A phase 2 study of OSI-906 (linsitinib, an insulin-like growth factor receptor-1 inhibitor) in patients with asymptomatic or mildly symptomatic (non-opioid requiring) metastatic castrate resistant prostate cancer (CRPC)

Investigational New Drugs
Pedro BarataJorge A Garcia

Abstract

Background The inhibition of insulin-like growth factor receptor-1 (IGF-1R) induces cell cycle arrest and enhancing the effect of castration by delay of progression of human prostate cancer models. Linsitinib is a small molecule and potent dual inhibitor of IGF-1R and insulin receptor tyrosine kinase activity. We report results of a single-arm, phase II study evaluating the safety and efficacy of linsitinib in men with chemotherapy-naïve asymptomatic or mildly symptomatic metastatic castration resistant prostate cancer (mCRPC). Methods Patients received at 150 mg orally twice daily on a 28-day cycle. The primary endpoint was prostate specific (PSA) response at 12 weeks and correlative studies included circulating tumor cells (CTCs) and circulating endothelial cells (CECs). Results Seventeen patients, median age 68 (55-78) and pre-treatment PSA of 55.23 (2.46-277.60) were enrolled and completed 12 weeks of therapy. All but two patients discontinued therapy secondary to PSA progression, which met the predefined futility criteria and led to early termination of this study. Overall best response (RECIST v1.1) included a partial response in 1 patient and stable disease in 8 patients. Higher baseline CTCs were associated with higher ...Continue Reading

References

Apr 1, 1993·British Journal of Cancer·J B SørensenH H Hansen
Jul 18, 2002·Journal of the National Cancer Institute·June M ChanEdward Giovannucci
Apr 24, 2003·JAMA : the Journal of the American Medical Association·Sana M Al-KhatibRobert M Califf
Jul 2, 2004·Nature Reviews. Cancer·Michael N PollakSusan E Hankinson
Jul 18, 2006·Biochimica Et Biophysica Acta·Raushan T Kurmasheva, Peter J Houghton
Aug 26, 2006·Endocrine Reviews·Amir Abbas SamaniPnina Brodt
Oct 26, 2006·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Jennifer D WuStephen R Plymate
Oct 3, 2007·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Paul HaluskaJohann S de Bono
Mar 4, 2008·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Howard I ScherUNKNOWN Prostate Cancer Clinical Trials Working Group
Aug 1, 2008·Endocrine-related Cancer·Meng-Lei Zhu, Natasha Kyprianou
Aug 13, 2008·Annals of Oncology : Official Journal of the European Society for Medical Oncology·D OlmosJ S de Bono
Oct 3, 2008·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Johann S de BonoDerek Raghavan
Nov 26, 2008·Nature Reviews. Cancer·Michael Pollak
Dec 23, 2008·European Journal of Cancer : Official Journal for European Organization for Research and Treatment of Cancer (EORTC) [and] European Association for Cancer Research (EACR)·E A EisenhauerJ Verweij
Feb 3, 2009·International Journal of Urology : Official Journal of the Japanese Urological Association·Satoko KojimaYuzo Furuya
Aug 24, 2011·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Howard I ScherGlenn Heller
Apr 16, 2013·European Urology·Arnoud J TempletonUNKNOWN Swiss Group for Clinical Cancer Research (SAKK)
Jun 3, 2014·The New England Journal of Medicine·Tomasz M BeerUNKNOWN PREVAIL Investigators
Sep 12, 2014·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Robin L JonesCraig P Carden
Sep 13, 2014·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Igor PuzanovT R Jeffry Evans
Apr 8, 2015·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Evan Y YuIan M Thompson
Oct 29, 2015·The New England Journal of Medicine·Joaquin MateoJohann S de Bono
Jan 6, 2017·CA: a Cancer Journal for Clinicians·Rebecca L SiegelAhmedin Jemal
Aug 10, 2017·Oncology Letters·Weiwei LiuZhihua Tao

❮ Previous
Next ❯

Citations

Aug 28, 2020·Signal Transduction and Targeted Therapy·Qing WangHsin-Sheng Yang
Feb 1, 2019·Signal Transduction and Targeted Therapy·Jihao XuChing-Hsien Chen
Aug 17, 2019·Cells·Eliot Osher, Valentine M Macaulay
Dec 3, 2020·Cancers·Stefanie de GrootJudith R Kroep
Jan 9, 2021·Cancer Research·Francesco TamiroVincenzo Giambra

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.