Phase 2 trial of dasatinib in target-selected patients with recurrent glioblastoma (RTOG 0627)

Neuro-oncology
Andrew B LassmanMinesh P Mehta

Abstract

We conducted a phase II trial to evaluate the efficacy of dasatinib, a multitargeted tyrosine kinase inhibitor, for adults with recurrent glioblastoma (GBM). Eligibility requirements were Karnofsky performance status ≥ 60%; no concurrent hepatic enzyme-inducing anticonvulsants; prior treatment with surgery, radiotherapy, and temozolomide exclusively; and activation or overexpression of ≥ 2 putative dasatinib targets in GBM (ie, SRC, c-KIT, EPHA2, and PDGFR). Using a 2-stage design, 77 eligible participants (27 in stage 1, if favorable, and then 50 in stage 2) were needed to detect an absolute improvement in the proportion of patients either alive and progression-free patients at 6 months (6mPFS) or responding (any duration) from a historical 11% to 25%. A high rate of ineligibility (27%) to stage 1 precluded a powered assessment of efficacy, but there was also infrequent treatment-related toxicity at 100 mg twice daily. Therefore, the study was redesigned to allow intrapatient escalation by 50 mg daily every cycle as tolerated (stage 1B) before determining whether to proceed to stage 2. Escalation was tolerable in 10 of 17 (59%) participants evaluable for that endpoint; however, among all eligible patients (stages 1 and 1B, n =...Continue Reading

References

Jul 1, 1990·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·D R MacdonaldJ G Cairncross
Mar 1, 1989·Controlled Clinical Trials·R Simon
Feb 7, 1997·Cell·T Hunter
Nov 24, 1999·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·E T WongW K Yung
Mar 11, 2005·The New England Journal of Medicine·Roger StuppUNKNOWN National Cancer Institute of Canada Clinical Trials Group
Oct 29, 2005·Molecular Cancer Research : MCR·Jill WykoskyWaldemar Debinski
Nov 12, 2005·The New England Journal of Medicine·Ingo K MellinghoffPaul S Mischel
Jul 28, 2006·Cold Spring Harbor Symposia on Quantitative Biology·C L Sawyers
Aug 18, 2006·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Patrick Y WenMichael D Prados
Mar 22, 2008·Neuro-oncology·Kathleen R LambornUNKNOWN North American Brain Tumor Consortium
Oct 1, 2008·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Eric RaymondUNKNOWN European Organisation for Research and Treatment of Cancer Brain Tumor Group Study
Dec 31, 2008·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Teri N KreislHoward A Fine
Sep 2, 2009·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Henry S FriedmanTimothy Cloughesy
Oct 1, 2009·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·George D DemetriT R Jeffry Evans
Oct 16, 2010·Cancer Letters·Manmeet S AhluwaliaCandece L Gladson
Mar 13, 2012·Journal of Neuro-oncology·David A ReardonHenry S Friedman
Jun 1, 2012·Science Translational Medicine·Banibrata SenFaye M Johnson
Aug 13, 2013·Lung Cancer : Journal of the International Association for the Study of Lung Cancer·Vincenzo PitiniGiuseppe Altavilla
Feb 21, 2014·The New England Journal of Medicine·Mark R GilbertMinesh P Mehta
Feb 21, 2014·The New England Journal of Medicine·Olivier L ChinotTimothy Cloughesy

❮ Previous
Next ❯

Citations

Feb 3, 2016·Critical Reviews in Oncology/hematology·Katharina SeystahlMichael Weller
Jun 7, 2015·Annals of Hematology·Bronagh McCabeKen I Mills
Nov 21, 2014·Journal of Neuro-oncology·Jennie W TaylorAndrew S Chi
May 14, 2016·Expert Opinion on Investigational Drugs·Verena StaedtkeJohn Laterra
Oct 16, 2015·Neuro-oncology·Wolfgang WickFrank Winkler
Mar 2, 2016·Therapeutic Advances in Medical Oncology·Robert E HurstMichael A Ihnat
Dec 19, 2017·Journal of Drug Targeting·Khaled GreishHayley Nehoff
Dec 16, 2017·CNS Oncology·Hao-Wen SimWarren P Mason
Nov 14, 2019·Current Topics in Medicinal Chemistry·Vadim V TarasovGjumrakch Aliev
Sep 2, 2016·Oncotarget·Carl KoschmannMaria G Castro
Jan 13, 2017·Topics in Magnetic Resonance Imaging : TMRI·Rebecca A Harrison, John F de Groot
Mar 22, 2019·Journal of Translational Medicine·Niklas SchäferMartin Glas
May 19, 2019·Current Oncology Reports·Ding Fang Chuang, Xuling Lin
May 21, 2019·Expert Review of Neurotherapeutics·Candice D CarpenterVinay K Puduvalli
Jul 1, 2020·The Journal of Clinical Investigation·Zachary MikljaCarl Koschmann
Aug 1, 2020·Nature Communications·Weihua ZhouDaniel R Wahl
Jun 4, 2020·International Journal of Molecular Sciences·Filippo TorrisiSamuel Valable
Apr 3, 2020·Archives of Pharmacal Research·Gayoung Kim, Young Tag Ko
Jul 7, 2020·Neuro-oncology Practice·Shehryar SheikhMichael Vogelbaum
Jun 18, 2020·Cancers·Claudia CirottiDaniela Barilà
Sep 25, 2017·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Tony AvrilVéronique Quillien
Sep 14, 2019·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Rupa JuthaniCameron W Brennan
Jan 6, 2021·International Journal of Molecular Sciences·Alexander OuNazanin Majd
Dec 21, 2020·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Maha Al-AsmakhAla-Eddin Al Moustafa
Nov 17, 2020·Frontiers in Immunology·Deling LiZhen Cheng
Dec 31, 2020·Cancers·Cristina BirzuGiuseppe Lombardi
Jan 8, 2017·Biomaterials·Leoni A Kunz-SchughartSuman Pokhrel
Apr 23, 2021·Pathology, Research and Practice·Enrico FranceschiAlba Ariela Brandes
May 1, 2021·Cancers·Elisabete Cruz Da SilvaLaurence Choulier
Nov 3, 2016·Journal of Nuclear Medicine : Official Publication, Society of Nuclear Medicine·Katja BehlingMichael R McDevitt
Sep 3, 2017·Annals of Oncology : Official Journal of the European Society for Medical Oncology·M TouatK L Ligon
Jul 25, 2021·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Wei WuHeike E Daldrup-Link
Jul 11, 2020·Cancer Cell·Zilai WangLuis F Parada

❮ Previous
Next ❯

Related Concepts

Related Feeds

Cancer Stem Cells in Glioblastoma

Glioblastoma is the most common and aggressive type of brain tumor. It contains a population of tumor initiating stem cell-like cells known as cancer stem cells. Investigations are ongoing into these cancer stem cells found in these solid tumors which are highly resistance to treatment. Here is the latest research on cancer stem cells in glioblastoma.