Center for Early Phase Trials
- To change the way cancer research is done so that treatments that positively impact the lives of patients can be discovered and advanced.
- We have established that a well-performing early-phase design can have a tremendous impact on oncology drug development, increasing the chances that an effective therapy will be identified and put forward for therapeutic use
- Empower and educate clinical investigators through team science, including refining study objectives and tailoring designs to meet those objectives.
- Create dose-finding designs for targeted agents and immunotherapies, multi-drug combinations, patient heterogeneity, delayed toxicities, and personalized dosing.
- We develop free user-friendly web applications for designing and conducting early-phase clinical trials, which facilitates efficient team science.
- Mark R. Conaway, Ph.D. (Director)
- Gina R. Petroni, Ph.D. (Co-Director)
- Bethany J. Horton, Ph.D.
- Nikole Varhegyi, M.S.
- Nolan A. Wages, Ph.D. (Department of Biostatistics, VCU, Richmond – since May 2022)
- Ben Brewer, M.S.
- NIH/NCI R01CA142859 (PI: Conaway). Designs for phase I trials of combinations of agents. 2010-2013.
- NIH/NCI R01CA142859 (PI: Conaway). Designs for phase I trials in heterogeneous groups. 2014-2019.
- NIH/NCI K25CA181638 (PI: Wages). Phase I designs for combined immunotherapies in cancer. 2014-2019.
- NIH/NCI R03CA238966 (PI: Wages). Dose-finding designs for adoptive cell therapy trials. 2019-2021.
- NIH/NCI R01CA247932 (PI: Wages). Dose finding designs for late-onset toxicities. 2021-2024.
- Wages NA, Horton BJ, Conaway MR, Petroni GR; Operating characteristics are needed to properly evaluate the scientific validity of phase I protocols; 2021; Contemp Clin Trials 108: 106517
- Wages NA, Iasonos A, O’Quigley J, Conaway MR; Coherence principles in interval-based dose-finding; 2020; Pharm Stat 19: 137-144
- Conaway MR, Petroni GR; The impact of early phase trial design in the drug development process; 2019; Clin Cancer Res 25: 819-827
- Hobbs BP, Barata PC, Kanjanapan Y, Paller CJ, Perlmutter J, Pond GR, Prowell TM, Rubin EH, Seymour LK, Wages NA, Yap TA, Feltquate D, Garrett-Mayer E, Grossman W, Hong DS, Ivy SP, Siu LL, Reeves SA, Rosner GL; Seamless designs: current practice and considerations for early phase drug development in oncology; 2019; J Natl Cancer Inst 11: 118-128
- Wages NA, Bagley E; Evaluation of irrational dose assignment definitions using the continual reassessment method; 2019; Clin Trials 16: 665-672
- Wages NA, Yuan Y; Preface to the themed issue on ‘Early phase clinical trial design methodology.’; 2019; J R Stat Soc Ser C Appl Stat 68: 267-269
- Wages NA, Braun TM; Accuracy, safety, and reliability of novel phase I designs – letter; 2018; Clin Cancer Res 24: 5482
- Wages NA, Conaway MR; Revisiting isotonic phase I design in the era of model-assisted dose-finding; 2018; Clin Trials 15: 524-529
- Wages NA, Petroni GR; A web tool for designing and conducting phase I trials using the continual reassessment method; 2018; BMC Cancer 18:133
- Horton BJ, Wages NA, Conaway MR; Performance of toxicity probability interval based designs in contrast to the continual reassessment method; 2017; Stat Med 36: 291-300
- Petroni GR, Wages NA, Paux G, Dubois F; Implementation of adaptive methods in early-phase clinical trials; 2017; Stat Med 36: 215-224
- Wages NA, Varhegyi N; A web application for evaluating phase I methods using a non-parametric optimal benchmark; 2017; Clin Trials 14: 553-557
- Iasonos A, Wages NA, Conaway MR, Cheung K, Yuan Y, O’Quigley J; Dimension of model parameter space and operating characteristics in adaptive dose-finding studies; 2016; Stat Med 35: 3760-3775
- Wages NA, Conaway MR, O’Quigley J; Performance of two-stage continual reassessment method relative to an optimal benchmark; 2013; Clin Trials 10: 862-75
- O’Quigley J, Conaway MR; Extended model-based designs for more complex dose-finding studies; 2011; Stat Med 30: 2062-2069
- O’Quigley J, Conaway MR; Continual reassessment and related dose-finding designs; 2010; Stat Sci 25: 202-216
- Conaway MR, Dunbar S, Peddada SD; Designs for single‐or multiple‐agent phase I trials; 2004; Biometrics 60: 661-669
- Conaway MR, Petroni GR; Designs for phase II trials allowing for a trade-off between response and toxicity; 1996; Biometrics 52: 1375-1386
- Conaway MR, Petroni GR; Bivariate sequential designs for phase II trials; 1995; Biometrics 51: 656-664
- Wages NA, Millard TA, Dillon PM, Brenin CM, Petroni GR; Efficient dose-finding for drug combination studies involving a shift in study populations; 2020; Contemp Clin Trials Commun 17: 100519
- Horton BJ, O’Quigley J, Conaway MR; Consequences of performing parallel dose finding trials in heterogeneous groups of patients; 2019; JNCI Cancer Spectr 3: pkz013
- Horton BJ, Wages NA, Conaway MR; Shift models for dose finding in partially ordered groups; 2019; Clin Trials 16: 32-40
- Conaway MR; Isotonic designs for phase I trials in partially ordered groups; 2017; Clin Trials 14: 491-498
- Conaway MR; A design for phase I trials in completely or partially ordered groups; 2017; Stat Med 36: 2323-2332
- Conaway MR, Wages NA; Designs for phase I trials in ordered groups; 2017; Stat Med 36: 254-265
- Wages NA, Read PW, Petroni GR; A phase I/II adaptive design for heterogeneous groups with application to a stereotactic body radiation trial; 2015; Pharm Stat 14: 302-310
- EM Bagley, NA Wages; Impact of dose feasibility on the conduct of phase I trials of adoptive cell therapy; 2022; Contemp Clin Trials Comm 25: 100877
- Wages NA, Fadul CE; Adaptive dose finding based on safety and feasibility in early-phase clinical trials of adoptive cell immunotherapy; 2020; Clin Trials 17: 157-165
- Wages NA, Slingluff CL; Flexible phase I-II design for partially ordered regimens with application to therapeutic cancer vaccines; 2020; Stat Biosci 12: 104-123
- Wages NA, Slingluff CL, Bullock TN, Petroni GR; Tailoring early-phase clinical trial design to address multiple research objectives; 2020; Cancer Immunol Immunother 69: 95-102
- Yan D, Tait C, Wages NA, Kindwall-Keller T, Dressler EV; Generalization of the time-to-event continual reassessment method to bivariate outcomes; 2019; J Biopharm Stat 29: 635-647
- Yan D, Wages NA, Dressler EV; Improved adaptive randomization strategies for a seamless phase I/II dose-finding design; 2019; J Biopharm Stat 29: 333-347
- Wages NA, Chiuzan C, Panageas KS; Design considerations for early-phase clinical trials of immune-oncology agents; 2018; J Immunother Cancer 6: 81
- Wages NA, Portell CA, Williams ME, Conaway MR, Petroni GR; Implementation of a model-based design in a phase 1b study of combined targeted agents; 2017; Clin Cancer Res 23: 7158-7164
- Wages NA, Slingluff CL, Petroni GR; Statistical controversies in clinical research: early-phase adaptive design for combination immunotherapies; 2017; Ann Oncol 28: 696-701
- Wages NA, Slingluff CL, Petroni GR; A phase I/II adaptive design to determine the optimal treatment regimen from a set of combination immunotherapies in high-risk melanoma; 2015; Contemp Clin Trials 41: 172-179
- Wages NA, Tait C; Seamless phase I/II adaptive design for oncology trials of molecularly targeted agents; 2015; J Biopharm Stat 25: 903-920
- Clertant M, Wages NA, O’Quigley J; Semi-parametric dose finding methods for partially ordered drug combination trials; 2021; Stat Sin [epub ahead of print] March 18
- Wages NA, Reed DR, Keng MK, Conaway MR, Petroni GR; Adapting isotonic dose-finding to a dynamic set of drug combinations with application to a phase I leukemia trial; 2021; Clin Trials [epub ahead of print] Jan 11
- Wages NA; Identifying a maximum tolerated contour in two-dimensional dose-finding; 2017; Stat Med 36: 215-224
- Wages NA, Ivanova A, Marchenko O; Practical designs for phase I combination studies in oncology; 2016; J Biopharm Stat 26: 150-166
- Hirakawa A, Wages NA, Sato H, Matsui S; A comparative study of adaptive dose-finding designs for phase I oncology trials of combination therapies; 2015; Stat Med 34: 3194-3213
- Wages NA, Conaway MR, Slingluff CL, Williams ME, Portell CA, Hwu P, Petroni GR; Recent developments in the implementation of novel designs for early-phase combination studies; 2015; Ann Oncol 26: 1036-1037
- Wages NA, Conaway MR; Phase I/II adaptive design for drug combination oncology trials; 2014; Stat Med 33: 1990-2003
- Wages NA, Conaway MR; Specifications of a continual reassessment method design for phase I trials of combined drugs; 2013; Pharm Stat 12: 217-224
- Wages NA, Conaway MR, O’Quigley J; Using the time-to-event continual reassessment method in the presence of partial orders; 2013; Stat Med 32: 131-141
- Wages NA, Varhegyi N; pocrm: An R package for Phase I trials of combinations of agents; 2013; Comput Methods Programs Biomed 112: 211-218
- Wages NA, Conaway MR, O’Quigley J; Continual reassessment method for partial ordering; 2011; Biometrics 67: 1555-1563
- Wages NA, Conaway MR, O’Quigley J; Dose-finding design for multi-drug combinations; 2011; Clin Trials 8: 380-389
- Wages NA, O’Quigley J, Conaway MR; Phase I design for completely or partially ordered treatment schedules; 2014; Stat Med 33: 569-579
- Conaway MR, Petroni GR “Dose-Finding and Dose-ranging Studies” Principles and Practice of Clinical Trials. 2021; eds. Steven Piantadosi and Curtis L. Meinert (Eds). Springer Nature.
- Conaway MR “Dose-Finding Using the Continual Reassessment Method” Oncology Clinical Trials: Successful Design, Conduct, and Analysis, 2nd edition. 2018; eds. WK Kelly, DO, S Halabi, PhD, Springer Publishing Company
- Wages, NA “Innovative Phase I Clinical Trials” Oncology Clinical Trials: Successful Design, Conduct, and Analysis, 2nd edition. 2018; eds. WK Kelly, DO, S Halabi, PhD, Springer Publishing Company
- Wang H, Petroni GR “Design of Phase II Trials’ Oncology Clinical Trials: Successful Design, Conduct, and Analysis, 2nd edition. 2018; eds. WK Kelly, DO, S Halabi, PhD, Springer Publishing Company
- Conaway MR “Patient Heterogeneity in Dose-Finding Trials” Handbook of Methods for Designing, Monitoring, and Analyzing Dose-Finding Trials. 2017; eds. John O’Quigley, Alexia Iasonos, Björn Bornkamp. CRC Press
- Conaway MR, Wages NA “Phase I Trials and Dose Finding” Cancer Clinical Trials: Current and Controversial Issues in Design and Analysis. 2016; eds. Stephen L. George, Xiaofei Wang, Herbert Pang. CRC Press
- Petroni GR, Conaway, MR “Phase II trials with combined response and toxicity endpoints” Handbook of Statistics in Clinical Oncology, 3nd edition. 2011; ed. Crowley, J. Marcel Dekker
- Wang H, Conaway MR, Petroni, GR “Phase II Trial Design” Oncology Clinical Trials: Successful Design, Conduct, and Analysis, 1st edition. 2010; eds. Halabi, S. and Kelly, W. Springer Publishing Company
- Petroni, GR “Design Issues for Early-Stage Clinical Trials for Cancer Vaccines” Immunotherapy of Cancer. 2006; ed. Nora Disis. Humana Press
- Petroni GR, Conaway, MR “Phase II trials with combined response and toxicity endpoints” Handbook of Statistics in Clinical Oncology, 2nd edition. 2004; ed. Crowley, J. Marcel Dekker
- Petroni GR, Conaway, MR “Phase II trials with combined response and toxicity endpoints” Handbook of Statistics in Clinical Oncology. 2001; ed. Crowley, J. Marcel Dekker
- Slingluff CL, A Multipeptide Vaccine Plus Toll-Like Receptor Agonists in Melanoma Patients (MEL58), NCT01585350, 2012
- Read PW, Phase 1/2 Study to Determine Optimal Dose for Treating Bone Metastases Using Novel STAT-RT Workflow, NCT02145286, 2014
- Slingluff CL, A phase I/II trial of long peptide vaccine plus TLR agonists (Mel 60), NCT02126579, 2014
- Portell C, Optimal dose finding study of ABT-199 and ibrutinib in MCL (ABT-199), NCT02419560, 2015
- Slingluff CL, Safety Study of a Helper Peptide Vaccine Plus Adjuvant Combinations for the Treatment of Melanoma (Mel63), NCT02425306, 2015
- Lau C, Study to Evaluate Adenosine 2A Receptor Agonist (Regadenoson) in Patients Undergoing Lung Transplantation, NCT03072589, 2017
- Dillon P, A Pilot Study of the Combination of Entinostat With Capecitabine in High Risk Breast Cancer After Neo-adjuvant Therapy (Breast49), NCT03473639, 2018
- Douvas M, Phase I study of inotuzumab with augmented BFM re-Induction for younger adults with relapsed/refractory B-cell ALL, NCT03962465, 2019
- Slingluff CL, Melanoma vaccine against neoantigen and shared antigens by CD40 activation and TLR agonists in patients with melanoma (Mel66), NCT04364230, 2020
- Ballen K, Study of Tagraxofusp for Post-Transplant Maintenance for Patients With CD 123+ AML, MF and CMML (HSCT 002), NCT05233618, 2022
- Jones DR, Moskaluk CA, Gillenwater HH, Petroni GR, Burks SG, Philips J, Rehm PK, Olazagasti J, Kozower BD, Bao Y; A phase I trial of induction histone deacetylase and proteasome inhibition followed by surgery in non-small-cell lung cancer; J Thorac Oncol 2012; 7:1683-1690; Design details
- Melssen MM, Petroni GR, Chianese-Bullock KA, Wages NA, Grosh WW, Varhegyi N, Smolkin ME, Smith KT, Galeassi NV, Deacon DH, Gaughan EM, Slingluff CL Jr; A multipeptide vaccine plus toll-like receptor agonists LPS or polyICLC in combination with IFA in melanoma patients (Mel 58); J Immunother Cancer 2019; 7: 163; Design details
- Muller DA, Wages NA, Wilson DD, Dutta SW, Alonso CE, Handsfield LL, Chen Q, Smith AB, Romano KD, Janowski EM, Showalter TN, Larner JM, Read PW; STAT RAD: Prospective Dose Escalation Clinical Trial of Single Fraction Scan-Plan-QA-Treat Stereotactic Body Radiation Therapy for Painful Osseous Metastases; Pract Radiat Oncol. 2020 Nov-Dec; 10(6):e444-e451; Design details
- Lau CL, Beller JP, Boys JA, Zhao Y, Phillips J, Cosner M, Conaway MR, Petroni G, Charles EJ, Mehaffey JH, Mannem HC, Kron IL, Krupnick AS, Linden J; Adenosine A2A receptor agonist (regadenoson) in human lung transplantation; J Heart Lung Transplant 2020; 39: 563-570; CRM
- Slingluff CL Jr, Petroni GR, Chianese-Bullock KA, Wages NA, Olson WC, Smith KT, Haden K, Dengel LT, Dickinson A, Reed C, Gaughan EM, Grosh WW, Kaur V, Varhegyi N, Smolkin M, Galeassi NV, Deacon D, Hall EH; Trial to evaluate the immunogenicity and safety of a melanoma helper peptide vaccine plus incomplete Freund’s adjuvant, cyclophosphamide, and polyICLC (Mel 63); Immunother Cancer 2021; [epub ahead of print] Jan 21; Design details
- Patel SP, Petroni GR, Roszik J, Olson WC, Wages NA, Chianese-Bullock KA, Smolkin M, Varhegyi N, Gaughan E, Smith KT, Haden K, Hall EH, Gnjatic S, Hwu P, Slingluff CL; Phase I/II trial of a long peptide vaccine (LPV7) plus toll-like receptor (TLR) agonists with or without incomplete Freund’s adjuvant (IFA) for resected high-risk melanoma (Mel 60); J Immunother Cancer. 2021 Aug; 9(8):e003220; Design details
- Portell CA, Wages NA, Kahl BS, Budde LE, Chen RW, Cohen JB, Varhegyi NE, Petroni GR, Williams ME; Dose-finding study of ibrutinib and venetoclax in relapsed or refractory mantle cell lymphoma; Blood Adv. 2022 Mar 8; 6(5):1490-1498; Design details