Jeffrey Crawford

Overview:

1. Lung cancer/new treatment approaches.
2. Clinical trials of hematopoietic growth factors, biological agents and targeted drug development.
3. Cancer in the elderly and supportive care

Accomplishments

1. Lead Investigator of the U. S. multicenter, randomized trial of Filgrastim (G-CSF, Neupogen) to reduce the morbidity of chemotherapy-related neutropenia, leading to FDA approval 2/91.
2. Lead Investigator of the U. S. multicenter, randomized trial of Vinorelbine (Navelbine) in treatment of patients with advanced non small cell carcinoma of lung (NSCLC), leading to FDA approval 12/94.
3. Principal Investigator in initial phase I clinical trials of stem cell factor (SCF), megakaryocyte growth and development factor (MGDF), pegylated granulocyte-colony-stimulating factor and other novel hematopoietic growth factors.

Positions:

George Barth Geller Distinguished Professor of Immunology

Medicine, Medical Oncology
School of Medicine

Professor of Medicine

Medicine, Medical Oncology
School of Medicine

Member of the Duke Cancer Institute

Duke Cancer Institute
School of Medicine

Education:

M.D. 1974

Ohio State University

Grants:

A PHASE III PROSPECTIVE DOUBLE BLIND PLACEBO CONTROLLED RANDOMIZED STUDY OF ADJUVANT MEDI4736 IN COMPLETELY RESECTED NON-SMALL CELL LUNG CANCER

Administered By
Duke Cancer Institute
Awarded By
Clinipace, Inc.
Role
Principal Investigator
Start Date
End Date

PHASE 3, RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED, MULTICENTER STUDY TO EVALUATE THE EFFICACY AND SAFETY OF ANAMORELIN HCL

Administered By
Duke Cancer Institute
Awarded By
Helsinn Healthcare S.A.
Role
Principal Investigator
Start Date
End Date

A phase II, Open-label, single-arm study to assess the safety and efficacy of AZD9291 in patients with locally advanced/mteastatic non-small cell lung cancer whose disease has progressed with previous epidermal growth factor receptor

Administered By
Duke Cancer Institute
Awarded By
AstraZeneca AB
Role
Principal Investigator
Start Date
End Date

Phase II anetumab ravtansine as 2nd line treatment for malignant pleural mesothelioma

Administered By
Duke Cancer Institute
Awarded By
Bayer HealthCare AG
Role
Principal Investigator
Start Date
End Date

EMD Serono, Inc. Education Event

Administered By
Medicine, Medical Oncology
Awarded By
EMD Serono Inc
Role
Principal Investigator
Start Date
End Date

Publications:

Osimertinib for Patients With Leptomeningeal Metastases Associated With EGFR T790M-Positive Advanced NSCLC: The AURA Leptomeningeal Metastases Analysis.

INTRODUCTION: Osimertinib has shown promising activity in patients with leptomeningeal metastases (LMs) of EGFR-positive NSCLC at 160 mg once daily (qd) (BLOOM; NCT02228369). We report LM activity with osimertinib (80 mg qd) in a retrospective analysis of studies across the AURA program (AURA extension, AURA2, AURA17, and AURA3). METHODS: Patients with EGFR T790M-positive advanced NSCLC and progression after previous EGFR-tyrosine kinase inhibitor therapy received osimertinib (80 mg qd). Patients with central nervous system (CNS) metastases (including LMs) were eligible if the lesions were neurologically asymptomatic and stable. Patients with evidence of LMs at the study entry were retrospectively included for the analysis; brain scans were assessed for radiologic LM response by neuroradiologically blinded, independent central review per the modified Response Assessment in Neuro-Oncology LM criteria. LM objective response rate, duration of response, progression-free survival, and overall survival were assessed. A longitudinal analysis was performed to investigate the relationship between changes from the baseline in non-CNS tumor sizes and LM responses at each visit of patients in AURA LM and BLOOM studies. RESULTS: For the 22 patients included in the analysis, LM objective response rate was 55% (95% confidence interval [CI]: 32-76). Median LM duration of response was not reached (95% CI: 2.8-not calculable [NC]). Median LM progression-free survival and overall survival were 11.1 months (95% CI: 4.6-NC) and 18.8 months (95% CI: 6.3-NC), respectively. The longitudinal analysis revealed similar non-CNS and LM responses between the patients in AURA LM and BLOOM programs. CONCLUSIONS: Patients with EGFR T790M-positive NSCLC and radiologically detected LM obtained clinical benefit from osimertinib (80 mg qd).
Authors
Ahn, M-J; Chiu, C-H; Cheng, Y; Han, J-Y; Goldberg, SB; Greystoke, A; Crawford, J; Zhao, Y; Huang, X; Johnson, M; Vishwanathan, K; Yates, JWT; Brown, AP; Mendoza-Naranjo, A; Mok, T
MLA Citation
Ahn, Myung-Ju, et al. “Osimertinib for Patients With Leptomeningeal Metastases Associated With EGFR T790M-Positive Advanced NSCLC: The AURA Leptomeningeal Metastases Analysis.J Thorac Oncol, vol. 15, no. 4, Apr. 2020, pp. 637–48. Pubmed, doi:10.1016/j.jtho.2019.12.113.
URI
https://scholars.duke.edu/individual/pub1426996
PMID
31887431
Source
pubmed
Published In
J Thorac Oncol
Volume
15
Published Date
Start Page
637
End Page
648
DOI
10.1016/j.jtho.2019.12.113

Abstract OT1-05-01: The incidence of febrile neutropenia (FN) for chemotherapy patients receiving pegfilgrastim by an on-body injector (pegfilgrastim OBI) versus other FN prophylaxis strategies

Authors
Mahtani, R; Crawford, J; Rifkin, R; Dale, D; Brookhart, A; Gawade, P; Lawrence, T; Balani, R; Lyman, GH
MLA Citation
Mahtani, Reshma, et al. “Abstract OT1-05-01: The incidence of febrile neutropenia (FN) for chemotherapy patients receiving pegfilgrastim by an on-body injector (pegfilgrastim OBI) versus other FN prophylaxis strategies.” Ongoing Clinical Trials, American Association for Cancer Research, 2020. Crossref, doi:10.1158/1538-7445.sabcs19-ot1-05-01.
URI
https://scholars.duke.edu/individual/pub1443336
Source
crossref
Published In
Ongoing Clinical Trials
Published Date
DOI
10.1158/1538-7445.sabcs19-ot1-05-01

Sarcopenia: A Time for Action. An SCWD Position Paper.

The term sarcopenia was introduced in 1988. The original definition was a "muscle loss" of the appendicular muscle mass in the older people as measured by dual energy x-ray absorptiometry (DXA). In 2010, the definition was altered to be low muscle mass together with low muscle function and this was agreed upon as reported in a number of consensus papers. The Society of Sarcopenia, Cachexia and Wasting Disorders supports the recommendations of more recent consensus conferences, i.e. that rapid screening, such as with the SARC-F questionnaire, should be utilized with a formal diagnosis being made by measuring grip strength or chair stand together with DXA estimation of appendicular muscle mass (indexed for height2). Assessments of the utility of ultrasound and creatine dilution techniques are ongoing. Use of ultrasound may not be easily reproducible. Primary sarcopenia is aging associated (mediated) loss of muscle mass. Secondary sarcopenia (or disease-related sarcopenia) has predominantly focused on loss of muscle mass without the emphasis on muscle function. Diseases that can cause muscle wasting (i.e. secondary sarcopenia) include malignant cancer, COPD, heart failure, and renal failure and others. Management of sarcopenia should consist of resistance exercise in combination with a protein intake of 1 to 1.5 g/kg/day. There is insufficient evidence that vitamin D and anabolic steroids are beneficial. These recommendations apply to both primary (age-related) sarcopenia and secondary (disease related) sarcopenia. Secondary sarcopenia also needs appropriate treatment of the underlying disease. It is important that primary care health professionals become aware of and make the diagnosis of age-related and disease-related sarcopenia. It is important to address the risk factors for sarcopenia, particularly low physical activity and sedentary behavior in the general population, using a life-long approach. There is a need for more clinical research into the appropriate measurement for muscle mass and the management of sarcopenia. Accordingly, this position statement provides recommendations on the management of sarcopenia and how to progress the knowledge and recognition of sarcopenia.
Authors
Bauer, J; Morley, JE; Schols, AMWJ; Ferrucci, L; Cruz-Jentoft, AJ; Dent, E; Baracos, VE; Crawford, JA; Doehner, W; Heymsfield, SB; Jatoi, A; Kalantar-Zadeh, K; Lainscak, M; Landi, F; Laviano, A; Mancuso, M; Muscaritoli, M; Prado, CM; Strasser, F; von Haehling, S; Coats, AJS; Anker, SD
MLA Citation
Bauer, Juergen, et al. “Sarcopenia: A Time for Action. An SCWD Position Paper.J Cachexia Sarcopenia Muscle, vol. 10, no. 5, Oct. 2019, pp. 956–61. Pubmed, doi:10.1002/jcsm.12483.
URI
https://scholars.duke.edu/individual/pub1418503
PMID
31523937
Source
pubmed
Published In
J Cachexia Sarcopenia Muscle
Volume
10
Published Date
Start Page
956
End Page
961
DOI
10.1002/jcsm.12483

Molecular biology and treatment strategies for non-V600 BRAF-mutant NSCLC.

<jats:p> 3102 </jats:p><jats:p> Background: BRAF alterations (alts) account for ~4% of non-small cell lung cancers (NSCLC) with 50% being non-V600 alts. Because these alts are functionally heterogeneous and have a poorly characterized genomic landscape, determining appropriate treatment strategies is a challenge. Methods: The Guardant360 clinical database was queried for NSCLC patients (pts) with BRAF alts. Alts were categorized by clonality, type and class (1 and 2: BRAF monomer and dimer signaling; 3: requires co-occurring upstream RAS-mediated signaling). Functionality and drug screen assays were performed in Ba/F3 cells. Pts with non-V600 mutations were analyzed for sensitivity to MEK +/- BRAF inhibitors (M+Bi). Results: 306 unique BRAF alts were identified and the majority were observed once (233/306; 76%). Amplifications (806/1663; 48.5%) and missense alts (795/1663; 47.8%) were the most common occurrences. Missense alts were predominantly clonal (58%), and of known functionality (428/795; 54%). All class 1-2 alts were activating in Ba/F3 cells, while class 3 alts were found to have variable functionality (activating: 4/9). Functionality was correlated with clonality as demonstrated by class 1-3 alts having higher clonality compared to variants of unknown significance (VUS) (1: 56%; 2: 54%; 3: 45%; VUS: 38%; P&lt;0.01). Drug screens for G469V and L597R alts showed resistance to first generation BRAF inhibitors (IC50 ≥100nM), but sensitivity to M+Bi (IC50 0.02-36nM). Growth inhibition was more pronounced for dabrafenib + trametinib (D+T) (IC50 &lt;0.1nM) compared to encorafenib + binimetinib (IC50 8-35nM) and vemurafenib + cobimetinib (IC50 2-36nM). BRAF D594G mutation (class 3) was not activating in Ba/F3 cells. Three pts with non-V600 alts were treated with M+Bi. G469V and D594G had rapid disease progression (PFS 2 and 4 mos respectively), while pt with L597R has ongoing partial response (PFS 8+ mos). Conclusions: BRAF alts show correlation between clonality and functionality, which provides important clinical information given the numerous VUS in the BRAF non-V600 setting. Drug screens reveal non-V600 alts may be sensitive to M+Bi and suggest D+T is the most active combination. Clinical data supports that some non-V600 BRAF mutations may be sensitive to M+Bi. </jats:p>
Authors
Negrao, MV; Raymond, VM; Lanman, RB; Ng, PKS; Nagy, R; Banks, K; Zhu, VW; Amador, BE; Roarty, E; Chae, YK; Clarke, JM; Crawford, J; Ou, S-HI; Gandara, DR; Heymach, J; Bivona, TG; McCoach, CE
MLA Citation
Negrao, Marcelo Vailati, et al. “Molecular biology and treatment strategies for non-V600 BRAF-mutant NSCLC.Journal of Clinical Oncology, vol. 37, no. 15_suppl, American Society of Clinical Oncology (ASCO), 2019, pp. 3102–3102. Crossref, doi:10.1200/jco.2019.37.15_suppl.3102.
URI
https://scholars.duke.edu/individual/pub1415273
Source
crossref
Published In
Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology
Volume
37
Published Date
Start Page
3102
End Page
3102
DOI
10.1200/jco.2019.37.15_suppl.3102

Osimertinib for patients (pts) with leptomeningeal metastases (LM) associated with EGFRm advanced NSCLC: The AURA LM study.

Authors
Ahn, M-J; Chiu, C-H; Cheng, Y; Han, J-Y; Goldberg, SB; Greystoke, A; Crawford, J; Zhao, Y; Huang, X; Johnson, M; Vishwanathan, K; Mendoza-Naranjo, A; Mok, TSK
MLA Citation
Ahn, M. .. J., et al. “Osimertinib for patients (pts) with leptomeningeal metastases (LM) associated with EGFRm advanced NSCLC: The AURA LM study.Ann Oncol, vol. 30 Suppl 2, 2019, p. ii48. Pubmed, doi:10.1093/annonc/mdz063.003.
URI
https://scholars.duke.edu/individual/pub1370576
PMID
32131251
Source
pubmed
Published In
Ann Oncol
Volume
30 Suppl 2
Published Date
Start Page
ii48
DOI
10.1093/annonc/mdz063.003