Over the past 15 years Dr. Schipper has collaborated with medical researchers in a wide variety of therapeutic areas with a focus on oncology, biomarkers and early phase clinical trials. He has extensive experience in modeling outcomes in radio-immunotherapy and oncology. His methodological research interests are in predictive risk modeling, use of biomarkers to individualize and adapt cancer treatment and early phase oncology study design. He has authored or co-authored more than 90 papers published in peer-reviewed journals.
Selection of dose for cancer patients treated with Radiation Therapy (RT) must balance the increased efficacy with the increased toxicity associated with higher dose. Historically, a single dose has been selected for a population of patients (e.g. all stage III NSC lung cancer). However, the availability of new biologic markers for toxicity and efficacy allow the possibility of selecting a more personalized dose. Dr. Schipper is working on a Utility based method that uses statistical models for toxicity and efficacy as a function of RT dose and biomarkers to select an optimal dose for an individual patient. With his collaborators, he is studying quantitative methods for making this efficacy/toxicity tradeoff explicit when biomarkers for one or both outcomes are available. They have proposed a simulation based method for studying the likely effects of any model or marker based dose selection on both toxicity and efficacy outcomes for a population of patients. In related projects, Dr Schipper is studying the role of correlation between the sensitivity of a patient' tumor and normal tissues to radiation and how to utilize these techniques in combination with baseline and/or mid-treatment adaptive image guided RT.
An increasingly common feature of phase I designs is the inclusion of 1 or more dose expansion cohorts (DECs) in which the maximum tolerated dose (MTD) is first estimated using a 3+3 or other Phase I design and then a fixed number (often 10-20 in 1-10 cohorts) of patients are treated at the dose initially estimated to be the MTD. Such an approach has not been studied statistically or compared to alternative designs. Dr. Schipper and colleagues have shown that a CRM design, in which the dose-assignment mechanism is kept active for all patients, more accurately identifies the MTD and better protects the safety of trial patients than a similarly sized DEC trial. It also meets the objective of treating 15 or more patients at the final estimated MTD. A follow-up paper evaluating the role of DECs with a focus on efficacy estimation is in press at Annals of Oncology.
Areas of Interest
- Use of biomarkers to individualize treatment
- Early phase oncology study design
- PhD, University of Michigan, 2006
- 5 R01 EB022075-04 (PI: Dewaraja), 09/2016-06/2017, National Institutes of Health: Imaging and dosimetry of yttrium-90 for personalized cancer treatment, Role: Co-Investigator with Effort.
- 3 P50 CA130810-05S2, (PI: Brenner), 09/2016-08/2017, National Institutes of Health: Translational research in GI cancer: Interim Funding , Role: Co-Investigator with Effort.
- 5 R01 CA184153-05m,(PI: Eisbruch/Cao), 03/2015-02/2020, National Institutes of Health: Functional imaging-directed adaptive therapy of head and neck cancer, Role: Co-Investigator with Effort.
- (PI: Feng), 07/2014-06/2019, Varian Medical Systems,: A phase II randomized trial comparing stereotactic body radiation therapy to radiofrequency ablation for the treatment of renal cell carcinoma, Role: Co-I with Effort.
- 5 U01 CA183848-05 (PI: Cao/Eisbruch), 04/2014-03/2019, National Instituetes of Health: Quantitative MRI models of HN cancers for physiological adaption of RT , Role: Co-Investigator with Effort.
- 4 P30 CA046592-28 (PI: Fearon), 09/2011-05/2017, National Institutes of Health: University of Michigan Cancer Center Support Grant , Role: Co-Investigator with Effort.
- R01 CA160981 (PI: Ray), 09/2011-07/2017, National Institutes of Health: Targeting SMURF2 as a novel therapy for EGFR driven tumors, Role: Co-Investigator.
- 5 P01 CA059827-20 (PIs: Lawrence/TenHaken), 07/2006-04/2019, National Institutes of Health: Optimization of high dose conformal therapy, Role: Co-Investigator with Effort.
Selected from over 100 publications
- Schipper MJ, Taylor JMG, TenHaken R, Matuzak M, Kong F and Lawrence TS. Personalized dose selection in Radiation Therapy using statistical models for toxicity and efficacy with dose and biomarkers as covariates. Stat Med, 33(30): 5330-9, 2014.
- Boonstra PS, Shen J, Taylor JM, Braun TM, Griffith KA, Daignault S, Kalemkerian GP, Lawrence TS, Schipper MJ: A statistical evaluation of dose expansion cohorts in phase I clinical trials. J Natl Cancer Inst, 107(3): pii: dju429, 2015. PM25710960
- Wahl DR, Stenmark MH, Tao Y, Pollom EL, Caoili EM, Lawrence TS, Schipper MJ, Feng M: Outcomes after stereotactic body radiotherapy or radiofrequency ablation for hepatocellular carcinoma. J ClinOncol, 34(5): 452-9, 2016. PM26628466/PMC48720
- Dess R, Sun Y, ... Schipper MJ, Jolly S. Cardiac events and dose escalated radiotherapy: Combined analysis of prospective multicenter trials for locally advanced non-small cell lung cancer, J Clin Oncol (accepted): 2017. (In Press).
- Boonstra PS, Braun TM, Taylor JMG, Kidwell K, Zhao L, Daignault SD, Griffith KA, Lawrence TS, Kalemkerian GP and Schipper MJ. Statistical Controversies In Cancer Research: Building the bridge to phase II: Efficacy estimation in dose-expansion cohorts. Ann Oncol (Accepted): 2017. (In Press).