Hope Uronis

Positions:

Associate Professor of Medicine

Medicine, Medical Oncology
School of Medicine

Member of the Duke Cancer Institute

Duke Cancer Institute
School of Medicine

Education:

M.D. 2000

State University of New York at Buffalo

Medical Resident, Medicine

Duke University

Fellow in Hematology-Oncology, Medicine

Duke University

Chief Medical Resident -Duke Hospital, Medicine

Duke University

Fellow in Hematology-Oncology, Medicine

Duke University

Grants:

MK 3475 - PN811

Administered By
Duke Cancer Institute
Role
Principal Investigator
Start Date
End Date

A Randomized multicenter double blind Phase III study of Nivolumab or placebo in subjects with resected esophageal junction cancer.

Administered By
Duke Cancer Institute
Role
Principal Investigator
Start Date
End Date

A Multicenter randomized open label study in patients with esophageal cancer refractory or intorlerant to combination therapy with fluoropyrimidine

Administered By
Duke Cancer Institute
Role
Principal Investigator
Start Date
End Date

A Phase 1b/2 open label dose escalation study of Margetuximab incombination with Pembrolizumab in patients with relapsed refrectory advanced HER2 + Gastroesophageal junction or gastric cancer.

Administered By
Duke Cancer Institute
Role
Principal Investigator
Start Date
End Date

Key LARGO: PII

Administered By
Duke Cancer Institute
Role
Principal Investigator
Start Date
End Date

Publications:

Safety at the Time of the COVID-19 Pandemic: How to Keep our Oncology Patients and Healthcare Workers Safe.

The novel coronavirus, SARS-CoV-2, was first detected as a respiratory illness in December 2019 in Wuhan City, China. Since then, coronavirus disease 2019 (COVID-19) has impacted every aspect of our lives worldwide. In a time when terms such as social distancing and flattening the curve have become a part of our vernacular, it is essential that we understand what measures can be implemented to protect our patients and healthcare workers. Undoubtedly, healthcare providers have had to rapidly alter care delivery models while simultaneously acknowledging the crucial unknowns of how these changes may affect clinical outcomes. This special feature reviews strategies on how to mitigate transmission of COVID-19 in an effort to reduce morbidity and mortality associated with the disease for patients with cancer without infection, for patients with cancer with COVID-19 infection, and for the healthcare workers caring for them, while continuing to provide the best possible cancer care. [Editor's Note: This article includes the most current information available at time of publication; however, recommendations regarding public safety and practice may change rapidly in this situation. Individuals should get the most up to date information from the CDC website.].
Authors
Cinar, P; Kubal, T; Freifeld, A; Mishra, A; Shulman, L; Bachman, J; Fonseca, R; Uronis, H; Klemanski, D; Slusser, K; Lunning, M; Liu, C
MLA Citation
Cinar, Pelin, et al. “Safety at the Time of the COVID-19 Pandemic: How to Keep our Oncology Patients and Healthcare Workers Safe.Journal of the National Comprehensive Cancer Network : Jnccn, Apr. 2020, pp. 1–6. Epmc, doi:10.6004/jnccn.2020.7572.
URI
https://scholars.duke.edu/individual/pub1438557
PMID
32294617
Source
epmc
Published In
Jnccn Journal of the National Comprehensive Cancer Network
Published Date
Start Page
1
End Page
6
DOI
10.6004/jnccn.2020.7572

A phase Ib study of capecitabine and ziv-aflibercept followed by a phase II single-arm expansion cohort in chemotherapy refractory metastatic colorectal cancer.

BACKGROUND: Patients with chemotherapy refractory metastatic colorectal cancer (CRC) have a poor prognosis and limited therapeutic options. In this phase Ib/II clinical trial, we established the maximum tolerated dose (MTD) and recommended phase II dose (RPTD) for the combination of capecitabine and ziv-aflibercept, and then we evaluated the efficacy of the combination in patients with chemotherapy refractory metastatic CRC. METHODS: All patients were required to have a Karnofsky Performance Status > 70% and adequate organ function. The phase Ib dose escalation cohort included patients with advanced solid tumors who had progressed on all standard therapies. Using a standard 3 + 3 design, we identified the MTD and RPTD for the combination. Fifty patients with metastatic CRC who had progressed on or were intolerant of a fluoropyrimidine, oxaliplatin, irinotecan, and bevacizumab were then enrolled in a single-arm phase II expansion cohort, and were treated at the RPTD. Prior EGFR antibody therapy was required for subjects with RAS wildtype tumors. The primary endpoint for the expansion cohort was progression-free survival (PFS) at two months. Secondary endpoints included objective response rate (ORR) and overall survival (OS). RESULTS: A total of 63 patients were enrolled and evaluable for toxicity (13 dose escalation; 50 expansion). The MTD and RPTD were: capecitabine 850 mg/m2, P.O. bid, days 1-14, and ziv-aflibercept 6 mg/kg I.V., day 1, of each 21-day cycle. In the expansion cohort, 72% of patients were progression-free at two months (95% confidence interval [CI], 60-84%). Median PFS and OS were 3.9 months (95% CI, 2.3-4.5) and 7.1 months (95% CI: 5.8-10.0), respectively. Among all patients evaluable for toxicity, the most common treatment related adverse events (all grade [%]; grade ≥ 3 [%]) included palmar-plantar erythrodysesthesia (41%; 6%), hypertension (33%; 22%), and mucositis (19%; 5%). RNA was isolated from archived tumor specimens and gene expression analyses revealed no association between angiogenic biomarkers and clinical outcomes. CONCLUSION: The combination of capecitabine and ziv-aflibercept at the RPTD demonstrated acceptable safety and tolerability. PFS at 2 months in patients with chemotherapy refractory metastatic CRC was significantly greater than that in historical controls, indicating that this combination warrants further study. TRIAL REGISTRATION: This clinical trial was registered in the www.clinicaltrials.gov system as NCT01661972 on July 31, 2012.
Authors
Strickler, JH; Rushing, CN; Niedzwiecki, D; McLeod, A; Altomare, I; Uronis, HE; Hsu, SD; Zafar, SY; Morse, MA; Chang, DZ; Wells, JL; Blackwell, KL; Marcom, PK; Arrowood, C; Bolch, E; Haley, S; Rangwala, FA; Hatch, AJ; Nixon, AB; Hurwitz, HI
MLA Citation
Strickler, John H., et al. “A phase Ib study of capecitabine and ziv-aflibercept followed by a phase II single-arm expansion cohort in chemotherapy refractory metastatic colorectal cancer.Bmc Cancer, vol. 19, no. 1, Nov. 2019, p. 1032. Pubmed, doi:10.1186/s12885-019-6234-8.
URI
https://scholars.duke.edu/individual/pub1417915
PMID
31675952
Source
pubmed
Published In
Bmc Cancer
Volume
19
Published Date
Start Page
1032
DOI
10.1186/s12885-019-6234-8

A phase Ib study of the combination regorafenib with PF-03446962 in patients with refractory metastatic colorectal cancer (REGAL-1 trial).

PURPOSE: This study aimed to evaluate the maximum tolerated dose (MTD) and recommended phase II dose (RPTD), as well as the safety and tolerability of PF-03446962, a monoclonal antibody targeting activin receptor like kinase 1 (ALK-1), in combination with regorafenib in patients with refractory metastatic colorectal cancer. METHODS: The first stage of this study was a standard "3 + 3" open-label dose-escalation scheme. Cohorts of 3-6 subjects were started with 120 mg of regorafenib given PO daily for 3 weeks of a 4 week cycle, plus 4.5 mg/kg of PF-03446962 given IV every 2 weeks. Doses of both drugs were adjusted according to dose-limiting toxicities (DLT). Plasma was collected for multiplexed ELISA analysis of factors related to tumor growth and angiogenesis. RESULTS: Seventeen subjects were enrolled, of whom 11 were deemed evaluable. Seven subjects were enrolled at dose level 1, and four were enrolled at level - 1. Overall, three DLTs were observed during the dose-escalation phase: two in level 1 and one in level - 1. A planned dose-expansion cohort was not started due to early termination of the clinical trial. Common adverse events were infusion-related reaction, fatigue, palmar-plantar erythrodysesthesia syndrome, abdominal pain, dehydration, nausea, back pain, anorexia, and diarrhea. One subject achieved stable disease for 5.5 months, but discontinued treatment due to adverse events. CONCLUSIONS: The regimen of regorafenib and PF-03446962 was associated with unacceptable toxicity and did not demonstrate notable clinical activity in patients with refractory metastatic colorectal cancer.
Authors
Clarke, JM; Blobe, GC; Strickler, JH; Uronis, HE; Zafar, SY; Morse, M; Dropkin, E; Howard, L; O'Neill, M; Rushing, CN; Niedzwiecki, D; Watson, H; Bolch, E; Arrowood, C; Liu, Y; Nixon, AB; Hurwitz, HI
MLA Citation
Clarke, Jeffrey Melson, et al. “A phase Ib study of the combination regorafenib with PF-03446962 in patients with refractory metastatic colorectal cancer (REGAL-1 trial).Cancer Chemother Pharmacol, vol. 84, no. 4, Oct. 2019, pp. 909–17. Pubmed, doi:10.1007/s00280-019-03916-0.
URI
https://scholars.duke.edu/individual/pub1405169
PMID
31444620
Source
pubmed
Published In
Cancer Chemother Pharmacol
Volume
84
Published Date
Start Page
909
End Page
917
DOI
10.1007/s00280-019-03916-0

A phase 1b/2, open label, dose-escalation study of margetuximab (M) in combination with pembrolizumab (P) in patients with relapsed/refractory advanced HER2+ gastroesophageal (GEJ) junction or gastric (G) cancer.

<jats:p> TPS219 </jats:p><jats:p> Background: Prognosis for advanced HER2+ GEJ and G cancers remains poor, with median survival just beyond one year. Trastuzumab (T) in combination with chemotherapy is the initial treatment of choice, but therapeutic options targeting HER2 beyond T are poorly defined. M is an Fc-enhanced monoclonal antibody (Mab) to HER2 that recognizes with similar affinity the same epitope as T and whose Fc domain, compared to T, binds with increased affinity to the activating CD16A Fc-receptor (FcR) and decreased affinity to the inhibitory CD32B FcR. Preliminary data shows that M monotherapy has clinical activity against HER2+ tumors in GEJ and G cancer patients previously treated with T or other anti-HER2 agents. P is a Mab that blocks the interaction of the immune checkpoint molecule, PD-1, with its ligands, facilitating tumor cell elimination by releasing tumor-associated T cells from exhaustion. Monotherapy P has demonstrated remarkable and durable clinical activity in a Phase I study. Safety profiles of M and P are acceptable and non-overlapping. Methods: This study advances a chemotherapy free combination of M + P treatment for advanced HER2+ GEJ and G cancer patients. Enrolled patients will have relapsed/refractory HER2+ GEJ or G adenocarcinoma with measurable disease that has progressed on T plus first line chemotherapy. HER2+ (IHC 3+ or ISH+) will be confirmed by central review. Two dose levels of M (10mg/kg and 15mg/kg) and a fixed dose of P (200mg) will be evaluated for safety and tolerability. Patients will receive combination treatment once every 21 days for up to 24 months, until confirmed disease progression or intolerable toxicity. Dose expansion will enroll up to 60 patients, with 20 undergoing pre- and on-treatment biopsy. Response will be assessed every 6 weeks for the first 6 months and every 12 weeks thereafter per RECIST v1.1 and immune RECIST to account for response patterns observed with immunotherapies. Primary endpoint is ORR and duration of response, and secondary endpoints include PFS and OS. The study was initiated on January 2016 and is ongoing in North America and Asia. Clinical trial information: NCT02689284. </jats:p>
Authors
Catenacci, DVT; Kim, SS; Gold, PJ; Philip, PA; Enzinger, PC; Coffie, J; Schmidt, EV; Baldwin, M; Nordstrom, JL; Bonvini, E; Wigginton, JM; Hochster, HS; Denlinger, CS; Uronis, HE; Bendell, JC; Kelly, RJ; Davidson-Moncada, JK; Lockhart, AC
MLA Citation
Catenacci, Daniel V. T., et al. “A phase 1b/2, open label, dose-escalation study of margetuximab (M) in combination with pembrolizumab (P) in patients with relapsed/refractory advanced HER2+ gastroesophageal (GEJ) junction or gastric (G) cancer.Journal of Clinical Oncology, vol. 35, no. 4_suppl, American Society of Clinical Oncology (ASCO), 2017, pp. TPS219–TPS219. Crossref, doi:10.1200/jco.2017.35.4_suppl.tps219.
URI
https://scholars.duke.edu/individual/pub1367224
Source
crossref
Published In
Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology
Volume
35
Published Date
Start Page
TPS219
End Page
TPS219
DOI
10.1200/jco.2017.35.4_suppl.tps219

Phase I study of dasatinib in combination with capecitabine, oxaliplatin and bevacizumab followed by an expanded cohort in previously untreated metastatic colorectal cancer.

PURPOSE: Dasatinib inhibits src family kinases and has anti-angiogenic properties. We conducted a phase I study of dasatinib, capecitabine, oxaliplatin, and bevacizumab (CapeOx/bevacizumab), with an expansion cohort in metastatic colorectal cancer (CRC). METHODS: Patients were enrolled in a dose escalation cohort to establish the maximum tolerated dose (MTD) and the recommended phase II dose (RP2D). Using a "3 + 3" design, twelve patients with advanced solid tumors received dasatinib (50 mg twice daily or 70 mg daily), capecitabine (850 mg/m(2) twice daily, days 1-14), oxaliplatin (130 mg/m(2) on day 1) and bevacizumab (7.5 mg/kg on day1), every 3 weeks. Ten patients with previously untreated metastatic CRC were then enrolled in an expansion cohort. Activated src (src(act)) expression was measured by immunohistochemistry, using an antibody that selectively recognizes the active conformation of src (clone 28). RESULTS: Twenty-two patients were enrolled between June 2009 and May 2011. Two DLTs were observed in the 50 mg bid dasatinib cohort, and one DLT was observed in the 70 mg daily dasatinib cohort. The MTD and RP2D for dasatinib was 70 mg daily. The most common treatment-related adverse events were fatigue (20; 91 %) and diarrhea (18; 82 %). Biomarker analysis of src(act) expression demonstrated that the overall response rate (ORR) was 75 % (6/8) for patients with high src(act) expression (IHC ≥ 2), compared to 0 % (0/8) for patients with low srcact expression (IHC 0 or 1); (p = 0.007). CONCLUSIONS: The RP2D of dasatinib is 70 mg daily in combination with CapeOx/bevacizumab. High levels of srcact expression may predict those patients most likely to benefit from dasatinib.
Authors
Strickler, JH; McCall, S; Nixon, AB; Brady, JC; Pang, H; Rushing, C; Cohn, A; Starodub, A; Arrowood, C; Haley, S; Meadows, KL; Morse, MA; Uronis, HE; Blobe, GC; Hsu, SD; Zafar, SY; Hurwitz, HI
MLA Citation
Strickler, John H., et al. “Phase I study of dasatinib in combination with capecitabine, oxaliplatin and bevacizumab followed by an expanded cohort in previously untreated metastatic colorectal cancer.Invest New Drugs, vol. 32, no. 2, Apr. 2014, pp. 330–39. Pubmed, doi:10.1007/s10637-013-0042-9.
URI
https://scholars.duke.edu/individual/pub967259
PMID
24173967
Source
pubmed
Published In
Invest New Drugs
Volume
32
Published Date
Start Page
330
End Page
339
DOI
10.1007/s10637-013-0042-9

Research Areas:

Adenocarcinoma
Administration, Oral
Adult
Aged
Aged, 80 and over
Ampulla of Vater
Anastomotic Leak
Angiogenesis Inhibitors
Aniline Compounds
Anoxia
Antibodies, Monoclonal
Antibodies, Monoclonal, Humanized
Antineoplastic Combined Chemotherapy Protocols
Anus Neoplasms
Anxiety
Bevacizumab
Carcinoma, Squamous Cell
Chemoradiotherapy
Chemoradiotherapy, Adjuvant
Colorectal Neoplasms
Combined Modality Therapy
Common Bile Duct Neoplasms
Depression
Esophagectomy
Female
Follow-Up Studies
Gastrointestinal Neoplasms
Humans
Hydroxamic Acids
Hypocalcemia
Hypokalemia
Hypoxia
Immunosuppressive Agents
Injections, Intravenous
Kaplan-Meier Estimate
Language
Leukocytes, Mononuclear
Liver Neoplasms
Lymph Nodes
Lymphatic Irradiation
Male
Middle Aged
Models, Statistical
Neoadjuvant Therapy
Neoplasm Recurrence, Local
Organoplatinum Compounds
Oxaliplatin
Pain Measurement
Palliative Care
Pancreatic Neoplasms
Patient Satisfaction
Photons
Platinum Compounds
Protein Kinase Inhibitors
Psychometrics
Pyrimidines
Quality of Life
Randomized Controlled Trials as Topic
Regression Analysis
Reproducibility of Results
Retrospective Studies
Risk Factors
Sirolimus
Socioeconomic Factors
Sulfonamides
Survival Rate
Thiazoles
Tumor Markers, Biological
Young Adult