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

Phase 2
18 Years
Not Enrolling
Carney Complex, Gastrointestinal Stromal Tumor, Paraganglioma, Sarcoma

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Trial Information

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



- To determine the response rate (complete response [CR] and partial response [PR]) to
treatment with linsitinib (OSI-906) in patients with advanced wild-type (WT)
gastrointestinal stromal tumor (GIST) as determined by Response Evaluation Criteria in
Solid Tumors (RECIST) 1.1.


- To determine the clinical benefit rate (stable disease [SD] ≥ 9 months, PR, or CR) in
patients with advanced WT GIST treated with linsitinib.

- To determine the response duration, progression-free survival (PFS), and overall
survival in patients with advanced WT GIST treated with linsitinib.

- To determine the tolerability and adverse event profile of linsitinib in patients with
advanced GIST.

- To explore patterns of protein expression in serum and tumor tissues as predictors of
response and PFS in advanced WT GIST treated with linsitinib.

- To evaluate the metabolic response to linsitinib using fludeoxyglucose F 18
(FDG)-positron emission tomography (PET).

- To determine if tumor metabolic response correlates with anatomic response and clinical

- To measure changes in tumor metabolism by FDG-PET qualitatively and semi-quantitatively
with standard uptake value (SUV) and tumor body ratio (TBR) from baseline to first
computed tomography (CT)-response evaluation and correlate the findings with size
changes as defined by conventional cross-sectional imaging scans. (exploratory)

- To investigate correlations between glucose, insulin, and candidate tumor tissue and
blood biomarkers with FDG-PET metabolic response. (exploratory)

OUTLINE: This is a multicenter study. Patients are stratified according to type of
gastrointestinal stromal tumor (GIST): Pediatric wild-type (WT) GIST: diagnosed at a young
age (< 18) or having characteristics consistent with Carney triad of Carney-Stretakis
syndrome vs Adult WT GIST: all others.

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.

Patients undergo blood sample collection at baseline and periodically during treatment for
biomarker studies. Tumor tissue samples from biopsy or time of relapse may also be collected
for correlative studies.

After completion of study treatment, patients are followed up for 30 days, every 12 weeks
for 2 years (from date of first dose of linsitinib), and then annually thereafter.

Inclusion Criteria


- 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


- 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

- 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

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

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

- 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


- 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

Type of Study:


Study Design:

Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Response rate (CR or PR) at 6 months

Safety Issue:


Principal Investigator

Margaret von Mehren, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Fox Chase Cancer Center


United States: Food and Drug Administration

Study ID:




Start Date:

March 2012

Completion Date:

Related Keywords:

  • Carney Complex
  • Gastrointestinal Stromal Tumor
  • Paraganglioma
  • Sarcoma
  • gastrointestinal stromal tumor
  • chondrosarcoma
  • paraganglioma
  • Carney complex
  • Paraganglioma
  • Gastrointestinal Stromal Tumors
  • Carney Complex
  • Sarcoma



University of Michigan Comprehensive Cancer Center Ann Arbor, Michigan  48109-0752
Fox Chase Cancer Center - Philadelphia Philadelphia, Pennsylvania  19111-2497
Oregon Health and Science University Portland, Oregon  97201
Stanford Comprehensive Cancer Center Stanford, California  94305
Dana Farber Boston, Massachusetts  02115-6084