2017
A Phase I–II Study of the Oral PARP Inhibitor Rucaparib in Patients with Germline BRCA1/2-Mutated Ovarian Carcinoma or Other Solid Tumors
Kristeleit R, Shapiro GI, Burris HA, Oza AM, LoRusso P, Patel MR, Domchek SM, Balmaña J, Drew Y, Chen LM, Safra T, Montes A, Giordano H, Maloney L, Goble S, Isaacson J, Xiao J, Borrow J, Rolfe L, Shapira-Frommer R. A Phase I–II Study of the Oral PARP Inhibitor Rucaparib in Patients with Germline BRCA1/2-Mutated Ovarian Carcinoma or Other Solid Tumors. Clinical Cancer Research 2017, 23: 4095-4106. PMID: 28264872, DOI: 10.1158/1078-0432.ccr-16-2796.Peer-Reviewed Original ResearchConceptsHigh-grade ovarian carcinomaObjective response rateInvestigator-assessed objective response rateOral rucaparibAdverse eventsCommon treatment-emergent adverse eventsTreatment-emergent adverse eventsAspartate transaminase elevationsAsthenia/fatigueProtocol-defined criteriaRECIST version 1.1Phase II doseAdvanced solid tumorsProgression-free intervalSmall molecule PARP inhibitorsClin Cancer ResManageable toxicityPrior regimensPrimary endpointTransaminase elevationPlatinum therapyMultiple dosesOvarian carcinomaAlanine transaminaseClinical activity
2014
882PD Phase 1/2 Study of Oral Rucaparib: Updated Phase 1 and Preliminary Phase 2 Results
Kristeleit R, Shapira-Frommer R, Burris H, Patel M, Lorusso P, Oza A, Balmaña J, Domchek S, Chen L, Montes A, Plummer R, Arkenau H, Maloney L, Dominy E, Shapiro G. 882PD Phase 1/2 Study of Oral Rucaparib: Updated Phase 1 and Preliminary Phase 2 Results. Annals Of Oncology 2014, 25: iv307. DOI: 10.1093/annonc/mdu338.8.Peer-Reviewed Original ResearchAdvanced solid tumorsDurable benefitSolid tumorsDana-Farber Cancer InstituteHighest LOHCA-125 responsePhase 1/2 studyDose-escalation designPhase 1Homologous recombination-deficient tumorsOral PARP inhibitorClinical trial fundingPhase 2CA125 responseCommon AEsOral rucaparibRelapsed diseaseLow HgbEscalation designLow plateletsClinical benefitLab abnormalitiesBRCA mutationsPancreatic cancerClinical trials
2013
A phase I dose-escalation and PK study of continuous oral rucaparib in patients with advanced solid tumors.
Kristeleit R, Shapiro G, LoRusso P, Infante J, Flynn M, Patel M, Tolaney S, Hilton J, Calvert A, Giordano H, Isaacson J, Borrow J, Allen A, Jaw-Tsai S, Burris H. A phase I dose-escalation and PK study of continuous oral rucaparib in patients with advanced solid tumors. Journal Of Clinical Oncology 2013, 31: 2585-2585. DOI: 10.1200/jco.2013.31.15_suppl.2585.Peer-Reviewed Original ResearchAdvanced solid tumorsOral rucaparibStable diseaseTrough levelsSolid tumorsIntra-patient dose escalationOverall disease control rateTreatment-related adverse eventsOral small-molecule inhibitorDose-proportional PKDurable stable diseaseLow interpatient variabilityPhase 2 doseDisease control rateDose-escalation designDose cohortsBID dosingAdverse eventsObjective responsePK assessmentDose escalationEscalation designControl rateQD dosingStandard treatment