Lars Wagner

Overview:

I am a pediatric oncologist with a clinical and research focus on the care of adolescents and young adults with sarcoma. I have led multiple institutional and national clinical trials exploring new therapies for patients with recurrent sarcoma, and am interested in new drug development and identification of predictive biomarkers.

Positions:

Professor of Pediatrics

Pediatrics, Hematology-Oncology
School of Medicine

Chief, Division of Hematology/Oncology

Pediatrics, Hematology-Oncology
School of Medicine

Member of the Duke Cancer Institute of the

Duke Cancer Institute
School of Medicine

Education:

M.D. 1991

University of Kentucky, College of Medicine

Residency, Pediatrics

University of Tennessee Health Science Center

Hematology/Oncology Fellowship, St Jude Children's Hospital

University of Tennessee Health Science Center

Grants:

Per Case Reimbursement : NIH National Clinical Trials Network (NCTN)

Administered By
Pediatrics, Hematology-Oncology
Awarded By
Children's Hospital of Philadelphia
Role
Principal Investigator
Start Date
End Date

A Multi-Center Phase III, Randomized, Open-Label Trial of Vigil (bi-shRNAfurin and GMCSF Augmented Autologous Tumor Cell Immunotherapy) in combination with Irinotecan and Temozolomide as a Second-Line Regimen for Ewing's Sarcoma (CL-PTL-130)

Administered By
Pediatrics, Hematology-Oncology
Awarded By
Gradalis, Inc.
Role
Principal Investigator
Start Date
End Date

Workload Intensity NIH National Clinical Trials Network (NCTN)

Administered By
Pediatrics, Hematology-Oncology
Awarded By
Children's Hospital of Philadelphia
Role
Principal Investigator
Start Date
End Date

NCI Community Oncology Research Program (NCORP) Research Base Grant

Administered By
Pediatrics, Hematology-Oncology
Awarded By
Children's Hospital of Philadelphia
Role
Principal Investigator
Start Date
End Date

Project: One Time EOY, Integrated BIQSFP AAML1031- Echocardiogram Reports and Images

Administered By
Pediatrics, Hematology-Oncology
Awarded By
Children's Hospital of Philadelphia
Role
Principal Investigator
Start Date
End Date

Publications:

Receptor tyrosine kinase inhibitors for the treatment of osteosarcoma and Ewing sarcoma.

Adjuvant chemotherapy for osteosarcoma and Ewing sarcoma consists of conventional cytotoxic regimens that have changed little over the past decades. There is an urgent need for agents that are more effective and have less long-term toxicity. Receptor tyrosine kinases regulate cell growth and proliferation of these tumors, and small-molecule inhibitors for many of these kinases are now available. In this article, we review published phase II trials for patients with recurrent disease and highlight the pathways targeted by available agents, as well as the toxicity and efficacy results seen to date. We also discuss the difficulties in identifying biomarkers to facilitate rational patient selection, as well as published and proposed strategies for how these inhibitors can be combined with conventional chemotherapy or other targeted agents. It is hoped future trials can capitalize on this growing experience to optimize the use of this exciting class of agents.
Authors
MLA Citation
Just, Marissa A., et al. “Receptor tyrosine kinase inhibitors for the treatment of osteosarcoma and Ewing sarcoma.Pediatr Blood Cancer, vol. 68, no. 8, Aug. 2021, p. e29084. Pubmed, doi:10.1002/pbc.29084.
URI
https://scholars.duke.edu/individual/pub1482407
PMID
33894051
Source
pubmed
Published In
Pediatr Blood Cancer
Volume
68
Published Date
Start Page
e29084
DOI
10.1002/pbc.29084

Pursuing precision: Receptor tyrosine kinase inhibitors for treatment of pediatric solid tumors

Receptor tyrosine kinases are critical for the growth and proliferation of many different cancers and therefore represent a potential vulnerability that can be therapeutically exploited with small molecule inhibitors. Over forty small molecule inhibitors are currently approved for the treatment of adult solid tumors. Their use has been more limited in pediatric solid tumors, although an increasing number of single-agent and combination studies are now being performed. These agents have been quite successful in certain clinical contexts, such as the treatment of pediatric tumors driven by kinase fusions or activating mutations. By contrast, only modest activity has been ob-served when inhibitors are used as single agents for solid tumors that do not have genetically defined alterations in the target genes. The absence of predictive biomarkers has limited the wider applicability of these drugs and much work remains to define the appropriate patient population and clinical situation in which receptor tyrosine kinase inhibitors are most beneficial. In this manu-script, we discuss these issues by highlighting past trials and identifying future strategies that may help add precision to the use of these agents for pediatric extracranial solid tumors.
Authors
Bellantoni, AJ; Wagner, LM
MLA Citation
Bellantoni, A. J., and L. M. Wagner. “Pursuing precision: Receptor tyrosine kinase inhibitors for treatment of pediatric solid tumors.” Cancers, vol. 13, no. 14, July 2021. Scopus, doi:10.3390/cancers13143531.
URI
https://scholars.duke.edu/individual/pub1490070
Source
scopus
Published In
Cancers
Volume
13
Published Date
DOI
10.3390/cancers13143531

A PILOT CLINICAL TRIAL OF OROTECAN (VAL-413), A NOVEL ORAL DOSAGE FORMULATION OF IRINOTECAN: IMPLICATIONS FOR PEDIATRIC BRAIN TUMORS

Authors
Brown, D; Bacha, J; Wagner, L; Leggas, M; Kanekal, S; Lopez, L; Sankar, N
MLA Citation
URI
https://scholars.duke.edu/individual/pub1468000
Source
wos-lite
Published In
Neuro Oncology
Volume
22
Published Date
Start Page
60
End Page
60

Imaging of childhood urologic cancers: Current approaches and new advances

Urologic tumors make up approximately 10% of all pediatric cancers, and include a variety of different histologies and imaging considerations. In this review, we discuss standard radiologic approaches for children with tumors arising in the genitourinary system, and identify important ways in which imaging affects the differential diagnosis, preoperative planning, and staging of these tumors. In addition, we provide an update on strategies to reduce the time of imaging, which may obviate the need for sedation in younger patients. Efforts to reduce a patient's overall radiation exposure and subsequent risk of second malignancy are also detailed, including recent work on surveillance imaging following completion of therapy. Finally, we highlight new techniques such as radiomics that are now being investigated for patients with these malignancies.
Authors
Davis, JT; Wagner, LM
MLA Citation
Davis, J. T., and L. M. Wagner. “Imaging of childhood urologic cancers: Current approaches and new advances.” Translational Andrology and Urology, vol. 9, no. 5, Oct. 2020, pp. 2348–57. Scopus, doi:10.21037/tau-19-839.
URI
https://scholars.duke.edu/individual/pub1465821
Source
scopus
Published In
Translational Andrology and Urology
Volume
9
Published Date
Start Page
2348
End Page
2357
DOI
10.21037/tau-19-839

Phase II trial of gemcitabine and nab-paclitaxel in patients with recurrent Ewing sarcoma: A report from the National Pediatric Cancer Foundation.

BACKGROUND: The combination of gemcitabine and docetaxel is often used to treat patients with recurrent sarcoma. Nab-paclitaxel is a taxane modified to improve drug exposure and increase intratumoral accumulation and, in combination with gemcitabine, is standard therapy for pancreatic cancer. Applying the dosages and schedule used for pancreatic cancer, we performed a phase II trial to assess the response rate of gemcitabine and nab-paclitaxel in patients with relapsed Ewing sarcoma. PROCEDURE: Using a Simon's two-stage design to identify a response rate of ≥ 35%, patients received nab-paclitaxel 125 mg/m2 followed by gemcitabine 1000 mg/m2 i.v. on days 1, 8, and 15 of four-week cycles. Immunohistochemical analysis of archival tissue was performed to identify possible biomarkers of response. RESULTS: Eleven patients from four institutions enrolled, with a median age of 22 years (range, 14-27). Patients were heavily pretreated (median 3 prior regimens, range, 1-7). Thirty-five cycles were administered (median 2, range, 1-8). Accrual was stopped after 11 patients, due to only one confirmed partial response. Two other patients had partial responses after two cycles, but withdrew because of adverse effects or progression before confirmation of continued response. The predominant toxicity was myelosuppression, and four (36%) patients were removed due to hematologic toxicity despite pegfilgrastim and dose reductions. Expression of secreted protein, acidic and rich in cysteine (SPARC) and CAV-1 in archival tumors was not predictive of clinical benefit in this small cohort of patients. CONCLUSIONS: In patients with heavily pretreated Ewing sarcoma, the confirmed response rate of 9% was similar to multi-institutional studies of gemcitabine and docetaxel.
Authors
Oesterheld, JE; Reed, DR; Setty, BA; Isakoff, MS; Thompson, P; Yin, H; Hayashi, M; Loeb, DM; Smith, T; Makanji, R; Fridley, BL; Wagner, LM
MLA Citation
Oesterheld, Javier E., et al. “Phase II trial of gemcitabine and nab-paclitaxel in patients with recurrent Ewing sarcoma: A report from the National Pediatric Cancer Foundation.Pediatr Blood Cancer, vol. 67, no. 7, July 2020, p. e28370. Pubmed, doi:10.1002/pbc.28370.
URI
https://scholars.duke.edu/individual/pub1441386
PMID
32386107
Source
pubmed
Published In
Pediatr Blood Cancer
Volume
67
Published Date
Start Page
e28370
DOI
10.1002/pbc.28370