Office of Clinical Research

Bethesda, MD, United States

Office of Clinical Research

Bethesda, MD, United States

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Pipas J.M.,Dartmouth Hitchcock Medical Center | Zaki B.I.,Dartmouth Hitchcock Medical Center | Mcgowan M.M.,Dartmouth Hitchcock Medical Center | Tsapakos M.J.,Dartmouth Hitchcock Medical Center | And 15 more authors.
Annals of Oncology | Year: 2012

Background: Neoadjuvant therapy has been investigated for localized and locally advanced pancreatic ductal adenocarcinoma (PDAC) but no standard of care exists. Combination cetuximab/gemcitabine/radiotherapy demonstrates encouraging preclinical activity in PDAC. We investigated cetuximab with twice-weekly gemcitabine and intensity-modulated radiotherapy (IMRT) as neoadjuvant therapy in patients with localized or locally advanced PDAC. Experimental design: Treatment consisted of cetuximab load at 400 mg/m.2 followed by cetuximab 250 mg/m.2 weekly and gemcitabine 50 mg/m.2 twice-weekly given concurrently with IMRT to 54 Gy. Following therapy, patients were considered for resection. Results: Thirty-seven patients were enrolled with 33 assessable for response. Ten patients (30%) manifested partial response and 20 (61%) manifested stable disease by RECIST. Twenty-five patients (76%) underwent resection, including 18/23 previously borderline and 3/6 previously unresectable tumors. Twenty-three (92%) of these had negative surgical margins. Pathology revealed that 24% of resected tumors had grade III/IV tumor kill, including two pathological complete responses (8%). Median survival was 24.3 months in resected patients. Outcome did not vary by epidermal growth factor receptor status. Conclusions: Neoadjuvant therapy with cetuximab/gemcitabine/IMRT is tolerable and active in PDAC. Margin-negative resection rates are high and some locally advanced tumors can be downstaged to allow for complete resection with encouraging survival. Pathological complete responses can occur. This combination warrants further investigation. © The Author 2012. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved.


News Article | February 21, 2017
Site: www.eurekalert.org

The National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health (NIH), has launched a Phase 1 clinical trial to test an investigational vaccine intended to provide broad protection against a range of mosquito-transmitted diseases, such as Zika, malaria, West Nile fever and dengue fever, and to hinder the ability of mosquitoes to transmit such infections. The study, which is being conducted at the NIH Clinical Center in Bethesda, Maryland, will examine the experimental vaccine's safety and ability to generate an immune response. The investigational vaccine, called AGS-v, was developed by the London-based pharmaceutical company SEEK, which has since formed a joint venture with hVIVO in London. The consulting group Halloran has provided regulatory advice to both companies. Unlike other vaccines targeting specific mosquito-borne diseases, the AGS-v candidate is designed to trigger an immune response to mosquito saliva rather than to a specific virus or parasite carried by mosquitoes. The test vaccine contains four synthetic proteins from mosquito salivary glands. The proteins are designed to induce antibodies in a vaccinated individual and to cause a modified allergic response that can prevent infection when a person is bitten by a disease-carrying mosquito. "Mosquitoes cause more human disease and death than any other animal," said NIAID Director Anthony S. Fauci, M.D. "A single vaccine capable of protecting against the scourge of mosquito-borne diseases is a novel concept that, if proven successful, would be a monumental public health advance." Led by Matthew J. Memoli, M.D., director of the Clinical Studies Unit in NIAID's Laboratory of Infectious Diseases, the clinical trial is expected to enroll up to 60 healthy adults ages 18 to 50 years. Participants will be randomly assigned to receive one of three vaccine regimens. The first group will receive two injections of the AGS-v vaccine, 21 days apart. The second group will receive two injections of AGS-v combined with an adjuvant, 21 days apart. The adjuvant is an oil and water mixture commonly added to vaccines to enhance immune responses. The third group will receive two placebo injections of sterile water 21 days apart. Neither the study investigators nor the participants will know who is assigned to each group. Participants will be asked to return to the clinic twice between vaccinations and twice after the second vaccination to undergo a physical exam and to provide blood samples. Study investigators will examine the blood samples to measure levels of antibodies triggered by vaccination. Each participant also will return to the Clinical Center approximately 21 days after completing the vaccination schedule to undergo a controlled exposure to biting mosquitoes. The mosquitoes will not be carrying viruses or parasites, so the participants are not at risk of becoming infected with a mosquito-borne disease. Five to 10 female Aedes aegypti mosquitoes from the insectary in NIAID's Laboratory of Malaria and Vector Research will be put in a feeding device that will be placed on each participant's arm for 20 minutes. The mosquitoes will bite the participants' arms through the netting on the feeding devices. Afterward, investigators will take blood samples from each participant at various time points to see if participants experience a modified response to the mosquito bites as a result of AGS-v vaccination. Investigators also will examine the mosquitoes after the feeding to assess any changes to their life cycle. Scientists suspect that the mosquitoes who take a blood meal from ASG-v-vaccinated participants may have altered behavior that could lead to early death or a reduced ability to reproduce. This would indicate that the experimental vaccine could also hinder disease transmission by controlling the mosquito population. All participants will be asked to return to the clinic for follow-up visits every 60 days for five months following the mosquito feeding. A final clinic visit to assess long-term safety will take place approximately 10 months after the mosquito feeding. Throughout the trial, an independent Data and Safety Monitoring Board will review study data to evaluate participant safety and the overall conduct of the study. A medical monitor from NIAID's Office of Clinical Research Policy and Regulatory Operations will also perform routine safety assessments. The study is expected to be completed by summer 2018. For more information about the trial, see ClinicalTrials.gov using the trial identifier NCT03055000. NIAID conducts and supports research--at NIH, throughout the United States, and worldwide--to study the causes of infectious and immune-mediated diseases, and to develop better means of preventing, diagnosing and treating these illnesses. News releases, fact sheets and other NIAID-related materials are available on the NIAID website. About the National Institutes of Health (NIH): NIH, the nation's medical research agency, includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. NIH is the primary federal agency conducting and supporting basic, clinical, and translational medical research, and is investigating the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit http://www. .


Staren E.D.,Office of Clinical Research | Gupta D.,Office of Clinical Research | Braun D.P.,Office of Clinical Research
Breast Journal | Year: 2011

While the use of quality of life (QoL) assessments has been increasing in oncology, few studies have examined the prognostic significance of QoL in breast cancer. We investigated the association between QoL at presentation and survival in breast cancer. We examined 1,511 breast cancer patients treated at two single-system cancer centers between January 2001 and December 2008. QoL was evaluated using the validated survey instrument EORTC-QLQ-C30. Patient survival was defined as the time interval between the date of first patient visit and the date of death from any cause/date of last contact. Univariate and multivariate Cox regression analyses were performed to evaluate the prognostic significance of QoL after controlling for the effects of age, tumor stage, and prior treatment history. Mean age at presentation was 52.5 years. There were 590 analytic and 921 non-analytic patients. Patient stage of disease at diagnosis was I, 335; II, 591; III, 290; IV, 159; and 136 indeterminate. Median overall survival was 32.8 months (95% CI: 27.6-38.0). On univariate analysis, QoL function and symptom scales that were predictive of survival were physical (p < 0.001), role (p < 0.001), cognitive (p = 0.003), social (p < 0.001), fatigue (p < 0.001), nausea/vomiting (p < 0.001), pain (p < 0.001), dyspnea (p < 0.001), loss of appetite (p < 0.001), and constipation (p < 0.001). On multivariate analyses, only role function (degree of impairment of work and/or leisure/hobby related activities) was significantly associated with survival. This study suggests that baseline QoL (in particular, the role function) provides useful prognostic information in breast cancer. © 2011 Wiley Periodicals, Inc.


Braun D.P.,Office of Clinical Research | Gupta D.,Office of Clinical Research | Staren E.D.,Office of Clinical Research
Pancreas | Year: 2013

Objective: We investigated whether changes in quality of life (QoL) during treatment could predict survival in stage IV pancreatic cancer. METHODS: Quality of life was evaluated at baseline and after 3 months of treatment using European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) in 186 patients with stage IV pancreatic cancer. Cox regression evaluated the prognostic significance of baseline and changes in QoL scores after adjusting for age, sex, and treatment history. RESULTS: One hundred twenty-one patients were males and 65 were females. One hundred twenty-seven patients' condition was newly diagnosed, whereas 59 were previously treated. The mean age at diagnosis was 55.1 years. Baseline QoL scale predictive of survival upon multivariate analysis was global health (hazard ratio, 0.88; 95% confidence interval, 0.81-0.95; P = 0.001). On multivariate analysis, QoL change variable that was significantly predictive of survival after 3 months of treatment was cognitive function (hazard ratio, 0.89; 95% confidence interval, 0.79-0.99; P = 0.04). CONCLUSIONS: This study provides preliminary evidence to indicate that patients with stage IV pancreatic cancer who have a better global health at baseline as well as those whose cognitive function improves within 3 months of treatment have a significantly increased probability of survival. Copyright © 2013 Lippincott Williams & Wilkins.


Braun D.P.,Office of Clinical Research | Gupta D.,Office of Clinical Research | Birdsall T.C.,Office of Clinical Research | Sumner M.,Office of Clinical Research | Staren E.D.,Office of Clinical Research
Journal of Alternative and Complementary Medicine | Year: 2013

Objectives: Use of naturopathic and nutritional supplements (NNS) with antioxidant activity is controversial in patients receiving radiation therapy. The effects of concomitant use of NNS with antioxidant activity during radiation therapy for prostate cancer were investigated in terms of clinical tumor responsiveness, kinetics, and durability. Materials and methods: A retrospective investigation was done of 134 patients treated with curative intent for limited-stage prostate cancer by radiation therapy. Patients self-selected to receive NNS as part of their treatment and maintenance during an extended post-treatment interval of at least 2 years. The outcome measures were the following: prostate-specific antigen (PSA) nadir; ≥24 months post-treatment PSA; time to reach nadir; and time to last follow-up were compared across +NNS and -NNS. Results: Sixty-nine (69) patients elected to receive NNS while 65 did not. Seventy-seven (77) (+NNS 39, -NNS 38) patients received hormone therapy while 57 (+NNS 30, -NNS 27) did not. In the nonhormone cohort, median pretreatment PSA, nadir, post-treatment PSA, time to reach nadir, and time to follow-up were 5.5 ng/mL, 0.56 ng/mL, 0.61 ng/mL, 25 months, and 39.7 months for the -NNS group and 5.1 ng/mL, 0.32 ng/mL, 0.44 ng/mL, 27 months, and 50.1 months for the +NNS group, respectively (p>0.05 for all). Similarly, no significant differences were observed between +NNS and -NNS in the hormone-receiving cohort. Conclusions: The clinical tumor response to radiation therapy in patients with limited-stage prostate cancer is not inhibited by concomitant NNS based on the magnitude of the PSA response, the velocity of the PSA nadir, and the duration of PSA normalization. © Copyright 2013, Mary Ann Liebert, Inc. 2013.


Gupta D.,Office of Clinical Research | Braun D.P.,Office of Clinical Research | Staren E.D.,Office of Clinical Research
European Journal of Cancer Care | Year: 2012

In patients with advanced cancer, quality of life is as meaningful to patients as the actual length of life. We investigated whether changes in quality of life could predict survival in non-small cell lung cancer. Quality of life was evaluated using EORTC QLQ-C30 (European Organisation for the Research and Treatment of Cancer Quality of Life Questionnaire). Cox regression evaluated the prognostic significance of baseline, 3-month and changes in quality of life scores after adjusting for age, gender, treatment history and stage. Two hundred and seventeen patients were men and 213 women. One hundred and fifty-nine patients had stage III while 271 had stage IV disease. Baseline quality of life scales predictive of survival upon multivariate analysis were physical (hazard ratio, 0.90; 95% confidence interval, 0.81-0.98; P= 0.02) and global (hazard ratio, 0.92; 95% confidence interval, 0.87-0.96; P < 0.001). On multivariate analysis, no change variables were significantly predictive of survival. However, in stage IV patients, change in physical function over a period of 3 months showed marginal significance such that every 10-point increase in physical function change score was associated with an 8% decreased risk of death. These findings should be used in clinical practice to systematically address quality of life-related problems of lung cancer patients throughout their treatment course. © 2012 Blackwell Publishing Ltd.


Braun D.P.,Office of Clinical Research | Gupta D.,Office of Clinical Research | Staren E.D.,Office of Clinical Research
Supportive Care in Cancer | Year: 2012

Purpose: While the use of quality of life (QoL) assessment has been increasing in clinical oncology, few studies have examined its prognostic significance in prostate cancer. We investigated the association between QoL at presentation and survival in prostate cancer. Methods: We retrospectively reviewed 673 patients treated at two single-system cancer centers between January 2001 and December 2008. QoL was evaluated using EORTCQLQ-C30. Patient survival was defined as the time interval between the date of first patient visit and the date of death/date of last contact. Univariate and multivariate Cox regression was performed to evaluate the prognostic significance of QoL. Results: Mean age at presentation was 63.2 years. Patient stage of disease at diagnosis was I, 4; II, 464; III, 76; IV, 107; and 22 indeterminate. Median overall survival was 89.1 months (95% CI: 46.1-132.0). QoL scales predictive of survival upon univariate analysis were physical, role, emotional, social, fatigue, nausea/vomiting, pain, dyspnea, insomnia, loss of appetite, and constipation (p<0.01 for all). Multivariate analyses found fatigue (p=0.02) and constipation (p=0.01) to be significantly associated with survival. Conclusions: Baseline QoL provides useful prognostic information in prostate cancer. These findings have important implications for patient stratification in clinical trials and may aid decision making in clinical practice. © The Author(s) 2011.


Wang Y.A.,University of California at Los Angeles | Wang Y.A.,Foundation Medicine | Feng A.-C.,Office of Clinical Research | Ganz P.A.,University of California at Los Angeles
Scientific Reports | Year: 2014

Surveillance guidelines for breast cancer survivors recommend regular history and physical and mammography, and against routine imaging for detecting distant metastasis. Stage 0, I, II breast cancer cases treated at a major cancer center were identified from the Taiwan Cancer Registry. We used multivariable negative binomial and logistic regression analyses on institutional claims data to examine factors contributing to utilisation patterns of surveillance visits and tests in disease-free survivors. The mean number of surveillance visits during months 13 to 60 after cancer treatment initiation was 18.5 (SD 8.2) among the 2,090 breast cancer survivors followed for at least five years. After adjusting for patient and disease factors, the number of visits was the highest among patients mainly followed by medical oncologists compared to surgeons and radiation oncologists. Patient cohorts treated in more recent years had lower number of visits associated with care coordination effort, the adjusted mean being 19.2 visits for the 2002 cohort, and 16.3 visits for the 2008 cohort (p < 0.0001). Although imaging tests were highly utilised, there was a significant decrease in tumor marker testing from the 2002 to the 2008 treatment cohort (adjusted rate 99.4% to 35.1% respectively, p < 0.0001) in association with an institutional guideline change.


Braun D.P.,Office of Clinical Research | Gupta D.,Office of Clinical Research | Grutsch J.F.,Office of Clinical Research | Staren E.D.,Office of Clinical Research
Health and Quality of Life Outcomes | Year: 2011

Background: Several studies have demonstrated the predictive significance on survival of baseline quality of life (QoL) in colorectal cancer (CRC) with little information on the impact of changes in QoL scores on prognosis in CRC. We investigated whether changes in QoL during treatment could predict survival in CRC.Methods: We evaluated 396 stages III-IV CRC patients available for a minimum follow-up of 3 months. QoL was evaluated at baseline and after 3 months of treatment using EORTC QLQ-C30. Cox regression evaluated the prognostic significance of baseline, 3-month and changes in QoL scores after adjusting for age, gender and stage at diagnosis.Results: After adjusting for covariates, every 10-point increase in both baseline appetite loss and global QoL score was associated with a 7% increased risk of death with HR = 1.07 (95% CI, 1.01-1.14; P = 0.02) and (HR = 0.93 (95% CI, 0.87-0.98; P = 0.01) respectively. A lower risk of death was associated with a 10-point improvement in physical function at 3 months (HR, 0.86; 95% CI, 0.78-0.94; P = 0.001). Surprisingly, a higher risk of death was associated with a 10-point improvement in social function at 3 months (HR, 1.08; 95% CI, 1.02-1.13; P = 0.008).Conclusions: This study provides preliminary evidence to indicate that CRC patients whose physical function improves within 3 months of treatment have a significantly increased probability of survival. These findings should be used in clinical practice to systematically address QoL-related problems of CRC patients throughout their treatment course. © 2011 Braun et al; licensee BioMed Central Ltd.


PubMed | Koo Foundation Sun Yat Sen Cancer Center and Office of Clinical Research
Type: Journal Article | Journal: PloS one | Year: 2016

Paravertebral block placement was the main anesthetic technique for modified radical mastectomy in our hospital until February 2014, when its combination with blocks targeting the pectoral musculature was initiated. We compared the analgesic effects of paravertebral blocks with or without blocks targeting the pectoral musculature for modified radical mastectomy.We retrospectively collected data from a single surgeon and anesthesiologist from June 1, 2012, to May 31, 2015. Intraoperative sedatives and analgesic requirements, time to the first analgesic request, postoperative analgesic doses, patient satisfaction, and complications were compared.Fifty-four patients received a paravertebral block alone (PECS 0), and 46 received a paravertebral block combined with blocks targeting the pectoral musculature (PECS 1). The highest intraoperative effect-site concentration of propofol was significantly lower in the PECS 1 group than in the PECS 0 group [2.3 (1.5, 2.8) vs 2.5 (1.5, 4) g/mL, p = 0.0014]. The intraoperative rescue analgesic dose was significantly lower in the PECS 1 group [0 (0, 25) vs 0 (0, 75) mg of ketamine, p = 0.0384]. Furthermore, the PECS 1 group had a significantly longer time to the first analgesic request [636.5 (15, 720) vs 182.5 (14, 720) min, p = 0.0001]. After further adjustment for age, body mass index, American Society of Anesthesiologists Physical Status classification, chronic pain history, incidence of a superficial cervical plexus block placement, and operation duration, blocks targeting the pectoral musculature were determined to be the only significant factor (hazard ratio, 0.36; 95% confidence interval, 0.23-0.58; p < 0.0001). Very few patients used potent analgesics including morphine and ketorolac; the cumulative use of morphine or ketorolac was similar in the study groups. However, the incidence of all analgesic use, namely morphine, ketorolac, acetaminophen, and celecoxib, was significantly lower in the PECS 1 group [3.5 (0, 6) vs 5 (0, 12), p < 0.0001].Compared with the placement of a paravertebral block alone, combining blocks targeting the pectoral musculature with a paravertebral block for modified radical mastectomy reduced the sedative and analgesic requirements during operation and provided more effective postoperative analgesia.

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