2025
Chapter 49 Phase 0 & window of opportunity clinical trials
Reddy A, Bansal U, Lerner S. Chapter 49 Phase 0 & window of opportunity clinical trials. 2025, 249-253. DOI: 10.1016/b978-0-323-90186-4.00009-2.Peer-Reviewed Original ResearchExploratory investigational new drugClinical trialsPhase 1 clinical trialPreclinical animal studiesFood and Drug AdministrationInvestigational new drugOn-target effectsPhase 0 studiesDrug pharmacokineticsDrug efficacyDrug AdministrationAnimal studiesOncology drugsDrug trialsSuboptimal pharmacological propertiesNew drugsDrug approvalDrugDrug approval processCosts associated with drug developmentPharmacological propertiesDrug safetyTrialsDrug developmentTherapeutic areas
2024
Correlation of Body Mass Index with Overall Survival Among Patients with Metastatic Hormone-sensitive Prostate Cancer: Analysis of Patient-level Data from SWOG-1216
Swami U, Jo Y, Narang A, Plets M, Hage Chehade C, Gebrael G, Gupta S, Myint Z, Tangen C, Lara P, Thompson I, Hussain M, Dorff T, Lerner S, Agarwal N. Correlation of Body Mass Index with Overall Survival Among Patients with Metastatic Hormone-sensitive Prostate Cancer: Analysis of Patient-level Data from SWOG-1216. European Urology Oncology 2024 PMID: 39521639, DOI: 10.1016/j.euo.2024.10.013.Peer-Reviewed Original ResearchMetastatic hormone-sensitive prostate cancerHormone-sensitive prostate cancerAndrogen deprivation therapyBody mass indexAssociated with better OSHigher body mass indexOverall survivalPhase 3 trialProstate cancerMass indexMetastatic castration-resistant prostate cancerAssociated with better overall survivalBaseline prostate-specific antigenCastration-resistant prostate cancerNormal body mass indexIncidence of visceral metastasesBaseline body mass indexZubrod performance statusCorrelation of body mass indexAnalysis of patient-level dataProstate-specific antigenGroup of patientsPost hoc exploratory analysisRisk of deathMedian OSDNA Damage Response Alterations Predict for Neoadjuvant Chemotherapy Sensitivity in Muscle-Invasive Bladder Cancer: A Correlative Analysis of the SWOG S1314 Trial
Iyer G, Tangen C, Sarfaty M, Regazzi A, Lee I, Fong M, Choi W, Dinney C, Flaig T, Thompson I, Lerner S, McConkey D, Rosenberg J. DNA Damage Response Alterations Predict for Neoadjuvant Chemotherapy Sensitivity in Muscle-Invasive Bladder Cancer: A Correlative Analysis of the SWOG S1314 Trial. JCO Precision Oncology 2024, 8: e2400287. PMID: 39499893, DOI: 10.1200/po.24.00287.Peer-Reviewed Original ResearchConceptsNeoadjuvant cisplatin-based chemotherapyMuscle-invasive bladder cancerProgression-free survivalDDR alterationsDNA damage response alterationPathological responseBladder cancerDNA damage responseAssociated with pathological responseNeoadjuvant chemotherapy sensitivityPretreatment tumor specimensPathological response rateCisplatin-based chemotherapyDNA damage response genesEstimates of hazard ratiosOverall survivalRadical cystectomyTumor specimensPerformance statusClinical stageChemotherapy sensitivityCox regressionHazard ratioNext-generation sequencingPatientsEligibility and Endpoints for Clinical Trials in Trimodality Therapy for Bladder Cancer
Singh P, Ballas L, Sonpavde G, Chen R, Bangs R, Bauman B, Nagar H, Delacroix S, Lerner S, Efstathiou J. Eligibility and Endpoints for Clinical Trials in Trimodality Therapy for Bladder Cancer. Bladder Cancer 2024, 10: 199-213. PMID: 39493817, PMCID: PMC11530036, DOI: 10.3233/blc-240036.Peer-Reviewed Original ResearchBladder cancer treatmentTransurethral resection of bladder tumorEastern Cooperative Oncology GroupTrimodality therapyLong-term outcomesClinical trialsCancer treatmentRadical cystectomySystemic therapyEligibility criteriaSecondary endpointsTrial eligibility criteriaBladder cancerMaximal transurethral resection of bladder tumorEndpoint definitionsAlternative to radical cystectomyResection of bladder tumorCo-primary end pointsConcurrent systemic therapyMaximal transurethral resectionPhase II/III clinical trialsLocalized bladder cancerEvent-free survivalCooperative Oncology GroupBladder cancer researchStandard or Extended Lymphadenectomy for Muscle-Invasive Bladder Cancer
Lerner S, Tangen C, Svatek R, Daneshmand S, Pohar K, Skinner E, Schuckman A, Sagalowsky A, Smith N, Kamat A, Kassouf W, Plets M, Bangs R, Koppie T, Alva A, La Rosa F, Pal S, Kibel A, Canter D, Thompson I. Standard or Extended Lymphadenectomy for Muscle-Invasive Bladder Cancer. New England Journal Of Medicine 2024, 391: 1206-1216. DOI: 10.1056/nejmoa2401497.Peer-Reviewed Original ResearchCirculating Tumor Cell Count and Overall Survival in Patients With Metastatic Hormone-Sensitive Prostate Cancer
Goldkorn A, Tangen C, Plets M, Bsteh D, Xu T, Pinski J, Ingles S, Triche T, MacVicar G, Vaena D, Crispino A, McConkey D, Lara P, Hussain M, Quinn D, Dorff T, Lerner S, Thompson I, Agarwal N. Circulating Tumor Cell Count and Overall Survival in Patients With Metastatic Hormone-Sensitive Prostate Cancer. JAMA Network Open 2024, 7: e2437871. PMID: 39374015, PMCID: PMC11581504, DOI: 10.1001/jamanetworkopen.2024.37871.Peer-Reviewed Original ResearchConceptsMetastatic hormone-sensitive prostate cancerMetastatic castration-resistant prostate cancerCirculating tumor cell countCirculating tumor cellsHormone-sensitive prostate cancerTumor cell countOverall survivalProstate cancerPrognostic valueCTC countsPrognostic factorsProgression to metastatic castration-resistant prostate cancerDiagnosed mHSPCPeripheral blood circulating tumor cellsClinical trialsBlood circulating tumor cellsCastration-resistant prostate cancerPrognostic studyCell countBaseline CTC countProgression-free survivalLines of therapyEnhanced overall survivalProstate-specific antigenIncreased prognostic valueFinal Overall Survival Analysis of S1500: A Randomized, Phase II Study Comparing Sunitinib With Cabozantinib, Crizotinib, and Savolitinib in Advanced Papillary Renal Cell Carcinoma
Barata P, Tangen C, Plets M, Thompson I, Narayan V, George D, Heng D, Shuch B, Stein M, Gulati S, Tretiakova M, Tripathi A, Bjarnason G, Humphrey P, Adeniran A, Vaishampayan U, Alva A, Zhang T, Cole S, Lara P, Lerner S, Balzer-Haas N, Pal S. Final Overall Survival Analysis of S1500: A Randomized, Phase II Study Comparing Sunitinib With Cabozantinib, Crizotinib, and Savolitinib in Advanced Papillary Renal Cell Carcinoma. Journal Of Clinical Oncology 2024, 42: 3911-3916. PMID: 39255440, PMCID: PMC11575905, DOI: 10.1200/jco.24.00767.Peer-Reviewed Original ResearchAdvanced papillary renal cell carcinomaPapillary renal cell carcinomaRenal cell carcinomaOverall survivalCell carcinomaProlonged progression-free survivalLack of survival benefitProgression-free survivalRandomized phase IIMedian follow-upPrimary end pointOpen-label trialOverall survival analysisCrizotinib armMedian OSSurvival benefitClinical trial updateNo significant differenceCabozantinibTreatment armsSunitinibFollow-upClinical trialsSavolitinibCrizotinibMitochondrial reprogramming by activating OXPHOS via glutamine metabolism in African American patients with bladder cancer
Reddy K, Piyarathna D, Park J, Putluri V, Amara C, Kamal A, Xu J, Kraushaar D, Huang S, Jung S, Eberlin L, Johnson J, Kittles R, Ballester L, Parsawar K, Siddiqui M, Gao J, Gramer A, Bollag R, Terris M, Lotan Y, Creighton C, Lerner S, Sreekumar A, Kaipparettu B, Putluri N. Mitochondrial reprogramming by activating OXPHOS via glutamine metabolism in African American patients with bladder cancer. JCI Insight 2024, 9: e172336. PMID: 39253977, PMCID: PMC11385078, DOI: 10.1172/jci.insight.172336.Peer-Reviewed Original ResearchConceptsBladder cancerOxidative phosphorylationComponents of complex IComplex IElevated mitochondrial oxidative phosphorylationComprehensive RNA-seqReduced basal respirationActive oxidative phosphorylationMitochondrial oxidative phosphorylationDecreased tumor growthTumor growth potentialIncreased disease progressionMitochondrial respiration rateAfrican American patientsRNA-seqRace-specific differencesMitochondrial reprogrammingEuropean AmericansMetabolic rewiringOXPHOS activityBasal respirationGlutamine metabolismGLS1 expressionPreclinical studiesATP production1620P Inherited variants in SRD5A genes and response to hormonal therapy in prostate cancer (SWOG S1216)
Ingles S, Pinski J, Manojlovic Z, Xiong S, Weisenberger D, Goldkorn A, Tangen C, McConkey D, Lara P, Hussain M, Quinn D, Thompson I, Lerner S, Dorff T, Agarwal N. 1620P Inherited variants in SRD5A genes and response to hormonal therapy in prostate cancer (SWOG S1216). Annals Of Oncology 2024, 35: s978. DOI: 10.1016/j.annonc.2024.08.1701.Peer-Reviewed Original ResearchLong‐term outcomes of bladder‐sparing therapy vs radical cystectomy in BCG‐unresponsive non‐muscle‐invasive bladder cancer
Taylor J, Kamat A, O'Donnell M, Annapureddy D, Howard J, Tan W, McElree I, Davaro F, Yim K, Harrington S, Dyer E, Black A, Kanabur P, Roumiguié M, Lerner S, Black P, Raman J, Preston M, Steinberg G, Huang W, Li R, Packiam V, Woldu S, Lotan Y. Long‐term outcomes of bladder‐sparing therapy vs radical cystectomy in BCG‐unresponsive non‐muscle‐invasive bladder cancer. BJU International 2024 PMID: 39183466, DOI: 10.1111/bju.16509.Peer-Reviewed Original ResearchNon-muscle-invasive bladder cancerBladder-sparing therapyUpfront RCRadical cystectomyCohort of patientsBladder cancerBCG-unresponsive NMIBCRetrospective cohort of patientsProgression to MIBCUpfront radical cystectomyCancer-specific survivalInstitutional review board approvalMetastasis-free survivalFood and Drug Administration criteriaRate of recurrenceReview board approvalLong-term outcomesStatistically significant differenceNodal diseaseRe-resectionSystemic immunotherapyIntravesical chemotherapyOncological outcomesOverall survivalOncological riskBladder-sparing Therapy for Bacillus Calmette-Guérin–unresponsive Non–muscle-invasive Bladder Cancer: International Bladder Cancer Group Recommendations for Optimal Sequencing and Patient Selection
Li R, Hensley P, Gupta S, Al-Ahmadie H, Babjuk M, Black P, Brausi M, Bree K, Fernández M, Guo C, Horowitz A, Lamm D, Lerner S, Lotan Y, Mariappan P, McConkey D, Mertens L, Mir C, Ross J, O'Donnell M, Palou J, Pohar K, Steinberg G, Soloway M, Spiess P, Svatek R, Tan W, Taoka R, Buckley R, Kamat A. Bladder-sparing Therapy for Bacillus Calmette-Guérin–unresponsive Non–muscle-invasive Bladder Cancer: International Bladder Cancer Group Recommendations for Optimal Sequencing and Patient Selection. European Urology 2024 PMID: 39183090, DOI: 10.1016/j.eururo.2024.08.001.Peer-Reviewed Original ResearchNon-muscle-invasive bladder cancerInternational Bladder Cancer GroupBladder-sparing treatmentCarcinoma in situNadofaragene firadenovecRadical cystectomyBladder cancerOptimal selection of patientsAbsence of randomized trialsBladder-sparing therapySingle-agent chemotherapyBladder cancer groupSelection of patientsDevelopment of agentsPatient selectionSystemic toxicityCancer groupUnapproved agentsClinical trial participationPatient characteristicsRandomized trialsMitomycin CTumor attributesConsensus recommendationsCancer expertsAdjuvant Everolimus in Non–Clear Cell Renal Cell Carcinoma
Gulati S, Tangen C, Ryan C, Vaishampayan U, Shuch B, Barata P, Pruthi D, Bergerot C, Tripathi A, Lerner S, Thompson I, Lara P, Pal S. Adjuvant Everolimus in Non–Clear Cell Renal Cell Carcinoma. JAMA Network Open 2024, 7: e2425288. PMID: 39106067, PMCID: PMC11304111, DOI: 10.1001/jamanetworkopen.2024.25288.Peer-Reviewed Original ResearchConceptsChromophobe renal cell carcinomaRecurrence-free survivalPapillary renal cell carcinomaRenal cell carcinomaNon-clear cell renal cell carcinomaResected renal cell carcinomaCell renal cell carcinomaOverall survivalWeeks of treatmentCell carcinomaAdverse eventsClinical trialsHazard ratioPhase 3 randomized clinical trialWeeks of everolimusHigher adverse eventsRate of adverse eventsIntermediate-high riskIntervention groupVery-high-riskCox regression modelsPotential treatment benefitsClinical trial dataTreatment-naivePartial nephrectomyPathological concordance rate and outcomes by subtype in advanced papillary renal cell carcinoma
Tripathi A, Tangen C, Plets M, Li X, Tretiakova M, Humphrey P, Adeniran A, Barata P, Gulati S, Bergerot C, Pruthi D, Thompson I, Lara P, Lerner S, Pal S, Shuch B. Pathological concordance rate and outcomes by subtype in advanced papillary renal cell carcinoma. BJU International 2024, 134: 596-601. PMID: 39014969, DOI: 10.1111/bju.16403.Peer-Reviewed Original ResearchPapillary renal cell carcinomaPositive predictive valueRenal cell carcinomaLocal pathology reviewCentral reviewPathology reviewCell carcinomaAdvanced papillary renal cell carcinomaMetastatic papillary renal cell carcinomaPapillary renal cell carcinoma subtypesPatients treated with targeted therapyExpert genitourinary pathologistsPathological concordance rateLocal reviewGenitourinary pathologistsClinical benefitCabozantinibClinical significanceClinical valueSubtype assignmentConcordance rateType 1CarcinomaPatientsPredictive valueCorrelative Analysis of ATM, RB1, ERCC2, and FANCC Mutations and Pathologic Complete Response After Neoadjuvant Chemotherapy in Patients with Muscle-invasive Bladder Cancer: Results from the SWOG S1314 Trial
Plimack E, Tangen C, Plets M, Kokate R, Xiu J, Nabhan C, Ross E, Grundy E, Choi W, Dinney C, Lee I, Fong M, Lucia M, Daneshmand S, Theodorescu D, Goldkorn A, Lerner S, Flaig T, McConkey D. Correlative Analysis of ATM, RB1, ERCC2, and FANCC Mutations and Pathologic Complete Response After Neoadjuvant Chemotherapy in Patients with Muscle-invasive Bladder Cancer: Results from the SWOG S1314 Trial. European Urology 2024, 86: 297-300. PMID: 39003201, PMCID: PMC11416320, DOI: 10.1016/j.eururo.2024.06.018.Peer-Reviewed Original ResearchMuscle-invasive bladder cancerCisplatin-based chemotherapyNeoadjuvant chemotherapyBladder cancerTumor samplesNeoadjuvant cisplatin-based chemotherapyResponse to NACClinical assessmentDose-dense methotrexateTiming of cystectomyPathological complete responseClinical trials of chemotherapyTrials of chemotherapyNational clinical trialNeoadjuvant gemcitabineBladder preservationComplete responseTumor specimensSurgical specimensMulticenter trialPatient selectionTreatment armsGene panelChemotherapyGene mutationsBone Pain and Survival Among Patients With Metastatic, Hormone-Sensitive Prostate Cancer
Gebrael G, Jo Y, Swami U, Plets M, Chehade C, Narang A, Gupta S, Myint Z, Sayegh N, Tangen C, Hussain M, Dorff T, Lara P, Lerner S, Thompson I, Agarwal N. Bone Pain and Survival Among Patients With Metastatic, Hormone-Sensitive Prostate Cancer. JAMA Network Open 2024, 7: e2419966. PMID: 38980676, PMCID: PMC11234233, DOI: 10.1001/jamanetworkopen.2024.19966.Peer-Reviewed Original ResearchConceptsProgression-free survivalAndrogen deprivation therapyProstate-specific antigenHormone-sensitive prostate cancerBone painOverall survivalPost hoc secondary analysisProstate cancerSurvival outcomesPain statusAssociated with shorter progression-free survivalClinical trialsPresence of bone painProstate-specific antigen levelAssociated with worse overall survivalCastration-resistant prostate cancerShorter progression-free survivalIntention-to-treat populationSecondary analysisZubrod performance statusHigh-volume diseaseCompare survival outcomesCox proportional hazards regression modelsSecondary end pointsProportional hazards regression modelsAdjuvant Everolimus in Patients with Completely Resected, Very High-risk Renal Cell Carcinoma of Clear Cell Histology: Results from the Phase 3 Placebo-controlled SWOG S0931 (EVEREST) Trial
Lara P, Tangen C, Heath E, Gulati S, Stein M, Meng M, Alva A, Pal S, Puzanov I, Clark J, Choueiri T, Agarwal N, Uzzo R, Haas N, Synold T, Plets M, Vaishampayan U, Shuch B, Lerner S, Thompson I, Ryan C. Adjuvant Everolimus in Patients with Completely Resected, Very High-risk Renal Cell Carcinoma of Clear Cell Histology: Results from the Phase 3 Placebo-controlled SWOG S0931 (EVEREST) Trial. European Urology 2024, 86: 258-264. PMID: 38811313, DOI: 10.1016/j.eururo.2024.05.012.Peer-Reviewed Original ResearchRecurrence-free survivalHigh-risk diseaseRenal cell cancerPhase 3 trialOverall survivalEverolimus armCell histologyPlacebo armDiscontinuation rate due to adverse eventsHigh-risk renal cell carcinomaCompare recurrence-free survivalPatients treated with everolimusPositive phase 3 trialClear cell renal cell cancerCell renal cell cancerRate of side effectsClear cell histologyComparison to placeboComplete surgical removalNode-positive statusRisk of recurrenceRisk stratification toolCox regression modelsAdjuvant sunitinibAdjuvant trialsA phase III randomized trial of eribulin (E) with gemcitabine (G) vs standard of care (SOC) for patients (pts) with metastatic urothelial carcinoma (mUC) refractory to or ineligible for PD/PDL1 antibody (Ab): SWOG S1937 updated design.
Sadeghi S, Plets M, Lara P, Tangen C, Berg S, Brown J, Bangs R, Nakagawa D, Daneshmand S, Ian M. Jr., Flaig T, Petrylak D, Lerner S. A phase III randomized trial of eribulin (E) with gemcitabine (G) vs standard of care (SOC) for patients (pts) with metastatic urothelial carcinoma (mUC) refractory to or ineligible for PD/PDL1 antibody (Ab): SWOG S1937 updated design. Journal Of Clinical Oncology 2024, 42: tps4617-tps4617. DOI: 10.1200/jco.2024.42.16_suppl.tps4617.Peer-Reviewed Original ResearchProgression free survivalMetastatic urothelial carcinomaMedian progression free survivalStandard of careOverall survivalEnfortumab vedotinSacituzumab govitecanFree survivalCisplatin-ineligible metastatic urothelial carcinomaPhase III randomized trialMedian overall survivalStudies of eribulinEndpoint of OSFGFR alterationsLiver metastasesSystemic therapyEligible ptsUrothelial carcinomaPrimary endpointGenitourinary cancersTreatment changesEribulinResponse rateActivity of EORRCorrelation of body mass index (BMI) with survival outcomes in patients (pts) with metastatic hormone-sensitive prostate cancer (mHSPC): Analysis of patient (pt)-level data from SWOG 1216 study.
Swami U, Jo Y, Narang A, Plets M, Hage Chehade C, Gebrael G, Gupta S, Myint Z, Tangen C, Lara P, Thompson I, Hussain M, Dorff T, Lerner S, Agarwal N. Correlation of body mass index (BMI) with survival outcomes in patients (pts) with metastatic hormone-sensitive prostate cancer (mHSPC): Analysis of patient (pt)-level data from SWOG 1216 study. Journal Of Clinical Oncology 2024, 42: 5081-5081. DOI: 10.1200/jco.2024.42.16_suppl.5081.Peer-Reviewed Original ResearchMetastatic hormone-sensitive prostate cancerBody mass indexBody mass index cohortZubrod performance statusCorrelation of body mass indexPhase III studyOverall survivalSurvival outcomesGleason scoreIII studiesPerformance statusProstate cancerMetastatic hormone-sensitive prostate cancer settingAssociated with improved survival outcomesMetastatic castration-resistant prostate cancerMultivariate analysisHormone-sensitive prostate cancerAssociated with better OSRandomized phase III studyCastration-resistant prostate cancerNormal body mass indexCategorized body mass indexPrognostication of patientsAssociation of obesityDisease burdenEfficacy of Intravesical Nadofaragene Firadenovec for Patients With Bacillus Calmette-Guérin–Unresponsive Nonmuscle-Invasive Bladder Cancer: 5-Year Follow-Up From a Phase 3 Trial
Narayan V, Boorjian S, Alemozaffar M, Konety B, Shore N, Gomella L, Kamat A, Bivalacqua T, Montgomery J, Lerner S, Busby J, Poch M, Crispen P, Steinberg G, Schuckman A, Downs T, Mashni J, Lane B, Guzzo T, Bratslavsky G, Karsh L, Woods M, Brown G, Canter D, Luchey A, Lotan Y, Inman B, Williams M, Cookson M, Chang S, Sankin A, O’Donnell M, Sawutz D, Philipson R, Parker N, Yla-Herttuala S, Rehm D, Jakobsen J, Juul K, Dinney C. Efficacy of Intravesical Nadofaragene Firadenovec for Patients With Bacillus Calmette-Guérin–Unresponsive Nonmuscle-Invasive Bladder Cancer: 5-Year Follow-Up From a Phase 3 Trial. Journal Of Urology 2024, 212: 74-86. PMID: 38704840, DOI: 10.1097/ju.0000000000004020.Peer-Reviewed Original ResearchConceptsNonmuscle-invasive bladder cancerPhase 3 trialBladder cancerFollow-upAdenoviral vector-based gene therapyProgression to muscle-invasive diseaseOpen-label phase 3 trialVector-based gene therapyCystectomy-free survivalMuscle-invasive diseaseMedian follow-upCarcinoma in situBladder preservationNadofaragene firadenovecOverall survivalGene therapyCytological assessmentTa/T1PatientsUS sitesCohortReceiving treatmentMonthsCancerHGRFP2-03 SWOG S1011–SUBGROUP ANALYSIS OF THE PHASE III SURGICAL TRIAL TO EVALUATE THE BENEFIT OF A STANDARD VERSUS AN EXTENDED LYMPHADENECTOMY PERFORMED AT TIME OF RADICAL CYSTECTOMY FOR MUSCLE INVASIVE UROTHELIAL CANCER
Lerner S, Tangen C, Svatek R, Daneshmand S, Pohar K, Skinner E, Schuckman A, Sagalowsky A, Smith N, Kamat A, Kassouf W, Plets M, Bangs R, Koppie T, Alva A, La Rosa F, Pal S, Kibel A, Canter D, Thompson I. P2-03 SWOG S1011–SUBGROUP ANALYSIS OF THE PHASE III SURGICAL TRIAL TO EVALUATE THE BENEFIT OF A STANDARD VERSUS AN EXTENDED LYMPHADENECTOMY PERFORMED AT TIME OF RADICAL CYSTECTOMY FOR MUSCLE INVASIVE UROTHELIAL CANCER. Journal Of Urology 2024, 211 DOI: 10.1097/01.ju.0001015816.87470.c9.03.Peer-Reviewed Original Research