WT, to support translational research for this rare disease

Assess disease-free intervals (DFIs) between surgical resection of disease for at least 5

years

Eligibility:

Participants with histologically confirmed or clinical presentation suspicious of GIST.

Design:

Prospective cohort study

Participants with histologically confirmed or clinical presentation suspicious of GIST

will enroll on study and will have active surveillance every 9-15 months for up to 10

years prior to and up to 5 years after surgical resection and/or cytoreduction. As

participants may have multiple resections during the course of the study, 5-year

surveillance post-surgery may be initiated multiple times, relative to the last resection

performed.

All participants enrolled will be evaluated for tumor resection or cytoreduction at the

start of study and if appropriate, will be offered surgery, otherwise they will be on

active surveillance until surgical resection or cytoreduction is clinically indicated.

It is expected that approximately 30-40 participants per year may enroll on this trial;

the accrual ceiling will be set at 400 to permit accrual over a 10-year period.