Inclusion Criteria

DISEASE CHARACTERISTICS:

- 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

- Patients will be stratified into Pediatric and Adult cohorts (age at diagnosis)

- Pediatric cohort: age at diagnosis ≤ 18 years OR diagnosis of Carney Triad or
Carney-Stratakis Diad (paraganglioma, pulmonary chondroma)

- Must have received at least sunitinib malate (sunitinib) and have had
progression on or intolerance to therapy

- 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

- Patients must have measurable disease defined as lesions that can be measured in 2
dimensions by medical-imaging techniques such as computed tomography (CT) or magnetic
resonance imaging (MRI); ascites, pleural fluid, and lesions seen on positron
emission tomography (PET) scan only are not considered measurable

- Patients with known brain metastases should be excluded from this clinical trial

PATIENT CHARACTERISTICS:

- Eastern Cooperative Oncology Group (ECOG) performance status 0-2

- White blood cell count ≥ 2.0 x 10^9/L

- Absolute neutrophil count (ANC) ≥ 1.5 x 10^9/L (≥ 14 days off growth factors)

- Platelet count ≥ 75 x 10^9/L

- Total bilirubin ≤ 1.5 times the upper limit of normal (ULN) for age

- Alanine aminotransferase (ALT)/aspartate aminotransferase (AST) (serum glutamic
pyruvate transaminase [SGPT]/serum glutamic oxaloacetic transaminase [SGOT]) ≤ 3
times the ULN for the reference lab (≤ 5 times the ULN for the reference lab in the
presence of known hepatic metastasis, adjusted for age)

- Creatinine clearance > 70 mL/min OR serum creatinine < 1.5 times ULN per age and
gender

- QTc interval < 450 msec at baseline

- No significant cardiac disease

- Fasting blood glucose < 150 mg/dL at baseline

- Glycosylated hemoglobin (HbA1c) < 7% at screening

- Patients with diabetes mellitus should have controlled disease on oral medications,
defined as no diabetic ketoacidosis (hyperglycemia, ketonuria, pH < 7.3, and
bicarbonate < 15 mEq/L) at the time of enrollment or within 30 days prior to
enrollment

- No change in oral medications greater than 10% within 30 days prior to
enrollment

- No patients with diabetes mellitus requiring insulin for control of their
diabetes

- Patient must be able to swallow to participate in the study

- No history of allergic reactions attributed to compounds of similar chemical or
biologic composition to OSI-906

- No uncontrolled intercurrent illness including, but not limited to, ongoing or active
infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac
arrhythmia, or psychiatric illness/social situations that would limit compliance with
study requirements

- Pregnant women are excluded from this study and breastfeeding should be discontinued

- No fertile men and women of childbearing potential not employing an effective method
of birth control throughout the trial and for 3 months after last study drug
administration in both sexes; women of childbearing potential must have a negative
pregnancy test (serum β-HCG) within the 7 days prior to study drug administration

- Women of childbearing potential includes both pre-menopausal women and women
within the first 2 years of the onset of menopause

- Effective methods of birth control include: surgically sterile, barrier device
(condom, diaphragm), contraceptive coil, abstinence; oral contraceptives (OCPs)
alone are not considered an effective method

- Known human immunodeficiency virus (HIV)-positive patients on combination
antiretroviral therapy are ineligible

- No patients with a history of liver cirrhosis

PRIOR CONCURRENT THERAPY:

- See Disease Characteristics

- No concomitant drugs that prolong the QTc interval

- Time elapsed from previous therapy must be ≥ 3 weeks except for prior tyrosine kinase
inhibitor therapy, which can be ≥ 7 days; patients must be recovered from the effects
of any prior surgery, radiotherapy, or systemic therapy

- No patients who are receiving any other investigational agents or other anti-cancer
therapies other than those administered in this study during protocol treatment

- Use of the potent CYP1A2 inhibitors ciprofloxacin and fluvoxamine are prohibited;
other less potent CYP1A2 inhibitors/inducers are not excluded

- No prior treatment with another kinase inhibitor targeting IGF-1R pathway

- Use of drugs that have a known risk of causing Torsades de Pointes (TdP) are
prohibited within 14 days prior to initiation of linsitinib

- Patients with a history of solid organ transplant are ineligible

- Patients requiring palliative radiotherapy will be discontinued from study drug

- Surgery done for progressive symptom management will be considered evidence of
progressive disease and patients will be removed from study

- Patients that are deemed appropriate for surgical debulking because of response
or prolonged stable disease will be allowed to undergo resection without being
removed from study as long as:

- They do not undergo complete resection

- They have had stable or responding disease for > 9 months

- Patients who undergo surgical resection prior to 9 months who do not
have evidence of progressive disease will be removed from study