GIST Support Wiki

New Trial: Linsitinib in Treating Younger and Adult Patients With Gastrointestinal Stromal Tumors

3/26/2012 I contacted Dr George at DFCi about this trial. She anticipates the Fox Chase site opening first. It is still not listed on the DFCI website although they plan to have it eventually.

From Marina: > A few years ago Dr. Corless gave a presentation at ASCO that indicated that "wild type" GISTs in older adults are quite variable in their expression levels of IGF1R.

Only some cases of adult "wild type" GIST have high levels of IGF1R expression, while other cases if not most case do not.

Meanwhile, "wild type" GISTs in young patients most always have elevated levels of IGFIR. It was also stated that IGF1R is not mutated in wild type GIST.

IGF1 is an important regulator of childhood growth of bone and skeletal muscle, and in this context, it's not surprising that pediatric GIST and other pediatric tumors may have a tendency for higher level of IGF1/IGF1R expression than adult tumors in general.

A Phase 2 Study of OSI-906 (lasitinib) in Pediatric and Adult Patients With Wild Type Gastrointestinal Stromal Tumors

OUTLINE: This is a multicenter study. Patients are stratified according to age (≤ 18 years vs > 18 years) and diagnosis of Carney Triad or Carney-Stratakis Diad (paraganglioma, pulmonary chondroma) (yes vs no).

Patients receive linsitinib orally (PO) twice daily (BID) on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Estimated Enrollment: 40 Study Start Date: March 2012 Estimated Primary Completion Date: March 2013 (Final data collection date for primary outcome measure)

Ages Eligible for Study: 15 Years and older

•Patients must have histologically confirmed gastrointestinal stromal tumor (GIST) with confirmed genotype of wild-type in a Clinical Laboratory Improvement Amendments (CLIA)-certified laboratory

◦At a minimum, mutation analysis should include exons 9, 11, 13, and 17 of KIT and exons 12 and 18 of PDGFRA


United States, California Stanford Comprehensive Cancer Center - Palo Alto Recruiting Palo Alto, California, United States, 94304-1812 Contact: Neyssa M. Marina, MD 650-723-5535

United States, Maryland NCI - Pediatric Oncology Branch Recruiting Bethesda, Maryland, United States, 20892-1106 Contact: Lee J. Helman, MD 301-496-4257

United States, Massachusetts Dana-Farber/Harvard Cancer Center at Dana-Farber Cancer Institute Recruiting Boston, Massachusetts, United States, 02115 Contact: Annick D. Van den Abbeele, MD 617-632-2595

United States, Michigan University of Michigan Comprehensive Cancer Center Recruiting Ann Arbor, Michigan, United States, 48109-0942 Contact: Clinical Trials Office - University of Michigan Comprehensive 800-865-1125

United States, Oregon Knight Cancer Institute at Oregon Health and Science University Recruiting Portland, Oregon, United States, 97239-3098 Contact: Clinical Trials Office - Knight Cancer Institute at Oregon Hea 503-494-1080

United States, Pennsylvania Fox Chase Cancer Center - Philadelphia Recruiting Philadelphia, Pennsylvania, United States, 19111-2497 Contact: Clinical Trials Office - Fox Chase Cancer Center - Philadelphi 215-728-4790 United States, Texas

M. D. Anderson Cancer Center at University of Texas Recruiting Houston, Texas, United States, 77030-4009 Contact: Clinical Trials Office - M. D. Anderson Cancer Center at the U 713-792-3245

MARINA: The key question is whether high expression of IGFIR in a GIST tumor is a requisite to expect a benefit from blocking IGF1R receptor with linistinib?? This would be something to ask Dr. Heinrich. I have my own opinion that it would seem relevant, but I'd be only guessing. Alternatively, we could hypothesize an autocrine or paracrine stimulation of normal levels of IGF1R receptor. .....But, who knows.....

The protocol does not require documentation of high IGF1R expression for patients who wish to enroll. The protocol also does not explicitly require mutational testing of B-Raf, although we know a small percentage of "wild type" GISTs are actually B-Raf mutant GIST. I would not expect IGF1R inhibition to be effective against B-Raf mutant GIST based on observing R K 'S situation.

I would imagine that you could arrange for tumors to be tested for IGF1R expression, and B-Raf mutational status.

Below are comments in the trial protocol. Someone over 18 yrs would need to have had progression on Gleevec, and confirmation that key exons in KIT and PDGFRA are not mutated.

""◦At a minimum, mutation analysis should include exons 9, 11, 13, and 17 of KIT and exons 12 and 18 of PDGFRA""

""Adult cohort: age at diagnosis > 18 years AND no diagnosis of Carney Triad or Carney-Stratakis Diad

■Must have had progression on or intolerance to imatinib mesylate (imatinib) therapy as documented by treating physician""