2016
Phase I study of pemetrexed with sorafenib in advanced solid tumors
Poklepovic A, Gordon S, Shafer DA, Roberts JD, Bose P, Geyer CE, McGuire WP, Tombes MB, Shrader E, Strickler K, Quigley M, Wan W, Kmieciak M, Massey HD, Booth L, Moran RG, Dent P. Phase I study of pemetrexed with sorafenib in advanced solid tumors. Oncotarget 2016, 7: 42625-42638. PMID: 27213589, PMCID: PMC5173162, DOI: 10.18632/oncotarget.9434.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAntineoplastic AgentsAntineoplastic Combined Chemotherapy ProtocolsBiomarkers, TumorCohort StudiesFemaleHumansInflammationMaleMaximum Tolerated DoseMiddle AgedNeoplasmsNiacinamidePemetrexedPhenylurea CompoundsPTEN PhosphohydrolaseSorafenibTreatment OutcomeTriple Negative Breast NeoplasmsConceptsAdvanced solid tumorsDay 1Solid tumorsOral sorafenibDose scheduleBreast cancerTriple-negative breast cancerDose-escalation schemaPhase II dosePhase I trialSorafenib dosingSorafenib therapyStable diseaseCohort BComplete responseI trialPartial responseTolerable combinationRadiographic assessmentCumulative toxicityCombination treatmentPatientsSorafenibPhase IAntitumor activityA phase I study of indoximod in patients with advanced malignancies
Soliman HH, Minton SE, Han HS, Ismail-Khan R, Neuger A, Khambati F, Noyes D, Lush R, Chiappori AA, Roberts JD, Link C, Vahanian NN, Mautino M, Streicher H, Sullivan DM, Antonia SJ. A phase I study of indoximod in patients with advanced malignancies. Oncotarget 2016, 7: 22928-22938. PMID: 27008709, PMCID: PMC5008412, DOI: 10.18632/oncotarget.8216.Peer-Reviewed Original ResearchConceptsStable diseaseDose levelsC-reactive protein levelsReactive protein levelsAdvanced solid tumorsTumor-mediated immunosuppressionPhase I trialUntreated brain metastasesMetastatic solid malignanciesMultiple dose levelsAntigen autoantibodiesBrain metastasesCheckpoint inhibitorsImmune correlatesPrimary endpointSecondary endpointsAdvanced malignanciesCRP levelsI trialOral inhibitorAutoimmune diseasesMarrow functionSolid malignanciesInclusion criteriaExclusion criteria
2011
Phase II Trials Powered to Detect Tumor Subtypes
Roberts JD, Ramakrishnan V. Phase II Trials Powered to Detect Tumor Subtypes. Clinical Cancer Research 2011, 17: 5538-5545. PMID: 21737510, DOI: 10.1158/1078-0432.ccr-10-2466.Peer-Reviewed Original ResearchConceptsTumor subtypesResponse ratePhase II trial designPhase II trialPhase III trialsOverall response ratePhase II designStage 1Characterization of tumorsII trialIII trialsMetastatic diseaseSimilar patientsProspective characterizationSample sizeTrial designSubtypesTumorsTotal sample sizePhase IIII designTrialsTreatmentVariables of interestDifferent treatments
2010
A phase I pharmacokinetic study of pulse-dose vorinostat with flavopiridol in solid tumors
Dickson MA, Rathkopf DE, Carvajal RD, Grant S, Roberts JD, Reid JM, Ames MM, McGovern RM, Lefkowitz RA, Gonen M, Cane LM, Dials HJ, Schwartz GK. A phase I pharmacokinetic study of pulse-dose vorinostat with flavopiridol in solid tumors. Investigational New Drugs 2010, 29: 1004-1012. PMID: 20461440, PMCID: PMC3545439, DOI: 10.1007/s10637-010-9447-x.Peer-Reviewed Original ResearchConceptsSerum levelsPhase I pharmacokinetic studyIntermittent high doseResults 34 patientsD1-3I pharmacokinetic studyCyclin-dependent kinase inhibitor flavopiridolKinase inhibitor flavopiridolStable diseaseOral doseOral dosingHigh doseCombination treatmentPatientsSolid tumorsCmaxOne weekDosePharmacokinetic studyVorinostatMTDFlavopiridolNeutropeniaChemotherapyLevels
2009
Phase I study of bryostatin 1, a protein kinase C modulator, preceding cisplatin in patients with refractory non-hematologic tumors
Pavlick AC, Wu J, Roberts J, Rosenthal MA, Hamilton A, Wadler S, Farrell K, Carr M, Fry D, Murgo AJ, Oratz R, Hochster H, Liebes L, Muggia F. Phase I study of bryostatin 1, a protein kinase C modulator, preceding cisplatin in patients with refractory non-hematologic tumors. Cancer Chemotherapy And Pharmacology 2009, 64: 803. PMID: 19221754, PMCID: PMC3901370, DOI: 10.1007/s00280-009-0931-y.Peer-Reviewed Original ResearchConceptsPeripheral blood mononuclear cellsPhase INon-hematologic tumorsPhase II dosesPhase II doseDose-limiting toxicityResultsFifty-three patientsBlood mononuclear cellsNon-hematologic malignanciesBryostatin 1Cytotoxicity of cisplatinCisplatin 50PurposePreclinical dataObjective responseContinuous infusionMononuclear cellsTolerable dosesProtein kinase C modulatorsCisplatin effectComputerized tomographyPatientsConsistent inhibitionCisplatin cytotoxicityCisplatinMinimal toxicity
2008
Vorinostat and Sorafenib Synergistically Kill Tumor Cells via FLIP Suppression and CD95 Activation
Zhang G, Park MA, Mitchell C, Hamed H, Rahmani M, Martin AP, Curiel DT, Yacoub A, Graf M, Lee R, Roberts JD, Fisher PB, Grant S, Dent P. Vorinostat and Sorafenib Synergistically Kill Tumor Cells via FLIP Suppression and CD95 Activation. Clinical Cancer Research 2008, 14: 5385-5399. PMID: 18765530, PMCID: PMC2561272, DOI: 10.1158/1078-0432.ccr-08-0469.Peer-Reviewed Original ResearchConceptsPancreatic adenocarcinoma cellsLong-term colony formation assaysCaspase-8C-FLIPExtracellular signal-regulated kinase 1/2Full-length BidSignal-regulated kinase 1/2Activation of BaxKnockdown of CD95Multiple antiapoptotic proteinsExpression of BimColony formation assaysAdenocarcinoma cellsVorinostat treatmentCD95 activationKill Tumor CellsProapoptotic signalsProtease pathwayKinase 1/2Caspase-9Cathepsin proteasesAntiapoptotic proteinsBcl-xLFADD expressionMcl-1
2003
Phase I studies of weekly administration of cytotoxic agents: Implications of a mathematical model
McClish DK, Roberts JD. Phase I studies of weekly administration of cytotoxic agents: Implications of a mathematical model. Investigational New Drugs 2003, 21: 299-308. PMID: 14578680, DOI: 10.1023/a:1025464510639.Peer-Reviewed Original ResearchThe use of cyclin-dependent kinase inhibitors alone or in combination with established cytotoxic drugs in cancer chemotherapy
Grant S, Roberts JD. The use of cyclin-dependent kinase inhibitors alone or in combination with established cytotoxic drugs in cancer chemotherapy. Drug Resistance Updates 2003, 6: 15-26. PMID: 12654284, DOI: 10.1016/s1368-7646(02)00141-3.Peer-Reviewed Original ResearchConceptsCyclin-dependent kinase inhibitorCytotoxic agentsKinase inhibitorsSingle-agent activityCDK inhibitorsConventional cytotoxic agentsAnti-tumor effectsApoptotic regulatory moleculesCell cycle dysregulationNeoplastic cell proliferationAbundant preclinical evidencePreclinical evidenceTumor cell typesCritical molecular targetsClinical studiesSpecific tumor cell typesPreclinical studiesClinical developmentSmall molecule inhibitorsCell cycle traverseCytotoxic drugsAntitumor efficacyClinical arenaCancer chemotherapyMolecular targets
2001
Adoptive immunotherapy of cancer with pharmacologically activated lymph node lymphocytes: a pilot clinical trial
Bear H, Roberts J, Cornell D, Tombes M, Kyle B. Adoptive immunotherapy of cancer with pharmacologically activated lymph node lymphocytes: a pilot clinical trial. Cancer Immunology, Immunotherapy 2001, 50: 269-274. PMID: 11499810, PMCID: PMC11036846, DOI: 10.1007/s002620100199.Peer-Reviewed Original ResearchConceptsIL-2 infusionAdoptive immunotherapyClinical trialsInterleukin-2Low-dose interleukin-2Tumor-sensitized T cellsPhase I clinical trialLymph node cellsPilot clinical trialLymph node lymphocytesTarget cell numberCell numberNode lymphocytesNode cellsTumor regressionT cellsT lymphocytesUnexpected toxicitiesMurine modelAdditional trialsInfusionPhase ITrialsTechnical modificationsPatient cells
2000
Pharmacokinetic and pharmacodynamic evaluation of the glycinamide ribonucleotide formyltransferase inhibitor AG2034.
McLeod HL, Cassidy J, Powrie RH, Priest DG, Zorbas MA, Synold TW, Shibata S, Spicer D, Bissett D, Pithavala YK, Collier MA, Paradiso LJ, Roberts JD. Pharmacokinetic and pharmacodynamic evaluation of the glycinamide ribonucleotide formyltransferase inhibitor AG2034. Clinical Cancer Research 2000, 6: 2677-84. PMID: 10914709.Peer-Reviewed Original ResearchConceptsGlycinamide ribonucleotide formyltransferaseCourse 1Systemic clearanceGrade III/IV toxicityGrade II toxicityMin/m2Rapid systemic clearanceVolume of distributionEvaluable patientsSystemic exposurePharmacodynamic evaluationClinical centersBolus injectionPharmacokinetic approachBlood samplesPatient toxicityPatientsElimination patternReproducible ELISAAG2034Course 3Phase IAnticancer agentsPurine synthesis pathwayDe novo purine synthesis pathwayPhase I study of AG2034, a targeted GARFT inhibitor, administered once every 3 weeks
Roberts J, Shibata S, Spicer D, McLeod H, Tombes M, Kyle B, Carroll M, Sheedy B, Collier M, Pithavala Y, Paradiso L, Clendeninn N. Phase I study of AG2034, a targeted GARFT inhibitor, administered once every 3 weeks. Cancer Chemotherapy And Pharmacology 2000, 45: 423-427. PMID: 10803927, DOI: 10.1007/s002800051012.Peer-Reviewed Original ResearchConceptsDose-limiting toxicityPhase II doseCumulative toxicityAdvanced malignanciesIntravenous bolusAUC0-24Pharmacodynamic factorsFolate supplementationPlasma concentrationsIntermediate dosePharmacokinetic analysisDose levelsELISA assaysDosePhase IAG2034Progressive increaseGARFT inhibitorToxicityWeeksInhibitorsMucositisThrombocytopeniaDiarrheaHyperbilirubinemiaWeekly lometrexol with daily oral folic acid is appropriate for phase II evaluation
Roberts J, Poplin E, Tombes M, Kyle B, Spicer D, Grant S, Synold T, Moran R. Weekly lometrexol with daily oral folic acid is appropriate for phase II evaluation. Cancer Chemotherapy And Pharmacology 2000, 45: 103-110. PMID: 10663624, DOI: 10.1007/s002800050017.Peer-Reviewed Original ResearchConceptsDaily oral folic acidOral folic acidDose omissionsFolic acidDose combinationWeekly scheduleEarlier Phase I trialPredose plasma samplesPhase II dosePhase II trialDose-limiting toxicityPhase I trialPhase II evaluationRed blood cell contentSevere toxic eventsRenal cell carcinomaDays of treatmentAppropriate dose combinationBlood cell contentInfusion weeklyStable diseaseII trialDose intensityPartial responseWeekly administration
1999
Leucovorin, 5-fluorouracil, and gemcitabine: A phase I study
Poplin E, Roberts J, Tombs M, Grant S, Rubin E. Leucovorin, 5-fluorouracil, and gemcitabine: A phase I study. Investigational New Drugs 1999, 17: 57-61. PMID: 10555123, DOI: 10.1023/a:1006239200772.Peer-Reviewed Original ResearchConceptsCombination of leucovorinECOG performance status 0Refractory solid tumor malignanciesMedian performance statusPerformance status 0Phase I trialSolid tumor malignanciesTreatment of lungPrior chemotherapyPrior therapyStatus 0Performance statusStarting doseHepatic reserveI trialPartial responseMedian ageGemcitabine administrationDisease progressionDrug sequenceBreast cancerChemotherapy agentsMedian numberLeucovorinDay 28
1998
Phase Ib trial of bryostatin 1 in patients with refractory malignancies.
Grant S, Roberts J, Poplin E, Tombes MB, Kyle B, Welch D, Carr M, Bear HD. Phase Ib trial of bryostatin 1 in patients with refractory malignancies. Clinical Cancer Research 1998, 4: 611-8. PMID: 9533528.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAntineoplastic AgentsBryostatinsCohort StudiesCytotoxicity, ImmunologicDrug Administration ScheduleFemaleHumansImmunophenotypingInfusions, IntravenousInterleukin-2LactonesLymphocyte ActivationLymphocytesLymphomaMacrolidesMaleMetabolic Clearance RateMiddle AgedNeoplasmsPatient SelectionPlatelet AggregationProtein Kinase CConceptsPhase Ib trialIb trialCohort 3Lymphokine-activated killer cell activityBryostatin 1Bryostatin-1 administrationObjective clinical responsesKiller cell activityLiver function testsSubset of patientsBryostatin 1 treatmentSignificant posttreatment increasePKC activitySplit courseClinical responseFirst doseLiver metastasesNonhematological malignanciesRefractory malignanciesFunction testsPatient cohortCohort 1Interleukin-2Immunophenotypic profileTransient elevation
1991
A phase i clinical trial of didemnin B
Stewart J, Low J, Roberts J, Blow A. A phase i clinical trial of didemnin B. Cancer 1991, 68: 2550-2554. PMID: 1933801, DOI: 10.1002/1097-0142(19911215)68:12<2550::aid-cncr2820681203>3.0.co;2-q.Peer-Reviewed Original ResearchConceptsM2/dDrug-induced liver dysfunctionPhase I clinical trialPhase II doseHepatic enzyme levelsDose-limiting toxicityComplete tumor responseCastor oil vehicleMurine B16 melanomaDidemnin BBolus scheduleClinical bleedingLiver dysfunctionAdvanced cancerAnaphylactic symptomsTumor responseClinical trialsDrug infusionL1210 growthOil vehicleM5076 sarcomaB16 melanomaDose levelsSporadic elevationsToxicologic testsEffect of obesity on plasma insulin-like growth factor-I in cancer patients.
Colletti RB, Copeland KC, Devlin JT, Roberts JD, McAuliffe TL. Effect of obesity on plasma insulin-like growth factor-I in cancer patients. International Journal Of Obesity 1991, 15: 523-7. PMID: 1938095.Peer-Reviewed Original ResearchConceptsMidarm muscle areaTriceps skinfold thicknessIndices of adiposityCancer patientsPlasma IGFNutritional statusPlasma insulin-like growth factor IScreening testPlasma insulin-like growth factorPlasma IGF-I concentrationsInsulin-like growth factor IInsulin-like growth factorUtility of IGFPercent of patientsEffect of obesityBody mass indexIGF-I concentrationsUseful screening testGrowth factor IGender-specific fashionLog IGFMass indexAnthropometric measurementsSkinfold thicknessBody weight
1988
Phase I clinical and pharmacokinetic study of trimetrexate using a daily x5 schedule.
Stewart JA, McCormack JJ, Tong W, Low JB, Roberts JD, Blow A, Whitfield LR, Haugh LD, Grove WR, Lopez AJ. Phase I clinical and pharmacokinetic study of trimetrexate using a daily x5 schedule. Cancer Research 1988, 48: 5029-35. PMID: 2970294.Peer-Reviewed Original ResearchConceptsWhite blood cellsM2/dGood performance status patientsMedian white blood cellPhase IDaily x5 schedulePhase II trialPharmacokinetic studyColon 26 tumorMurine i.Nonhematological toxicitiesPlatelet nadirsPrior therapyII trialStarting doseStatus patientsDose escalationTerminal eliminationDose administeredPlatelet toxicityDaily dosesSchedule dependencyPharmacokinetic analysisB16 melanomaDose levels