Gary R. Morrow - US grants

This application proposes research development of a clinical psychologist with interests and expertise in the control of chemotherapy side effects using a biobehavioral approach. Anticipatory neusea and vomiting are significant side effects that develop in approximately 25% of patients receiving chemotherapy treatment for cancer. Converging lines of evidence from psychologic, pharmacologic and neurologic investigations suggest that anticipatory nausea/vomiting are learned or conditioned behaviors. Adequate control of chemotherapy side effects such as anticipatory nausea and vomiting is essential for maximizing cancer treatment effectiveness. Proposed research is directed toward optimizing currently available behavioral interventions for side effect control, developing a new technology for nausea assessment and an increased understanding of side effect etiology. To achieve these aims, the following career development activities designed to enhance systematic, integrated studies of side effect control are proposed: (1) randomized clinical trials to assess whether the biobehavioral treatment of systematic desensitization is as effective when done by oncologists and oncology nurses as it is when done by behavioral psychologists; (2) development and refinement of ambulatory physiologic monitoring for concomitants of patient-reported nausea; and (3) prospective studies on the etiology of anticipatory side effects to test the ability of an 8-question screening instrument given after a patient's first chemotherapy treatment to predict the development of anticipatory side effects. The research has anticipated long-term benefits in the improvement of patient compliance for both current treatment and randomized treatment research trials.

Anticipatory nausea and vomiting occurred in 25 percent of 568 consecutive chemotherapy outpatients previously studied for anticipatory side effects. Converging lines of evidence from psychologic, pharmacologic and neurologic investigations support the view that anticipatory nausea/vomiting is a learned or conditioned bahavior. Systematic Desensitization has been established experimentally as both a precise and effective treatment for maladaptive learned behaviors. A randomized clinical trial showed the antiemetic effectiveness of Systematic Desensitization when administered by an experienced behavioral psychologist for the control of anticiapatory nausea/vomiting (ANV). Research proposed in this continuation application systematically expands previous promising findings through two specific studies: The first investigates through a randomized comparative clinical trial, the degree to which Systematic Desensitization is effective when used by oncology clinical personnel for control of patients' ANV. The second tests the ability of a 7 question clinical profile to predict which chemotherapy patients will develop anticipatory side effects. Over 300 new patients a year enter chemotherapy research trials at the University of Rochester Cancer Research Center. All will be screened with the predictive clinical profile at their second treatment cycle. Anticipatory nausea/vomiting and other criteria for entry into the clinical trial will be assessed at the fourth cycle. A sample size of 90 patients randomized to two experimental and one control arm of the clinical trial will assure conventionally assumed levels of protection for type 1 (Alpha = .05) and type 2 (power = 0.80) experimental errors. The proposed study has the anticipated long-term benefit of improving patient compliance in both best current treatment (Phase IV) and randomized (Phase III) treatment research trials.

The University of Rochester Cancer Center (URCC), a research institute within the University of Rochester School of Medicine and Dentistry, proposes to continue serving as a Research Base for Community Clinical Oncology Program (CCOP) applicant institutions. A original Research Base serving the CCOP program since 1983, the URCC/CCOP Research Base has evolved and developed considerable resources for cancer control research activities. Nine CCOP clinical trials (five cancer treatment and four cancer control) have been developed, approved by NCI and implemented by affliates of our Research Base during the current grant renewal. Over fifty cancer control credits have been registered in each of the past two years. The URCC Research Base is committed to a process and climate that fosters protocol development through collaboration among member CCOPs and affliates, experienced cancer control experts at out Research Base, and consultants in cancer control areas. This competing renewal focuses on strengths in the development and implementation of cancer control studies as a University Cancer Center Research Base for cancer control only. We currently offer six NCI approved cancer control protocols: three are randomized intervention trials that examine the effectiveness of biobehavioral and pharmacologic interventions in reducing treatment related morbidity.

The University of Rochester Cancer Center (URCC), a research institute within the University of Rochester School of Medicine and Dentistry, proposes to continue serving as a Research Base for Community Clinical Oncology Program (CCOP) applicant institutions. An original Research Base serving the CCOP program since 1983, the URCC CCOP Research Base has evolved and developed considerable resources for cancer control research activities. This competing renewal focuses on strengths in the development and implementation of cancer control studies resulting from being a clinical cancer research base exclusively for cancer control research. The URCC Research Base is committed to a process and climate that fosters protocol development through collaboration among member CCOPs and affiliates, experienced cancer control experts at our Research Base, and consultants in cancer control areas. The beginning success of this is shown through the fact that over half (10 of 18) of our CCOPs and affiliates who have been with us for more than two years have proposed a concept that has been submitted to NCI. CCOP members and affiliates have proposed 14 cancer control concepts, five of which have been developed into protocols. Furthermore, six current or former protocols are chaired by CCOP members or affiliates. Over the past five years, 2573 patients (representing 876.0 credits) have been registered. The URCC Research Base has opened eight cancer control protocols and closed five cancer control protocols while serving a total of 21 regular and six minority based CCOP programs. There are currently 18 CCOPs accruing patients on five active cancer control protocols within the URCC network.

The University of Rochester Cancer Center (URCC), a research institute within the University of Rochester School of Medicine and Dentistry, proposes to continue serving as a Research Base for Community Clinical Oncology Program (CCOP) applicant institutions. An original Research Base serving the CCOP program since 1983, the URCC CCOP Research Base has evolved and developed considerable resources for cancer control research activities. This competing renewal focuses on strengths in the development and implementation of cancer control studies resulting from being a clinical cancer research base exclusively for cancer control research. The URCC Research Base is committed to a process and climate that fosters protocol development through collaboration among member CCOPs and affiliates, experienced cancer control experts at our Research Base, and consultants in cancer control areas. The beginning success of this is shown through the fact that over half (10 of 18) of our CCOPs and affiliates who have been with us for more than two years have proposed a concept that has been submitted to NCI. CCOP members and affiliates have proposed 14 cancer control concepts, five of which have been developed into protocols. Furthermore, six current or former protocols are chaired by CCOP members or affiliates. Over the past five years, 2573 patients (representing 876.0 credits) have been registered. The URCC Research Base has opened eight cancer control protocols and closed five cancer control protocols while serving a total of 21 regular and six minority based CCOP programs. There are currently 18 CCOPs accruing patients on five active cancer control protocols within the URCC network.

The University of Rochester Cancer Center (URCC), a research institute within the University of Rochester School of Medicine and Dentistry, proposes to continue serving as a Research Base for Community Clinical Oncology Program (CCOP) applicant institutions. An original Research Base serving the CCOP program since 1983, the URCC CCOP Research Base has evolved and developed considerable resources for cancer control research activities. This competing renewal focuses on strengths in the development and implementation of cancer control studies resulting from being a clinical cancer research base exclusively for cancer control research. A major focus of our efforts is on the reduction of treatment related morbidity to maximize the potential curative effect of cancer treatments. The URCC Research Base is committed to a process and climate that fosters protocol development through collaboration among member CCOPs and affiliates, experienced cancer control experts at our Research Base, and consultants in cancer control areas. The beginning success of this is shown through the fact that all but two of our 16 CCOP affiliates have proposed a concept that has been submitted to NCI. CCOP members and affiliates have proposed 18 cancer control concepts, five of which have been developed into protocols. Furthermore, six current or former protocols are chaired by CCOP members or affiliates.

[unreadable] DESCRIPTION (provided by applicant): The Cancer Control Research Training Curriculum (CCRTC) will provide MD and Ph.D. post doctoral trainees with the tools and experience to establish careers as outstanding independent investigators in cancer control and prevention research and to compete successfully for research funding. [unreadable] [unreadable] The CCRTC specialized core curriculum is a two year program organized around three broad areas of cancer control research where fifteen cancer control mentors from nine medical center departments share a common research focus and often collaborate on investigator-initiated, funded research in addition to their individual RO-1 grants. Each of three initial trainees (and two/yr, thereafter) will take required lectures, core courses, and seminars in research focus areas of: Patient-Oriented Research, Biostatistics and Informatics Research and Health Outcomes Research. Completion will lead to either a Master of Public Health degree with a specialization in Clinical Investigation or a Master of Science degree with a specialization in Medical Statistics. [unreadable] [unreadable] A coordinated Series of special seminars, workshops and other required didactic experiences such as mini-sabbaticals and networking opportunities will extend the training and education of each trainee and address their specific research and professional needs as determined by them, the Principal Investigator and the CCRTC Advisory Committee. Each trainee will be guided by two University of Rochester based mentors with expertise in Cancer Control as well as a third off-site mentor actively involved in NCI supported multicenter studies. By taking advantage of opportunities provided by the peer-reviewed funding of each mentor as well as the NCI-funded Community Clinical Oncology Program Research Base directed by the PI, trainees will have the opportunity to engage in transdisciplinary mentored research projects locally and/or in multiple institutions. [unreadable] [unreadable] Candidates will be recruited nationwide for the two-year program using an array of approaches to attract highly qualified scientists committed to careers in cancer control clinical investigation. A rigorous evaluation plan will closely track the performance of each trainee and assess the program's success in preparing its graduates for careers in cancer control intervention research. [unreadable] [unreadable] [unreadable]

DESCRIPTION (provided by applicant): The University of Rochester Cancer Center (URCC), a research institute within the University of Rochester School of Medicine and Dentistry, proposes to continue serving as a research base for Community Clinical Oncology Program (CCOP) applicant institutions. An original research base serving the CCOP program since 1983, the URCC has evolved and developed considerable resources for cancer control research activities. This competing renewal focuses on strengths in the development and implementation of cancer control studies resulting from being a clinical cancer center research base exclusively for cancer control research. The URCC CCOP Research Base is committed to a process and climate that fosters protocol development through collaboration among member CCOPs and affiliates, experienced cancer control experts at our research base and consultants in cancer control areas. The beginning success of this is shown through the fact that half (10 of 20) of our CCOPs who have been affiliated with us for more than seven years have proposed a concept that has been submitted to NCI. CCOP members and affiliates have proposed 16 cancer control concepts, six of which have been developed into protocols. Further, all but three of our currently active protocols are chaired or co-chaired by CCOP investigators. Over the past three years, 1762 participants (representing 972.9 credits) have been entered on URCC protocols. The URCC Research Base has opened seven cancer control protocols and closed two, and currently has a total of nine active cancer control protocols. The URCC and affiliated CCOPs have participated in five additional research projects funded outside the CCOP mechanism. During this renewal period, we added five new CCOPs for a total of 18 regular and two minority-based CCOPs within the URCC network.

[unreadable] DESCRIPTION (provided by applicant): Sleep disturbance, particularly insomnia, is far more prevalent in cancer survivors than in the general population. Insomnia is thought to occur in 40 percent to 65 percent of patients following anti-cancer treatment. Apart from its ubiquity, insomnia is strongly associated with fatigue and reduced quality of life (QOL) and is thought to be an important contributing factor to both. To date, very few studies have been conducted to determine if established methods used to treat insomnia in the general population, e.g., cognitive behavioral therapy for insomnia (CBT-I), are also effective in treating the insomnia that occurs with cancer and/or its treatment. New treatment strategies for this problem in cancer survivors are also needed, particularly ones that address the persistent fatigue that occurs in this patient group. A prime candidate for such research is modafinil. Preliminary data from our group show that modafinil reduces sleep problems and fatigue in breast cancer patients post treatment. We have also completed a study showing that modafinil enhances treatment compliance with CBT-I in patients with primary insomnia. These two initial studies, coupled with a recently published, very successful, randomized, controlled trial of CBT-I in breast cancer survivors, suggest a role for both CBT-I and modafinil in treating insomnia in cancer survivors. Accordingly, we propose that the combination of therapies will be particularly efficacious in cancer patients because the combined approach will allow for the management of the often interrelated symptoms of insomnia and fatigue in cancer survivors. Methods: 226 Breast cancer survivors with chronic insomnia will be recruited and randomized to one of four treatment conditions (CBT-I, modafinil, both, or neither). The seven-week intervention is designed to determine the efficacy and acceptability of these treatment strategies in reducing insomnia and fatigue and in improving QOL in cancer survivors. Assessments will be made by diary and by questionnaires before, during, two weeks following, and three months following the study intervention. In addition, pre- and post-intervention polysomnographic assessments will be conducted in 100 of the 226 patients in order to characterize the effects of these interventions on sleep architecture. [unreadable] [unreadable] [unreadable]

This is a revised competing renewal of the Cancer Control Research Training Curriculum (CCRTC) R25T from Dr. Gary Morrow of the University of Rochester. The two year training program provides MD and PhD trainees with the tools and experience to establish careers as outstanding independent investigators in cancer control and prevention research who can compete successfully for research funding. Trainees take required lectures, core courses, workshops and seminars in Patient-Oriented Research, Biostatistics and Informatics Research, and Health Outcomes Research to complete a Master of Public Health or a Master of Science degree with a specialization in Clinical Investigation, Medical Statistics or Translational Research. Through the peer-reviewed research of 18 potential mentors from 11 medical center departments, as well as the NCI-funded Community Clinical Oncology Program Research Base, trainees engage actively in transdisciplinary mentored research projects locally and in multiple institutions. Eighty-six applicants (41 males/45 females: 23 MD/63 PhD: 15 minority) were evaluated for our first five classes. Twenty-nine were invited for on-site interviews and 15 of the 20 offered, including 6 minority, accepted positions. Each of the 11 trainees who has participated in the program at least a year has obtained peer-reviewed, investigator-initiated funding, for a total to date of over $7,800,000. Six trainees have received Early Career Research awards from professional associations. Program trainees have submitted 132 separate manuscripts-84 have been published, 21 are in press with the rest under review.

DESCRIPTION (provided by applicant): A legacy Research Base serving the CCOP program since 1983, transitioning into NCORP, the University of Rochester (URCC) proposes to continue its research focus on decreasing physical and psychological treatment-related morbidity and mortality among cancer patients, survivors, and their care partners by improving the quality of cancer care that addresses toxicities and side effects stemming from the cancer experience. Over the past 30 years the URCC has evolved and developed considerable resources for cancer control and cancer care delivery research activities. The 4,871 credits earned during the last five-year renewal period by Research Base affiliates on URCC protocols are 22% of the total cancer control credits provided for the 14 research bases funded during that period, according to NCI CCOP Program Staff. Over the next five years, the Research Base will continue its commitment as a university-based NCORP Research Base, producing state-of-the-science cancer control and cancer care delivery research. Our process and organization fosters protocol development through close collaboration among community affiliates and experienced investigators; data collected through our clinical and observational trials informs future research and policy; we pioneer use of new methodologies and exploration of mechanistic pathways; and we are dedicated to increasing the diversity of participants in our trials and to training junior investigators and community affiliates. Fifty-seven different potential research concepts have been presented and discussed in open forum at the last five annual group meetings. Twenty-one of them were proposed by colleagues geographically outside the University including eight from community affiliates. Each of the current eight approved protocols is either chaired or co-chaired by current CCOP/MBCCOP community affiliates.

ABSTRACT This is a third competing renewal of the Clinical and Translational Cancer Control Research Training Program (CCRTP) R25T, transitioning into the T32 mechanism, led by Gary Morrow, PhD, MS, and Michelle Janelsins, PhD, MPH, of the University of Rochester (UR). The primary aim of the 2- to 3-year CCRTP is to provide MD and PhD trainees with the tools and experiences necessary to establish careers as outstanding independent investigators in cancer control research. This program fills an unmet need to train the next generation of cancer control investigators. As improvements in cancer treatments increase survival rates, there are 20 million cancer survivors and counting; these survivors continue to experience ongoing side effects that negatively impact quality of life. Thus, there is a greater need to better understand the numerous debilitating side effects of cancer treatment and develop interventions. The program combines didactic and ?hands-on? research training activities. Dr. Janelsins, a former graduate of the CCRTP, formally joined Dr. Morrow as MPI in 2018 to enhance the translational science component of the CCRTP, providing synergy with Dr. Morrow?s expertise in clinical trials. For example, a number of recent trainees have focused on biologic mechanisms of intervention effects to alleviate side effects, or understanding biologic, medical, and psychologic risk factors for those who may develop side effects. Dr. Morrow and Dr. Janelsins are joined by 21 multidisciplinary, outstanding, experienced R01- funded mentors and 3 junior mentors with NCI K Awards from 12 academic departments, and exceptional infrastructure support from the NCI-funded Community Oncology Research Program (NCORP) Research Base, the UR Clinical and Translational Sciences Institute (CTSI), among others, as well as unparalleled institutional support from which to draw upon expertise to conduct and publish independent analyses and develop their own independent clinical and translational research projects. These research experiences are complemented by completion of a Master of Science (MS or MPH) degree focused in clinical investigation, epidemiology, translational research, health services, or data science. For our last 5 classes, 82 applicants (50 males/32 females, 18 MD/63 PhD, 8 minority) have been evaluated; 27 were invited for on-site interviews and 15 of the 16 who were offered positions accepted, including 5 minority applicants. They have produced 145 unique manuscripts, obtained several outstanding research awards, and earned $4.1 million in research funding. To date, 29 of the 31 trainees who have completed the program (last 15 years) have obtained tenure-track academic positions, and achieved a total of $63 million in independent funding, including 25 R-grants. Throughout our history, we have recruited approximately 50% women and 30% minority trainees. A majority (94%) of our trainees are still in academic cancer research-focused careers at Assistant (15), Associate (11), and Full (3) Professor level; some have also become leaders or directors of major programs within cancer centers. Our next renewal will continue to build upon this momentum of success.

ABSTRACT: The University of Rochester Cancer Center (URCC) National Cancer Institute Community Oncology Research Program (NCORP) Research Base (RB) is a RB with 35+ years of experience conducting cancer control research (CCR) and cancer care delivery research (CCDR). The URCC NCORP RB?s vision is to help good people through lousy times when they experience cancer? by reducing cancer- and treatment- related morbidity stemming from toxicities and side effects. Since 2014, 35% (N=2,831) of all NCORP accrual credits resulted from enrollment of patients and survivors by our Community Affiliates on our 13 active URCC clinical trials. URCC and its Community Affiliates also enrolled 421 caregivers and more than 300 oncologists to our 13 active trials, as well as 1,752 patients and survivors to our 29 local pilot studies. URCC successfully enrolled and randomized over 30 individual community oncology practices to cluster randomized trials. Our investigators and staff submitted 8 new concepts/grants, with 18 new concepts/grants currently in development, and 29 active pilot studies. The significant and innovative contribution of URCC research to scientific knowledge and clinical care is evidenced by 1) 197 published manuscripts, 2) 209 presented abstracts, 3) 25 podium presentations at ASCO, 4) 82 outstanding research awards to our investigators, 5) 12 junior investigators successfully trained to conduct research in NCORP, and 6) 2,215 investigators, clinicians, and staff successfully trained to implement URCC NCORP RB protocols at community sites across the United States. Notable recognition of the significance of research conducted by the URCC RB and its investigators includes: 1) Best of JCO publication for 2017, 2) most cited article in JAMA Oncology for 2017, 3) one of the most significant advances in cancer research and care for 2018, 4) citation of our published research in virtually all existing supportive care treatment guidelines, and 5) leadership by 5 of our RB Executive Committee members in the development of 4 supportive care treatment guidelines. We accomplish our goal of reducing cancer- and treatment-related morbidity by working with cancer patients, survivors, and their caregivers from 592 community oncology practices across the United States to design and conduct CCR and CCDR, including translational and health equity outcomes, focused in symptom science. Our research develops and tests novel treatments for toxicities and side effects stemming from cancer and its treatments. We design and conduct phase I-III randomized clinical trials and longitudinal, prospective cohort studies. To meet its responsibilities as a RB and maintain its high level of productivity over the next funding period, the URCC RB will focus its resources and expertise on the following specific aims: Aim 1) to conduct CCR, Aim 2) to conduct CCDR, Aim 3) to conduct translational CCR, Aim 4) to conduct health equity CCR and CCDR, and Aim 5) to provide state-of-the-art training and mentoring for NCORP investigators and staff. With its proven track record of productivity and innovation, the URCC NCORP RB is expertly positioned to continue its pioneering symptom science research in the NCORP Network.