Linsitinib in Treating Patients With Gastrointestinal Stromal Tumors

NCT01560260 | Completed Phase 2 Results

• 6 other identifiers: NCI-2012-00708CDR0000728619SARC-022SARC 022SARC0228945
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 8

Brief Summary

This phase II trial studies how well linsitinib works in treating younger and adult patients with gastrointestinal stromal tumors. Linsitinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

Conditions

Carney Complex; Chondrosarcoma; Gastrointestinal Stromal Tumor; Paraganglioma

Outcome Measures

Primary Outcomes (1)

• Number of Participants With Complete Response or Partial Response Using Response Evaluation Criteria in Solid Tumors Guideline Version 1.1

  Determine the response rate, Complete Response (CR) or Partial Response (PR), to treatment with linsitinib (OSI-906) in patients with advanced wild-type (WT) gastrointestional stromal tumor (GIST) as determined by RECIST 1.1.

  At 6 months

Secondary Outcomes (10)

• Clinical Benefit Rate Defined as Stable Disease (SD) >= 9 Months, Partial Response (PR) or Complete Response (CR)

  Up to 2 years

• Overall Survival (OS)

  Estimates at 9 months

• Progression Free Survival (PFS)

  Time from date of enrollment to time of progression or death due to any cause, estimates at 9 months

• Response Duration

  Up to 37 weeks

• Failure-free Survival

  Up to 37 weeks

Other Outcomes (2)

• Time to Progression

  Up to 3 years

• Determine the Number of Participants With Tumor Metabolic Response Correlating With Anatomic Response and Clinical Benefit.

  Up to 37 weeks

Study Arms (1)

Treatment (linsitinib)

EXPERIMENTAL

Patients receive linsitinib 150mg orally (PO) twice daily (BID) on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Other: Laboratory Biomarker Analysis; Drug: Linsitinib; Other: Pharmacological Study

Interventions

Laboratory Biomarker Analysis OTHER

Correlative studies

Treatment (linsitinib)

Linsitinib DRUG

Given PO

Also known as: IGF-1R inhibitor OSI-906, OSI-906, OSI-906AA

Treatment (linsitinib)

Pharmacological Study OTHER

Correlative studies

Treatment (linsitinib)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients must have histologically confirmed gastrointestinal stromal tumor (GIST) with confirmed genotype of wild-type in a Clinical Laboratory Improvement Amendments (CLIA) certified laboratory
• Patients will be stratified into pediatric and adult cohorts; patients in the 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 and have had progression on or intolerance to progression on therapy; patients in the adult cohort (age at diagnosis \> 18 years AND no diagnosis of diagnosis of Carney Triad or Carney-Stratakis Diad) have had progression on or intolerance to imatinib therapy as documented by treating physician
• Performance status: Eastern Cooperative Oncology Group (ECOG) 0-2
• Patients must have measurable disease defined as lesions that can be measured in 2 dimensions by medical imaging techniques such as CT or magnetic resonance imaging (MRI); ascites, pleural fluid, and lesions seen on PET scan only are not considered measurable
• White blood cells count (WBC) \>= 2.0 x 10\^9/L (being \>= 14 days off growth factors) OR
• Absolute neutrophil count (ANC) \>= 1.5 x 10\^9/L (being \>= 14 days off growth factors)
• Platelet count \>= 75 x 10\^9/L
• Total bilirubin =\< 1.5 times the upper limit of normal for age
• Alanine aminotransferase (ALT)/aspartate aminotransferase (AST) (serum glutamate pyruvate transaminase \[SGPT\]/serum glutamic oxaloacetic transaminase \[SGOT\]) =\< 3 x the upper limit of normal (ULN) for the reference lab (=\< 5 x the ULN for the reference lab in the presence of known hepatic metastasis, adjusted for age)
• Creatinine clearance \> 70 ml/min/1.73m\^2 or
• Serum creatinine \< 1.5 x ULN per age and gender
• QT interval corrected using Frederica formula (QTcF) interval average of \< 450 msec at baseline using the Frederica formula (QTcF)
• No concomitant drugs that prolong the QT corrected (QTc) interval
• No significant cardiac disease
• Fasting blood glucose \< 150 mg/dL at baseline

You may not qualify if:

• 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
• Patients who are receiving any other investigational agents or other anti-cancer therapies other than those administered in this study during protocol treatment
• Patients with diabetes mellitus requiring insulin for control of their diabetes
• Patients with a history of liver cirrhosis
• Patients with known brain metastases should be excluded from this clinical trial
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to linsitinib (OSI-906)
• While cytochrome P450 1A2 (CYP1A2) inhibitors/inducers are not specifically excluded, investigators should be aware that linsitinib (OSI 906) exposure may be altered by the concomitant administration of these drugs
• While cytochrome P450 2C9 (CYP2C9) substrates are not specifically excluded, investigators should be aware that levels of drugs metabolized by CYP2C9 may be increased by the concomitant administration of linsitinib (OSI-906); caution should be used when administering CYP2C9 substrates to patients who are on study drug
• Use of the potent CYP1A2 inhibitors ciprofloxacin and fluvoxamine are prohibited; other less potent CYP1A2 inhibitors/inducers are not excluded
• 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
• Prior treatment with another kinase inhibitor targeting insulin-like growth factor 1 receptor (IGF-1R) pathway, including monoclonal antibodies targeting IGF-1R
• Pregnant women are excluded from this study; breastfeeding should be discontinued if the mother is treated with linsitinib (OSI-906)
• 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 or urine) within the 7 days prior to study drug administration
• NOTE: Women of childbearing potential include both pre-menopausal women and women within the first 2 years of the onset of menopause
• NOTE: Effective methods of birth control includes: surgically sterile, barrier device (condom, diaphragm), contraceptive coil, abstinence; oral contraceptive pills (OCPs) alone are not considered an effective method

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (8)

Stanford Cancer Institute

Palo Alto, California, 94304, United States

Location

University of Iowa/Holden Comprehensive Cancer Center

Iowa City, Iowa, 52242, United States

Location

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States

Location

Dana-Farber/Harvard Cancer Center

Boston, Massachusetts, 02115, United States

Location

Sarcoma Alliance for Research Through Collaboration

Ann Arbor, Michigan, 48106, United States

Location

University of Michigan Comprehensive Cancer Center

Ann Arbor, Michigan, 48109, United States

Location

Oregon Health and Science University

Portland, Oregon, 97239, United States

Location

Fox Chase Cancer Center

Philadelphia, Pennsylvania, 19111, United States

Location

Related Publications (1)

• Songdej N, von Mehren M. GIST treatment options after tyrosine kinase inhibitors. Curr Treat Options Oncol. 2014 Sep;15(3):493-506. doi: 10.1007/s11864-014-0295-3.

  PMID: 24952730 DERIVED

MeSH Terms

Conditions

Carney Complex; Chondrosarcoma; Gastrointestinal Stromal Tumors; Paraganglioma

Interventions

3-(8-amino-1-(2-phenylquinolin-7-yl)imidazo(1,5-a)pyrazin-3-yl)-1-methylcyclobutanol

Condition Hierarchy (Ancestors)

Myxoma; Neoplasms, Connective Tissue; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Heart Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Heart Diseases; Cardiovascular Diseases; Abnormalities, Multiple; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Skin Abnormalities; Sarcoma; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue

Results Point of Contact

• Title: Kristen Nuyen, Research Project Manager
• Organization: Sarcoma Alliance for Research through Collaboration (SARC)

sarc@sarctrials.org

734-930-7600

Study Officials

• Margaret von Mehren

  Sarcoma Alliance for Research through Collaboration

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 20, 2012
• First Posted: March 22, 2012
• Study Start: March 1, 2012
• Primary Completion: October 1, 2015
• Study Completion: October 1, 2015
• Last Updated: September 21, 2018
• Results First Posted: January 19, 2017

Record last verified: 2018-08

Locations

US (8)