Research

Memorial Sloan Kettering Cancer Center’s, Dr. Cristina Antonescu, Releases Presentation on GIST Cancer Research

Antonescu Research Lab Synopsis • A Proposal For 2018-2019 Funding

1. Investigate a novel method to screen whole genome copy number alterations through a multiplex sparse sequencing as a tool to identify genomic alterations in low to intermediate risk GIST patients. This method uses archival material and has the advantage of having a high turn-around time and being a rather unexpensive sequencing tool, which can replace the more laborious methods, such as conventional karyotyping or array CGH methods. Once identified, these additional genetic events will be used in conjunction to the routinely used mitotic count and KIT genotype to better select patients for adjuvant Gleevec, as well as more accurately inform regarding risk of malignancy. The proposed study includes a selected 35 low to intermediate risk GISTs with available DNA, genotype information and clinical data.

 
 
 
 
 
2. Our lab has been at the forefront of evaluating immune markers by immunohistochemistry as biomarkers for response to immune checkpoint inhibitors in various clinical trials. Pre and post-therapy biopsies are used as part of the immunotherapy correlative studies. We have available tissue biopsies from 2 on-going clinical trials where we are investigating the content and extent of immune infiltrates with various markers, such as PD-1 expression on CD4+ and CD8+ T cells, PDL1 and other additional markers. We are in the process of analyzing an algorithm based on the immune infiltrate in the pre-therapy tissue which can predict the response to these drugs. The method used is ‘multiplex immunohistochemistry with immunofluorescence analysis’.
 
 

Announcing the launch of our Web-Based Survey of Cognitive Dysfunction and Other Patient-Reported Outcomes in People with GIST.

This study is being conducted by Dr. Anette Duensing in collaboration with Drs. Dana Bovbjerg and Robert Ferguson (Biobehavioral Oncology Program, UPMC Hillman Cancer Center, University of Pittsburgh School of Medicine) and Dr. Beth Snitz (Department of Neurology, University of Pittsburgh School of Medicine).

Over the last months, this research initiative started after hearing patients with GIST complain about negative symptom experiences during long-term treatment, particularly with respect to cognitive function (similar to “Chemo brain”).

Cognitive symptoms and memory problems have been widely reported among survivors of certain cancers, particularly breast cancer. These memory problems may be mild or moderate but can nevertheless interfere with daily life. Memory difficulty has also been associated with mood disturbances that can affect quality of life.

Very little is known about cognitive dysfunction (difficulties with thinking and memory) for patients with GIST, particularly those who are taking tyrosine kinase inhibitors (TKIs), including Gleevec (Glivec). Most patients treated with TKIs have to maintain this therapy for an extended period of time and take it on a regular basis. This is different from patients with other cancers who are undergoing chemotherapy or radiation therapy. Their therapy is typically given in bouts over a few weeks or months.

We are asking GIST patients who are members of your online community and support groups to complete an online survey to help us to identify possible memory complaints in GIST patients on long-term TKI therapy.

 
 
 

Those who complete the survey must be 18 years of age or older. The survey is offered in English only at this time and includes questions about background (e.g., age, race, years of education, occupation), medical history and treatment regimens, perceived cognitive dysfunction and other symptoms as well as quality of life. The survey will take about 30 to 45 minutes to complete. No payment will be provided for completing the survey.

There are no foreseeable risks associated with this project, nor are there any direct benefits. This is an anonymous questionnaire, so responses will not identify anyone in any way. All responses will be kept confidential, and results will be kept in password-protected files. Participation is voluntary, and the survey may be stopped at any time.

Our goal is that results of this survey will lead to further research on the possible impact of TKI therapy on neurocognitive function. Most immediately, we hope that our study leads to tailoring of cognitive-behavioral therapy to counteract the cognitive effects of TKI treatment, using an approach that has been found to be effective in breast cancer survivors.

A pdf can be downloaded with more information on our survey. GIST Cognitive Dysfunction

Please note: The survey can only be taken once from any given IP address.

Anette Duensing, M.D.
Assistant Professor of Pathology
Cancer Therapeutics Program
UPMC Hillman Cancer Center

Clinical Trials

Clinical trials are important research studies that explore whether a particular medical strategy or treatment is safe and effective for GIST Cancer patients. These studies also may show which medical approaches work best for treating GIST cancer. The following trials are being held according to eligibility. Click the links for more information.

Oregon Health & Science University

Dr. Michael C. Heinrich

The following clinical trials are currently accepting new participants:

- A Phase 2, Open-Label Study to Assess the Safety and Efficacy of Oral MEK162 in Adults with Locally Advanced and Unresectable or Metastatic Malignant Cutaneous Melanoma, Harboring BRAF or NRAS Mutations

- A Phase 2 Study of CP-868,596 (crenolanib), a Selective and Potent Inhibitor of PDGFR, for the Treatment of Patients with Advanced Gastrointestinal Stromal Tumors with the D842V Mutation in the PDGFRA Gene

- An Open-Label, Randomised, Multi-Centre, Phase 2 Study to Investigate the Safety and Efficacy of AT13387, either as Monotherapy or in Combination with Imatinib, in Patients with Unresectable and/or Metastatic Malignant GIST whose Tumor has Progressed Following Treatment with a Maximum of Three Tyrosine Kinase Inhibitors

- An Open-Label Expanded Access Program of Regorafenib in Patients with Gastrointestinal Stromal Tumors (GIST) After Disease Progression On or Intolerance to Imatinib and Sunitinib
- A Phase 2 Study of OSI-906 in Pediatric and Adult Wild Type Gastrointestinal Stromal Tumors

Memorial Sloan Kettering Cancer Center

Dr. Ping Chi & Dr. William Tap

A Phase Ib/II Study of MEK162 in Combination with Imatinib Mesylate in Patients with Untreated Advanced Gastrointestinal Stromal Tumor (GIST)

Fox Chase Cancer Center

Dr. Margaret von Mehren

A Study of BLU-285 in Gastrointestinal Stromal Tumors (GIST) and other Solid Tumors.

This is a 2-part study. The first part is a dose-finding part to find the highest dose amount of the study drug with an acceptable level of safety and tolerability.

This part will also look at whether the study drug has any effect on tumors at the doses being used. The second part is an expansion part to check that the chosen dose of the study drug is safe and well tolerated. The part that you are being considered for will depend on which part of the study is open for enrollment.