0000000000083494

AUTHOR

Steven J. Isakoff

showing 5 related works from this author

Multicenter Phase II Study of Lurbinectedin in BRCA-Mutated and Unselected Metastatic Advanced Breast Cancer and Biomarker Assessment Substudy

2018

Purpose This multicenter phase II trial evaluated lurbinectedin (PM01183), a selective inhibitor of active transcription of protein-coding genes, in patients with metastatic breast cancer. A unicenter translational substudy assessed potential mechanisms of lurbinectedin resistance. Patients and Methods Two arms were evaluated according to germline BRCA1/2 status: BRCA1/2 mutated (arm A; n = 54) and unselected ( BRCA1/2 wild-type or unknown status; arm B; n = 35). Lurbinectedin starting dose was a 7-mg flat dose and later, 3.5 mg/m2 in arm A. The primary end point was objective response rate (ORR) per Response Evaluation Criteria in Solid Tumors (RECIST). The translational substudy of resist…

Adult0301 basic medicineOncologyCancer Researchmedicine.medical_specialtyGenes BRCA2Genes BRCA1Phases of clinical researchAntineoplastic AgentsBreast NeoplasmsHeterocyclic Compounds 4 or More RingsMice03 medical and health sciences0302 clinical medicineGermline mutationInternal medicineBiomarkers TumorClinical endpointAnimalsHumansMedicineProgression-free survivalGerm-Line MutationAgedDose-Response Relationship DrugErratabusiness.industryMiddle Agedmedicine.diseaseXenograft Model Antitumor AssaysMetastatic breast cancerProgression-Free SurvivalClinical trial030104 developmental biologyOncologyResponse Evaluation Criteria in Solid Tumors030220 oncology & carcinogenesisBiomarker (medicine)FemalebusinessCarbolinesJournal of Clinical Oncology
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PI3K/AKT Activation and Response in Phase IB: AKT Inhibitor GDC-0068 with Docetaxel (D) Or MFOLFOX6 (F) in Refractory Solid Tumors

2013

R. Meng1, L. R. Molife2, L. de Mattos-Arruda3, A. Hollebecque4, S. J. Isakoff5, D. Roda6, Y. Yan1, A. Cervantes6, J. C. Soria4, J. Mateo2, G. Argiles3, J. C. Bendell7 Genentech, South San Francisco, CA, USA, Institute of Cancer Research/ Royal Marsden Hospital, Sutton, United Kingdom, Vall d’Hebron University Hospital, Barcelona, Spain, Institut Gustave Roussy, Villejuif, France, Massachusetts General Hospital, Boston, MA, USA, Institute of Health Research INCLIVA, University of Valenica, Valencia, Spain, Sarah Cannon Research Institute, Nashville, TN, USA

OncologySolid tumourmedicine.medical_specialtybusiness.industryHematologyAkt inhibitorUniversity hospitalInstitut Gustave RoussyOncologyDocetaxelInternal medicinemedicineGeneral hospitalbusinessProtein kinase BPI3K/AKT/mTOR pathwaymedicine.drugAnnals of Oncology
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Antitumor activity of ipatasertib combined with chemotherapy: results from a phase Ib study in solid tumors

2020

Inhibidor d'AKT; Càncer avançat; Fase I Inhibidor de AKT; Cáncer avanzado; Fase I AKT inhibitor; Advanced cancer; Phase I Background This phase Ib study evaluated the safety, tolerability, pharmacokinetics, and preliminary efficacy of the oral AKT inhibitor ipatasertib and chemotherapy or hormonal therapy in patients with advanced or metastatic solid tumors to determine combined dose-limiting toxicities (DLTs), maximum tolerated dose, and recommended phase II doses and schedules. Patients and methods The clinical study comprised four combination treatment arms: arm A (with docetaxel), arm B [with mFOLFOX6 (modified leucovorin, 5-fluorouracil, and oxaliplatin)], arm C (with paclitaxel), and …

Male0301 basic medicinemedicine.medical_specialtyMaximum Tolerated Dosemedicine.medical_treatmentCàncer - Quimioteràpia:Otros calificadores::Otros calificadores::/efectos adversos [Otros calificadores]GastroenterologyAKT inhibitorPiperazinesMedicaments antineoplàstics - Efectes secundaris:neoplasias [ENFERMEDADES]03 medical and health scienceschemistry.chemical_compound0302 clinical medicineNeoplasmsInternal medicineAntineoplastic Combined Chemotherapy Protocols:Other subheadings::Other subheadings::/adverse effects [Other subheadings]medicineadvanced cancerHumansEnzalutamide:terapéutica::protocolos clínicos::protocolos antineoplásicos::protocolos de quimioterapia antineoplásica combinada [TÉCNICAS Y EQUIPOS ANALÍTICOS DIAGNÓSTICOS Y TERAPÉUTICOS]Adverse effectChemotherapybusiness.industryHematologyphase I:Therapeutics::Clinical Protocols::Antineoplastic Protocols::Antineoplastic Combined Chemotherapy Protocols [ANALYTICAL DIAGNOSTIC AND THERAPEUTIC TECHNIQUES AND EQUIPMENT]Oxaliplatin:Neoplasms [DISEASES]Pyrimidines030104 developmental biologyOncologyDocetaxelTolerabilityPaclitaxelchemistryResponse Evaluation Criteria in Solid Tumors030220 oncology & carcinogenesisbusinessmedicine.drugAnnals of Oncology
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A phase Ib study of the Akt inhibitor GDC-0068 with docetaxel (D) or mFOLFOX-6 (F) in patients (pts) with advanced solid tumors.

2012

3021 Background: Activation of the Akt pathway is observed in multiple tumors and may contribute to chemoresistance. GDC-0068 is an ATP-competitive small molecule inhibitor of all three isoforms of Akt; in a phase Ia study, it was well tolerated with maximum tolerated dose (MTD) of 600 mg daily (21 days on/7days off) and pharmacodynamic down-regulation of Akt signaling in tumors at doses ≥100 mg. In vitro, GDC-0068 shows synergism with cytotoxic agents. This phase Ib study defines the dose limiting toxicities (DLT), MTD, safety and pharmacokinetics (PK) of GDC0068 in combination with D and F. Methods: Using a 3+3 designeligible patients (pt) with advanced/metastatic solid tumors were treat…

Gene isoformCancer Researchbusiness.industryAkt inhibitorSmall moleculeOncologyDocetaxelmedicineCancer researchIn patientMultiple tumorsbusinessPI3K/AKT/mTOR pathwaymedicine.drugJournal of Clinical Oncology
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Abstract P6-12-02: Phase Ib dose-escalation study of an Akt inhibitor ipatasertib (Ipat) in combination with docetaxel (Doc) or paclitaxel (Pac) in p…

2015

Abstract Background: The Akt pathway is frequently aberrantly activated in MBC (e.g. via PTEN loss, and/or alterations of PIK3CA, AKT1, or AKT3); additionally, Akt activation may occur in response to chemotherapy, leading to cell survival and chemoresistance. Ipat (GDC-0068) is a potent oral, ATP-competitive inhibitor of all Akt isoforms. In preclinical models, Ipat synergistically combined with taxanes. In the Phase I dose-escalation single agent study, Ipat was given to pts including MBC, and downregulated Akt signaling at doses ≥ 100 mg. Methods: Eligible pts with MBC, treated with up to 3 prior systemic chemotherapy regimens, received Doc 75 mg/m2 intravenously (IV) on Day 1 with escala…

OncologyCancer ResearchChemotherapymedicine.medical_specialtybiologybusiness.industrymedicine.medical_treatmentCancermedicine.diseaseIpatasertibMetastatic breast cancerchemistry.chemical_compoundEndocrinologyBreast cancerOncologyDocetaxelPaclitaxelchemistryInternal medicinemedicinebiology.proteinPTENbusinessmedicine.drugCancer Research
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