Ongoing Clinical Trials最新文献

{"title":"Abstract OT2-10-01: Treatment burden and capacity to manage care among patients with breast cancer","authors":"A. Cheng, M. Levy","doi":"10.1158/1538-7445.SABCS18-OT2-10-01","DOIUrl":"https://doi.org/10.1158/1538-7445.SABCS18-OT2-10-01","url":null,"abstract":"Patients with breast cancer spend significant time1, effort, and financial resources2 to combat the disease for years after their diagnosis. The large volume of healthcare tasks can cause patients to become overburdened, leading to reduced adherence with care plans and worse outcomes3. On the other hand, certain patient characteristics such as physical resilience, financial well-being, and supportive family environments increase patients9 capacity to manage care4. Assessing treatment burden and capacity when prescribing care has been applied to populations such as diabetes patients5. We are investigating this paradigm in treatment of patients with breast cancer. The goal of this preliminary study is to identify significant factors that contribute to treatment burden, capacity to manage care, and outcomes of overburden for patients with breast cancer. Through literature review, interviews with survivors, and expert panels of navigators and providers, we will develop a survey instrument given to patients at the time of diagnosis. The survey will assess patient capacity and help providers give treatment options based on attributes of the patient. Additionally, we will attempt to correlate survey results with treatment burden measures derived from electronic health record data at a population level1. With treatment personalized for patient capacity, patients should be better able to adhere to care plans leading to improved quality of life during treatment and beyond. Acknowledgements: The authors would like to thank Cheryl Jernigan, our patient advocate mentor, for her guidance in this project. We would also like to thank the Susan G. Komen Foundation for their support of this research. References: 1. Cheng, A. C. & Levy, M. A. Data Driven Approach to Burden of Treatment Measurement: A Study of Patients with Breast Cancer. AMIA Annu. Symp. proceedings. AMIA Symp.2016, 1756–1763 (2016). 2. Zafar, S. Y. et al. The financial toxicity of cancer treatment: a pilot study assessing out-of-pocket expenses and the insured cancer patient9s experience. Oncologist.18, 381–90 (2013). 3. Mair, F. S. & May, C. R. Thinking about the burden of treatment. BMJ.349, g6680–g6680 (2014). 4. Boehmer, K. R., Shippee, N. D., Beebe, T. J. & Montori, V. M. Pursuing Minimally Disruptive Medicine: Correlation of patient capacity with disruption from illness and healthcare-related demands. J. Clin. Epidemiol. (2016). 5. Ishii, H. et al. Reproducibility and Validity of a Questionnaire Measuring Treatment Burden on Patients with Type 2 Diabetes: Diabetic Treatment Burden Questionnaire (DTBQ). Diabetes Ther.9, 1001–1019 (2018). Citation Format: Cheng A, Levy M. Treatment burden and capacity to manage care among patients with breast cancer [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr OT2-10-01.","PeriodicalId":19476,"journal":{"name":"Ongoing Clinical Trials","volume":"6 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"74603975","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Abstract OT1-05-02: OPTIMA: A prospective randomized trial to validate the clinical utility and cost-effectiveness of gene expression test-directed chemotherapy decisions in high clinical risk early breast cancer","authors":"R. Stein, L. Hughes-Davies, A. Makris, I. Macpherson, C. Conefrey, L. Rooshenas, S. Pinder, J. Thomas, P. Hall, D. Cameron, H. Earl, B. Naume, C. Poole, D. Rea, S. Macintosh, V. Harmer, A. Morgan, C. Hulme, C. McCabe, N. Stallard, Helen B Higgins, J. Donovan, J. Bartlett, A. Marshall, J. Dunn","doi":"10.1158/1538-7445.SABCS18-OT1-05-02","DOIUrl":"https://doi.org/10.1158/1538-7445.SABCS18-OT1-05-02","url":null,"abstract":"Background:Multi-parameter tumour gene expression assays (MPAs) are widely used to estimate individual patient residual risk and to guide chemotherapy use in hormone-sensitive, HER2-negative early breast cancer. The TAILORx trial supports MPA use in a node-negative population. Evidence for MPA use in node-positive breast cancer is limited. OPTIMA (Optimal Personalised Treatment of early breast cancer usIng Multi-parameter Analysis) (ISRCTN42400492) aims to validate MPAs as predictors of chemotherapy sensitivity in a largely node-positive breast cancer population where prospective RCT (Randomised Controlled Trial) evidence is lacking. Methods: OPTIMA is a partially blinded multi-center RCT with an adaptive two-stage design. The main eligibility criteria are women and men age 40 or older with resected ER-positive, HER2-negative invasive breast cancer and up to 9 involved axillary lymph nodes. Randomisation is to standard management (chemotherapy and endocrine therapy) or to MPA-directed treatment using the Prosigna (PAM50) test. Those with a Prosigna tumour score (ROR_PT) >60 receive standard management whilst those with a low score (≤60) are treated with endocrine therapy alone. Endocrine therapy for pre-menopausal women includes ovarian suppression. The co-primary outcomes are (1) Invasive Disease Free Survival (IDFS) and (2) cost-effectiveness of test-directed treatment. Secondary outcomes include IDFS in patients with low-score tumours and quality of life. An integrated qualitative recruitment study addresses challenges to consent and recruitment and will build on experience from the feasibility study that a multidisciplinary approach at sites is important for recruitment success. Tumour blocks will be banked to allow evaluation of additional MPA technologies. Recruitment of 4500 patients over 5 years will permit demonstration of 3% non-inferiority of test-directed treatment, assuming 5-year IDFS of 85% with standard management, equivalent to a HR of 1.22. Inclusion of patients from the feasibility study will increase the power to test for non-inferiority. Results: The OPTIMA main trial opened in January 2017. Overall recruitment (including the feasibility study) will reach 1000 in August 2018. Recruitment in Norway will commence in July 2018. Characteristics of the OPTIMA main participants recruited to 31st May 2018 are shown in the table. Conclusion: OPTIMA is one of two large scale prospective trials validating the use of test-guided chemotherapy decisions in node-positive early breast cancer. It is expected to have a global impact on breast cancer treatment. Experience from the preliminary study and close engagement with centres will aid trial success. Funding: OPTIMA is funded by the UK NIHR HTA Programme (10/34/501). Views expressed are those of the authors and not those of the HTA Programme, NIHR, NHS or the DoH. Citation Format: Stein RC, Hughes-Davies L, Makris A, Macpherson IR, Conefrey C, Rooshenas L, Pinder SE, Thomas J, Hall PS, Ca","PeriodicalId":19476,"journal":{"name":"Ongoing Clinical Trials","volume":"21 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"73894206","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Abstract OT2-06-01: Highly innovative personalized RNA-immunotherapy for patients with triple negative breast cancer","authors":"M. Schmidt, S. Bolte, K. Frenzel, L. Heesen, E. Derhovanessian, V. Bukur, M. Diken, J. Gruetzner, S. Kreiter, A. Klein, A. Kuhn, D. Langer, M. Loewer, H. Lindman, A. Schneeweiss, O. Tuereci, U. Şahin","doi":"10.1158/1538-7445.SABCS18-OT2-06-01","DOIUrl":"https://doi.org/10.1158/1538-7445.SABCS18-OT2-06-01","url":null,"abstract":"Background: The treatment of triple negative breast cancer (TNBC) is hampered by the lack of established therapeutic targets such as hormone receptors or HER-2. Chemotherapy and radiotherapy is the standard of care, yet survival rates in TNBC remain poor. Approaches tailored to the patient9s individual tumor signature may lead to improved therapeutic outcome. We have set up a clinical workflow covering drug development (from target discovery to manufacturing) and drug release providing a custom-made investigational medicinal product (IMP) for each individual patient. Trial Design: A phase I/II trial assesses the feasibility, safety and biological efficacy of this personalized immunotherapy in three clinical sites in Germany and Sweden. TNBC patients (pT1cN0M0 – TxNxM0) after completion of initial standard of care therapy will be allocated to one of two study arms. Patients in ARM1 receive 8 vaccination cycles with a personalized combination of shared tumor-associated antigens, selected based on each patient tumor9s antigen-expression profile out of a WAREHOUSE of pre-manufactured mRNA vaccine. Patients in ARM2 receive the personalized mRNA WAREHOUSE vaccine followed by 8 vaccination cycles of an on-demand manufactured mRNA MUTANOME vaccine encoding up to twenty unique neo-epitopes of the individual patient identified by next generation sequencing. The mRNAs are administered intravenously as a nanoparticulate lipoplex formulation, which protects RNA from degradation, activates innate immunity, transfects APCs and consequently induces highly potent antigen-specific T-cell responses. The treatment of 12 patients in ARM1 is completed and enrolment of patients for ARM2 has started. Preliminary data show that the RNA-WAREHOUSE approach is feasible and can be applied safely. Biomarker analysis is ongoing. This approach is promising as it addresses the heterogeneity of TNBC. The TNBC-MERIT trial was initially funded by the EU Commission9s FP7 and led by BioNTech AG. Citation Format: Schmidt M, Bolte S, Frenzel K, Heesen L, Derhovanessian E, Bukur V, Diken M, Gruetzner J, Kreiter S, Klein A, Kuhn A, Langer D, Loewer M, Lindman H, Schneeweiss A, Tuereci O, Sahin U. Highly innovative personalized RNA-immunotherapy for patients with triple negative breast cancer [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr OT2-06-01.","PeriodicalId":19476,"journal":{"name":"Ongoing Clinical Trials","volume":"27 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"82844374","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Abstract OT1-11-01: The BRandO BiO registry – A multicenter regional registry for patients with primary breast and ovarian cancer with longitudinal biobanking and evaluation of epidemiological, life style and quality of life factors","authors":"J. Huober, G. Nagel, A. Rempen, E. Schlicht, F. Flock, S. Fritz, F. Thiel, L. Wiesmüller, R. Felderbaum, V. Heilmann, I. Bekes, V. Fink, S. Albrecht, N. Gregorio, M. Tzschaschel, K. Ernst, C. Wolf, P. Kuhn, T. Friedl, W. Janni, A. D. Gregorio","doi":"10.1158/1538-7445.SABCS18-OT1-11-01","DOIUrl":"https://doi.org/10.1158/1538-7445.SABCS18-OT1-11-01","url":null,"abstract":"Background: Further progress in the treatment of breast cancer will likely come from contributions of molecular biology and immunologic approaches. The search for druggable molecular aberrations may enable treatment based on the molecular profile. A better identification of patients with a high risk of relapse facilitates the selection of these pts for clinical trials investigating early therapeutic molecular-based interventions. Trial Design: The BRandO BiO Registry is a multi-center regional registry to record clinical, epidemiological, and biological data from patients with newly diagnosed breast and ovarian cancer at the University of Ulm, Dept. of Gynecology and 19 affiliated network hospitals and practices in the Alb-Allgau Bodensee region (outreach area of the Comprehensive Cancer Center Ulm). Longitudinal biobanking is included with collection of paraffin-embedded samples of the primary tumor as well as blood samples at first diagnosis, after 6 and 12 months and at first relapse to isolate and investigate cell-free and germline DNA. Epidemiological, life style and quality of life (QOL) questionnaires are collected at first diagnosis, after 12, 36 and 60 months. The follow up is planned for 10 years. Eligibility criteria: Patients with primary newly diagnosed untreated breast or ovarian cancer of ≥ 18 years are eligible; primary metastatic untreated disease is allowed. Exclusion criteria comprise severe neurological or psychiatric disorders interfering with the ability to give an informed consent, no consent for registration, storage and processing of the individual disease characteristics and bio samples, and any malignant tumor in the last 3 years (except in situ disease). Specific aims: To register the majority of patients with newly diagnosed breast or ovarian cancer in all BRandO-BiO participating centers of a well-defined geographical area. To assess clinical characteristics and outcome data (event-free survival, overall survival) of these patients. To evaluate the primary tumor of all patients for mutational (druggable) aberrations. Further to assess cell-free DNA in the serial blood samples at baseline, 6 and 12 months and correlate these results with clinical outcome data as well as tumor and patient characteristics to look for early markers predicting relapse. To perform a longitudinal assessment of the patients9 sociodemographic factors, comorbidities, lifestyle and QOL factors by analyzing serial questionnaires collected at recruitment and at 12, 36 and 60 months. Present accrual and target accrual: The BRandO BiO Registry started January 2016 in the Dept. of Gynecology, University of Ulm and February 2017 at the network hospitals and practices. Until June 2018, 1180 patients with primary breast or ovarian cancer have been enrolled. The current adherence to serial blood testing and serial questionnaires is good with a return rate of 90%. A sample size of 3000 patients is planned. Contact information: Jens Huober, University of ","PeriodicalId":19476,"journal":{"name":"Ongoing Clinical Trials","volume":"30 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"81382400","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Abstract OT3-06-02: An initial safety study of gedatolisib plus PTK7-ADC for metastatic triple-negative breast cancer","authors":"M. Radovich, Jeffrey P. Solzak, B. Hancock, A. Storniolo, B. Schneider, K. Miller","doi":"10.1158/1538-7445.SABCS18-OT3-06-02","DOIUrl":"https://doi.org/10.1158/1538-7445.SABCS18-OT3-06-02","url":null,"abstract":"Background: The PI3K pathway is dysregulated in the majority of triple-negative breast cancer (TNBCs). Contrary to the theory of oncogene addiction, single agent inhibition of the PI3K pathway in TNBC has had only modest activity. Our group has demonstrated preclinically that when PI3K is inhibited, an immediate compensatory up-regulation of the Wnt pathway occurs. The Wnt pathway is known known for its role in cancer metastases and can confer resistance to initial PI3K inhibition. Simultaneous dual targeting of both pathways is highly synergistic against TNBC models in vitro and in vivo. We have initiated a Phase I clinical trial using Gedatolisib (PI3K/mTOR inhibitor) and PTK7-ADC (Wnt pathway) for patients with metastatic TNBC (NCT03243331). Gedatolisib is a pan-class I isoform PI3K/mTOR inhibitor, and PTK7-ADC is an antibody-drug conjugate against the cell-surface PTK7 protein (Wnt pathway co-receptor) with an Auristatin payload. PTK7 is an attractive second target due to its up-regulation after PI3K inhibition and its known overexpression in TNBC. Further data has shown that the PTK7-payload, Auristatin, is in itself synergistic with Gedatolisib. The combination of using both of these drugs suggests a unique concept of “double synergy”. Where Gedatolisib increases the expression of the target of PTK7-ADC leading to one mechanism of synergy, and the Auristatin payload on PTK7-ADC is synergistic with Gedatolisib providing a second mechanism. Study Design: This is an open-label, Phase I, dose-escalation study with a 3 + 3 cohort design. The trial will enroll 12-18 patients. 3 cohorts of at least 3 patients will receive Gedatolisib (weekly) & PTK-ADC (q3w) at 110mg+1.4mg/kg, 180mg+1.4mg/kg, and 180mg+2.8mg/kg dose levels. Eligibility Criteria: This trial enrolls patients with metastatic triple negative (ER-, PgR-, HER2-) or low estrogen expressing (ER and PgR Objectives: The primary objective is to evaluate the safety of Gedatolisib plus PTK7-ADC. The secondary objective is to evaluate efficacy as determined by objective response rate, clinical benefit at 18 weeks, and progression free survival (PFS). Exploratory objectives will evaluate efficacy in patients with genomic aberrations in the PI3K pathway; and association of tumor DNA, RNA, plasma and circulating tumor cell sequencing with clinical efficacy to identify putative biomarkers. Correlative Sciences: We are collecting matched pre-/post-treatment tumor biopsies and serial blood samples to determine biomarkers of clinical response to inform subsequent trials. We plan to evaluate: 1) PI3K activity; 2) genomic aberrations in the PI3K pathway; 3) baseline PTK7 expression; 4) PTK7 upregulation after Gedatolisib treatment; and 5) mutations in plasma circulating tumor DNA. Supported by the BCRF, 100 Voices of Hope, Catherine Peachey Foundation, and Pfizer. Citation Format: Radovich M, Solzak JP, Hancock BA, Storniolo AMV, Schneider BP, Miller KD. An initial safety study of gedatolisib plus PTK7-","PeriodicalId":19476,"journal":{"name":"Ongoing Clinical Trials","volume":"29 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"83574117","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Abstract OT2-01-01: Not presented","authors":"B. Yang, Ju-fang Wu","doi":"10.1158/1538-7445.SABCS18-OT2-01-01","DOIUrl":"https://doi.org/10.1158/1538-7445.SABCS18-OT2-01-01","url":null,"abstract":"This abstract was not presented at the conference. Citation Format: Yang B, Wu J. Not presented [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr OT2-01-01.","PeriodicalId":19476,"journal":{"name":"Ongoing Clinical Trials","volume":"2014 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"88042443","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Abstract OT1-01-02: An open-label, randomized, multi-center phase 2 study evaluating the activity of lasofoxifene relative to fulvestrant for the treatment of postmenopausal women with locally advanced or metastatic ER+/HER2 - breast cancer (MBC) with an ESR1 mutation","authors":"P. Plourde, L. Schwartzberg, G. Greene, D. Portman, B. Komm, Sn Jenkins, P. Liu, Portman, M. Goetz","doi":"10.1158/1538-7445.SABCS18-OT1-01-02","DOIUrl":"https://doi.org/10.1158/1538-7445.SABCS18-OT1-01-02","url":null,"abstract":"Endocrine based therapy is the standard treatment for estrogen receptor positive (ER+) MBC. Agents targeting the ER pathway including aromatase inhibitors (AIs), fulvestrant and tamoxifen along with CDK 4/6 inhibitors are considered standard for first and 2nd line treatment. However, endocrine resistance develops in nearly all patients and the optimal systemic therapy after progression on a CDK 4/6 inhibitor is unknown. Lasofoxifene is a third generation SERM previously investigated for the treatment of osteoporosis and vulvo-vaginal atrophy (VVA). In a large phase 3 trial evaluating the efficacy of lasofoxifene for the postmenopausal treatment of osteoporosis, lasofoxifene significantly reduced the incidence of ER+ breast cancer. Further unpublished preclinical data have demonstrated significant in vitro and in vivo efficacy in non-clinical breast cancer models including models with and without ESR1 mutants. Moreover, lasofoxifene significantly reduced metastases in ESR1 mutated models. These non-clinical and clinical data provide a strong rationale to pursue a phase 2 clinical trial in women with ER+, ESR1 mutated MBC. This open-label, multi-center study will compare the efficacy and tolerability of lasofoxifene (5 mg orally daily) to fulvestrant (IM 500 mg D1,15,29 and then q30 D) in a 1:1 randomization. Inclusion criteria include postmenopausal women with ER+ advanced breast cancer; progression on a non-steroidal AI in combination with a CDK 4/6 inhibitor; and a known ESR1 mutation. Approximately 90 patients with measurable or evaluable disease (i.e. bone only) will be recruited to have at least 40 patients per treatment arm. The primary endpoint will be progression free survival (PFS) with secondary endpoints of objective response rate (ORR), clinical benefit rate (CBR), duration of response (DoR) and time to response (TTR). It is assumed that lasofoxifene will double the median PFS compared to fulvestrant in this ESR1 mutation patient population for a hazard ratio 0.5 and a power of 89% to reach a 1-sided p of The study will commence in 4Q2018 and will complete recruitment in 1 year. It is anticipated that 25-30 centers in the US will be participating. Citation Format: Plourde PV, Schwartzberg LS, Greene GL, Portman DJ, Komm BS, Jenkins SN, Liu P-Y, Portman MD, Goetz MP. An open-label, randomized, multi-center phase 2 study evaluating the activity of lasofoxifene relative to fulvestrant for the treatment of postmenopausal women with locally advanced or metastatic ER+/HER2 - breast cancer (MBC) with an ESR1 mutation [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr OT1-01-02.","PeriodicalId":19476,"journal":{"name":"Ongoing Clinical Trials","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"81992296","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Abstract OT2-09-01: Pilot study of denosumab inBRCA1/2mutation carriers scheduling for risk-reducing salpingo-oophorectomy","authors":"Trivedi, G. Samimi, J. Wright, K. Holcomb, J. Garber, N. Horowitz, N. Arber, E. Friedman, R. Wenham, Margaret House, H. Parnes, J. Lee, S. Abutaseh, L. Vornik, B. Heckman-Stoddard, P. Brown, K. Crew","doi":"10.1158/1538-7445.SABCS18-OT2-09-01","DOIUrl":"https://doi.org/10.1158/1538-7445.SABCS18-OT2-09-01","url":null,"abstract":"Background: Denosumab is a monoclonal antibody that inhibits RANKL and is approved for the prevention of fractures in patients with osteoporosis or bone metastases. The RANKL signaling pathway is also involved in BRCA1-associated mammary tumorigenesis via a progesterone-induced paracrine effect of RANKL on luminal progenitor cells. Pre-clinical studies have demonstrated that RANKL inhibition resulted in reduced proliferation of mammary tumors. Early findings from an ongoing pre-surgical study demonstrated that denosumab treatment resulted in decreased Ki67 proliferation index in benign breast tissue. Based on these data, denosumab is being pursued as a potential preventive agent for breast cancer in BRCA1 mutation carriers. While promising, the effect of RANKL inhibition on gynecologic tissues such as the ovaries and fallopian tubes, in which progesterone has a protective effect, is unknown. Trial design: We will conduct a multicenter, open-label randomized pilot study of presurgical administration of denosumab versus no treatment in premenopausal women with BRCA1/2 mutations undergoing risk-reducing salpingo-oophorectomy (RRSO). A total of 60 women will be randomized 1:1 to Arm 1) 3-4 doses of 120 mg denosumab subcutaneously every 4 weeks or Arm 2) No treatment. Participants will be stratified by 1) BRCA1 versus BRCA2 mutation status and 2) Use of hormonal contraceptives within the past 3 months (yes/no). Assuming a 10% unevaluable rate, we expect to have 54 evaluable participants (27 per arm). Eligibility criteria: 1) Premenopausal women (defined as 18 years; 2) Documented germline pathogenic mutation or likely pathogenic variant in the BRCA1 or BRCA2 gene; 3) Plan for RRSO with or without hysterectomy; 4) ECOG performance status ≤ 1 (Karnofsky ≥ 70%); 5) Normal organ and marrow function; 6) Negative pregnancy test and use of adequate contraception; 7) Willingness to take supplemental oral calcium and vitamin D3; 8) Dental examination within 6 months of enrollment and no evidence of active dental issues; 9) Ability to understand and willingness to provide informed consent. Specific aims: Our primary objective is to compare the effect of denosumab to no treatment on Ki67 expression in the fimbrial end of the fallopian tube. Secondary objectives are to assess Ki67 in ovary and endometrium; cleaved caspase-3, RANK/RANKL, ER/PR, CD44, and STAT3/pSTAT3 expression in fallopian tube, ovary, and endometrium; gene expression profiling in the fallopian tube and ovary; serum markers (progesterone, estradiol, C-terminal telopeptide) and denosumab levels; and toxicity. Statistical methods: The primary endpoint is post-treatment Ki67 expression in the fimbrial end of the fallopian tube in the denosumab arm compared to the no treatment arm. Assuming a standard deviation of 5.0%, we will have 82% power to detect a 4.0% absolute difference (or effect size of 0.8) in Ki67 proliferation index between the denosumab and no treatment groups by applying a 2-sample t-","PeriodicalId":19476,"journal":{"name":"Ongoing Clinical Trials","volume":"20 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"84329638","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Abstract OT3-02-06: Utilizing multiomic advanced diagnostics to identify CDK4/6 inhibitor response predictors and a post-treatment multiomic signature for patients with ER+/HER2- metastatic breast cancer (SIDEOUT-3)","authors":"M. Abu-Khalaf, M. Pierobon, N. Denduluri, F. Valdes-Albini, A. Forero-Torres, A. Clark, R. Yung, M. Mita, S. Christensen, K. Awerkamp, Bryant Dunetz, R. Murphy, C. Hatzis, D. Zelterman, L. Liotta, E. Petricoin","doi":"10.1158/1538-7445.SABCS18-OT3-02-06","DOIUrl":"https://doi.org/10.1158/1538-7445.SABCS18-OT3-02-06","url":null,"abstract":"Background: Palbociclib, ribociclib and abemaciclib are 3 cyclin-dependent kinase (CDK) 4/6 inhibitors (inh) approved by the FDA for treatment of patients (pts) with hormone receptor–positive (HR+) metastatic breast cancer (MBC). We hypothesize that measuring the signaling architecture of CDK 4/6 kinase signaling network will predict response to CDK 4/6 inh and identify pts who are unlikely to respond to CDK4/6 inh and can be treated with other FDA approved drugs or a clinical trial. Patients who develop disease progression on CDK 4/6 inh within 12 months of starting therapy are eligible for a unique mulit-omic based molecular analysis that can be used as a therapeutic decision support tool. Trial design: This is an open label, multicenter study prospectively evaluating the phosphoprotein-based CDK 4/6 kinase network within the tumors of 100 pts with HR + MBC who are candidates for standard 1st line treatment with a CDK 4/6 inh plus endocrine therapy (ET). Eligible pts must have pretreatment tissue from a metastatic lesion sufficient to complete baseline biomarker analysis using a novel Laser Capture Microdissecton (LCM) reverse phase protein array (RPPA) coupled approach to quantitatively analyze 8 specific proteins/phosphoproteins within the CDK 4/6 kinase signaling network (Total Rb; phospho Rb (S780); total Cyclin D1; phospho Cyclin D1 (S286); total p16INK; total p27KIP; phosphop27KIP (T187); phosphoFoxM1 (T600). Pts who develop disease progression within 12 months of starting CDK4/6 inh plus ET will be eligible for an optional biopsy of a soft tissue or bone metastatic lesion at time of disease progression for molecular analysis using a multi-omic CAP/CLIA laboratory assays to analyze post-therapy biopsies by RPPA, IHC analysis, RNA-Seq, and targeted exome sequencing. A molecular tumor board then provides the results to the treating physician as a therapeutic decision support tool outlining potential targets and possible therapies which may be used for further treatment. The primary objective is to demonstrate a correlation between one-year progression-free survival (PFS) and pre-treatment phospho RB levels. Secondary endpoints will examine the association between one-year PFS and 7 pre-specified CDK 4/6 signaling network markers. Thirteen of planned 100 patients have been enrolled. The study will be conducted at 12 centers. Clinical trial registry number 03195192 Citation Format: Abu-Khalaf MM, Pierobon M, Denduluri N, Valdes-Albini F, Forero-Torres A, Clark A, Yung R, Mita M, Christensen S, Awerkamp K, Dunetz B, Murphy R, Hatzis C, Zelterman D, Liotta L, Petricoin E. Utilizing multiomic advanced diagnostics to identify CDK4/6 inhibitor response predictors and a post-treatment multiomic signature for patients with ER+/HER2- metastatic breast cancer (SIDEOUT-3) [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr OT3-02-06.","PeriodicalId":19476,"journal":{"name":"Ongoing Clinical Trials","volume":"45 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89638128","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Abstract OT3-06-02: Expansion into multiple institutions for training in the use of the LUM Imaging System for intraoperative detection of residual cancer in the tumor bed of female subjects with breast cancer","authors":"Kate Smith, J. Ferrer, Barbara L. Smith, E. Hwang, K. Hunt, Daleela Dodge, S. Karp, S. Valente, I. Wapnir, L. Clark, D. Carr, P. Beitsch, D. Dyess, B. Lesnikoski, P. Blumencranz, N. Dekhne, L. Gold, A. Chagpar, K. Kacena, Livia Gjylameti, F. Geissler","doi":"10.1158/1538-7445.AM2018-CT166","DOIUrl":"https://doi.org/10.1158/1538-7445.AM2018-CT166","url":null,"abstract":"Background: Standard surgical techniques result in positive lumpectomy margins 20-40% of the time. These positive margins require surgical re-excision which places significant burden on the healthcare system and patients. The LUM Imaging System consists of a fluorescence-based imaging agent, a hand-held wide-field detector (LUM Imaging Device) used to image the surgical cavity walls intraoperatively in real-time after the resection of the main lumpectomy specimen, and a proprietary tumor detection algorithm that highlights regions in the tumor bed suspected to contain residual cancer. This imaging system was previously tested in a single-site clinical study. The current study is evaluating the imaging system in a multi-study, large patient cohort. Trial Design / Methods This trial (NCT03321929) is a non-randomized, open-label, multi-site trial designed to further refine the tumor detection algorithm utilized by the LUM Imaging System. This is a prospective, interventional feasibility study and is a pilot arm to a pivotal study which will evaluate the safety and efficacy of the LUM Imaging System. Up to 250 adult female breast cancer patients undergoing lumpectomies are being enrolled at sixteen medical centers across the US. LUM015, a fluorescence-based imaging agent, is injected prior to the subject’s lumpectomy procedure. Surgeons perform their standard of care lumpectomy followed by intraoperative imaging of the lumpectomy cavity with the LUM Imaging System. Specific Aims The primary objective is to assess performance characteristics of the LUM Imaging System and to refine the tumor detection algorithm. A secondary objective is to develop and refine the process of implementing the LUM Imaging System into institution-specific workflows during lumpectomies. Eligibility Criteria This study seeks to enroll women, over the age of 18 and with histologically or cytologically confirmed primary invasive breast cancer (IBC), ductal carcinoma in situ (DCIS) or a combination of IBC/DCIS undergoing a lumpectomy for their breast malignancy. In addition to be willing to follow study procedures, participating in an informed consent discussion, signing an informed consent form, and having baseline lab and screening values within protocol limits, enrolled subjects must meet the following key exclusion criteria: have no history of allergic reaction to polyethylene glycol, no history of allergic reaction to intravenous contrast agents, have not undergone any systemic therapies to treat their cancer, and will not be administered methylene blue or other dye for sentinel lymph node detection during their lumpectomy. Additional detailed eligibility criteria are listed in the protocol. Statistical Methods For categorical variables, summary tabulations of the number and percentage of patients within each category (with a category for missing data) of the parameter will be presented. For continuous variables, the number of patients, mean, median, standard deviation, min","PeriodicalId":19476,"journal":{"name":"Ongoing Clinical Trials","volume":"25 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2018-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"83372229","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}