Ongoing Clinical Trials最新文献

{"title":"Abstract OT1-04-01: A phase IIB pre-surgical trial of oral tamoxifen (TAM) versus transdermal 4-hydroxytamoxifen (4-OHT) in women with DCIS of the breast","authors":"Kelly Benante, Yanfei Xu, M. B. Tull, A. J. Segura, Katrina M. Alber, Kiril Kalinichenko, Lifang Hou, B. Jovanovic, M. Perloff, B. Heckman-Stoddard, E. Dimond, S. Khan","doi":"10.1158/1538-7445.SABCS18-OT1-04-01","DOIUrl":"https://doi.org/10.1158/1538-7445.SABCS18-OT1-04-01","url":null,"abstract":"Background Ductal carcinoma in situ (DCIS) is diagnosed in 60,000 women annually in the US. TAM is proven to reduce risk of local recurrence and new primary breast cancer in women with estrogen receptor (ER) positive DCIS. However, acceptance of TAM has been low, primarily because of toxicity related to systemic exposure. Local delivery to the breast is an attractive alternative since low systemic levels could minimize toxicity. 4-OHT is an active metabolite of TAM. When formulated as a gel and applied to the breast skin, it is well tolerated, and results in 4-OHT breast tissue drug levels comparable oral TAM. In small pilot studies, its anti-proliferative effects on invasive breast tumors and DCIS are also similar to oral TAM [Lee O, et al. PMID 25028506]. The goal of our study is to validate these results in preparation for a Phase III trial of 4-OHT gel in comparison to oral TAM. Methods We are conducting a randomized, double-blinded, placebo-controlled, Phase IIB pre-surgical trial to demonstrate that daily application of 4-OHT gel will result in a reduction in the Ki-67 labeling index of DCIS lesions that is not inferior to that seen in women receiving daily oral TAM 20 mg daily. Ki-67 of the base-line diagnostic core needle biopsy will be compared to that of the therapeutic surgical excision sample after oral TAM or 4-OHT gel for 8 ± 2 weeks. Secondary endpoints include changes in Oncotype DCIS-Score, IHC markers (CD68, COX2, p16), hormone levels, coagulation markers, drug concentration in the plasma and breast tissue, the fraction of women with no residual DCIS in the surgical sample, and experienced symptoms. 100 women (assuming 20% non-evaluable samples or compliance issues) with DCIS (10% ER-positive) will be enrolled across six institutions into two intervention arms: oral TAM 20 mg daily, placebo gel and 4-OHT gel 4mg daily (2mg/breast), placebo capsule. All participants will be evaluable for toxicity from their first dose. All samples from all participants who receive drug will be evaluated and included in the primary analysis, which will be based on intent to treat principle. To date 15 of 100 participants have been enrolled across six institutions including: Northwestern University in Chicago, IL, St. Elizabeth Healthcare in Edgewood, KY, Duke University Medical Center in Durham, NC, Cleveland Clinic in Cleveland, OH, Memorial Sloan Kettering Cancer Center in New York, NY, and Mayo Clinic in Rochester, MN. Since study open, 69 potential participants have been contacted, 52 did not consent for screening, 17consented for screening, 2 are pending consent, and 15 have started study intervention. The most common reasons potential participants chose not to consent are wanting to schedule surgery as soon as possible, attitudes toward medical research, and current use of a prohibited concomitant medication such as a potent inhibitor of tamoxifen metabolism or exogenous sex steroid. Funding Source: NCI Contract # HHSN2612201200035I. Citatio","PeriodicalId":19476,"journal":{"name":"Ongoing Clinical Trials","volume":"57 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"81403444","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 OT3-02-02: PATHWAY: Asian, multicenter, phase 3 trial of tamoxifen with or without palbociclib ± goserelin in women with hormone receptor-positive, HER2-negative advanced or metastatic breast cancer","authors":"E. Noguchi, T. Hata, Kenichi Nakamura, A. Kuchiba, M. Hayashi, A. Hamada, K. Yonemori, J. Sohn, Y. Lu, Y. Yap, Y. Fujiwara, K. Tamura","doi":"10.1158/1538-7445.sabcs18-ot3-02-02","DOIUrl":"https://doi.org/10.1158/1538-7445.sabcs18-ot3-02-02","url":null,"abstract":"BACKGROUND: The incidence rates of breast cancer (BC) in Asian counties have been rising rapidly. The age-specific female BC incidence rates peak before menopause (around 40-50 years of age) in Asia, however treatment options for pre/perimenopausal patients are limited. Palbociclib (P) is an oral novel cyclin-dependent kinase 4/6 (CDK4/6) inhibitor. The addition of P to endocrine therapy (ET) such as aromatase inhibitor or fulvestrant has been demonstrated improved progression-free survival (PFS) in phase 3 studies PALOMA-2 and PALOMA-3. This study is designed to evaluate efficacy and safety of P plus tamoxifen (TAM) in patients with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced or metastatic BC regardless of menopausal status. This study is conducted as a Clinical Research Collaboration by National Cancer Center Hospital with research funding from Pfizer. TRIAL DESIGN: PATHWAY/NCCH1607 is a double-blind, placebo-controlled, randomized, phase 3 study. Patients will be randomized 1:1 to receive either P (125 mg once daily, days1-21 of a 28-day cycle) or placebo in combination with TAM (20 mg once daily, continuously). Pre/perimenopausal women should receive concurrent ovarian function suppression with goserelin. Randomization will be stratified by prior ET for advanced/metastatic BC (1st line ET vs. 2nd line ET) and menopausal status (pre/perimenopausal vs. postmenopausal). KEY ELIGIBILITY CRITERIA: Eligible patients include women of any menopausal status with HR-positive, HER2-negative advanced or metastatic BC; candidates to receive TAM as 1st line or 2nd line ET for advanced/metastatic disease; ≥18 years of age; measurable or non-measurable disease (RECIST v.1.1); ECOG performance status 0-1; adequate organ function; have not received treatment with TAM (except for patients who have had more than 12 months from completion of adjuvant therapy with TAM); and have not received any CDK4/6 or phosphoinositide 3-kinase (PI3K) - mammalian target of rapamycin (mTOR) inhibitors. SPECIFIC AIMS: The primary endpoint is PFS as assessed by the investigator. Secondary endpoints include overall survival (OS), 1, 2, and 3-year survival probabilities, objective response (OR), duration of response, clinical benefit rate (CBR), pharmacokinetics, safety, and patient-reported outcomes. STATISTICAL METHODS: The sample size was determined to detect a 38% reduction in the hazard of disease progression or death in P plus TAM arm with a 1-sided significance level of 2.5% and power of 80%. A stratified log rank test will be used to compare PFS between the 2 treatment arms. PRESENT ACCRUAL AND TARGET ACCRUAL: Target accrual of 180 patients will be enrolled within 23 sites among Japan, Korea, Taiwan, and Singapore. As of June 2018, 46 patients have been enrolled. CONTACT INFORMATION: This trial is registered at ClinicalTrials.gov NCT03423199 and UMIN000030816. For more information, email NCCH1607_office@ml.res.ncc.go.jp C","PeriodicalId":19476,"journal":{"name":"Ongoing Clinical Trials","volume":"10 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"83562505","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 OT1-10-01: DETECT III/IV study trial – The multicenter study program in patients with HER2-negative metastatic breast cancer and circulating tumor cells","authors":"Sabrina Krause, T. Friedl, T. Romashova, P. Fasching, A. Schneeweiss, V. Müller, F. Taran, P. Arkadius, T. Marie, A. D. Gregorio, F. Meier-Stiegen, J. Huober, W. Janni, T. Fehm","doi":"10.1158/1538-7445.SABCS18-OT1-10-01","DOIUrl":"https://doi.org/10.1158/1538-7445.SABCS18-OT1-10-01","url":null,"abstract":"","PeriodicalId":19476,"journal":{"name":"Ongoing Clinical Trials","volume":"26 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"86474473","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 OT1-12-01: Exploration of factors associated with imminent risk of late recurrence in hormone receptor positive breast cancer","authors":"K. Jerzak, D. Cescon, S. Chia, S. Bratman, M. Ennis, V. Stambolic, Martin C. Chang, R. Dowling, P. Goodwin","doi":"10.1158/1538-7445.sabcs18-ot1-12-01","DOIUrl":"https://doi.org/10.1158/1538-7445.sabcs18-ot1-12-01","url":null,"abstract":"","PeriodicalId":19476,"journal":{"name":"Ongoing Clinical Trials","volume":"363 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"76587747","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 OT2-07-02: Trastuzumab deruxtecan (DS-8201a) vs investigator's choice of treatment in subjects with HER2-positive, unresectable and/or metastatic breast cancer who previously received T-DM1: A randomized, phase 3 study","authors":"F. André, J. Shahidi, C. Lee, K. Wang, I. Krop","doi":"10.1158/1538-7445.SABCS18-OT2-07-02","DOIUrl":"https://doi.org/10.1158/1538-7445.SABCS18-OT2-07-02","url":null,"abstract":"Background: There is no uniform standard of care for HER2-positive breast cancer (BC) after disease progression on ado-trastuzumab emtansine (T-DM1). DS-8201a is a novel HER2-targeted antibody-drug conjugate (ADC) with a humanized HER2 antibody attached to a topoisomerase I inhibitor payload by a cleavable peptide-based linker, and with a drug-to-antibody ratio of 7 to 8. It is designed with the goal of improving critical attributes of an ADC. In an ongoing phase 1 trial, DS-8201a showed promising antitumor activity in HER2-positive BC previously treated with T-DM1 (confirmed objective response rate [ORR] of 54.5%; April 2018 data cutoff; Iwata et al, ASCO 2018). Based on preliminary results from the phase 1 trial, DS-8201a received FDA breakthrough therapy and fast track designations for metastatic BC that progressed after prior treatment with T-DM1. The pivotal, phase 2 DESTINY-BREAST01 trial in this population with HER2-positive BC who received prior T-DM1 is ongoing (Baselga et al, ASCO 2018). Study Description: This multicenter, open-label, phase 3 trial will assess the efficacy and safety of DS-8201a in subjects with HER2-positive (IHC 3+ or IHC 2+/ISH+; confirmed by centralized testing) unresectable and/or metastatic BC whose disease progressed on or after T-DM1 (NCT03523585, DESTINY-BREAST02). Approximately 600 subjects will be randomized (2:1) to DS-8201a or investigator9s choice of treatment (trastuzumab plus capecitabine or lapatinib plus capecitabine). Randomization is stratified by hormone receptor status, prior pertuzumab treatment, and history of visceral disease. DS-8201a (5.4 mg/kg) will be administered IV once every 3 weeks. Progression free survival (PFS) based on blinded, independent central review using RECIST v1.1 criteria is primary efficacy endpoint; overall survival (OS) is the key secondary endpoint. Other secondary efficacy endpoints are ORR, duration of response, clinical benefit rate, and PFS based on investigator assessment. Safety assessments include serious and treatment-emergent adverse events, physical examinations, vital signs, and clinical laboratory parameters. Health-related quality of life will also be measured. The primary analysis for PFS will occur when approximately 372 PFS events have been observed; providing 90% power to detect a hazard ratio of 0.70 in PFS (a 43% improvement in median PFS from 3.3 months with investigator9s choice to 4.7 months with DS-8201a) with a 1-sided alpha of 0.025. An interim OS analysis is planned at the time of the PFS analysis. Final OS analysis will occur when approximately 428 OS events have been observed. Long-term follow-up will continue after the primary analysis every 3 months until death, withdrawal of consent, loss to follow-up, or study closure. Efficacy analyses will include all randomized subjects, and safety analyses will include all randomized subjects who received ≥1 dose of study treatment. The study will enroll subjects from approximately 160 sites including","PeriodicalId":19476,"journal":{"name":"Ongoing Clinical Trials","volume":"37 2 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"75730651","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 OT3-05-03: MEDIOLA: An open-label, phase I/II basket study of olaparib (PARP inhibitor) and durvalumab (anti-PD-L1 antibody)–Additional breast cancer cohorts","authors":"S. Domchek, S. Postel-Vinay, S. Im, Y. Park, J. Delord, A. Italiano, J. Alexandre, B. You, S. Bastian, M. Krebs, S. Waqar, M. Lanasa, H. Angell, M. Tang, C. Gresty, L. Opincar, P. Herbolsheimer, B. Kaufman","doi":"10.1158/1538-7445.SABCS18-OT3-05-03","DOIUrl":"https://doi.org/10.1158/1538-7445.SABCS18-OT3-05-03","url":null,"abstract":"Background: Olaparib (Lynparza®) is a PARP inhibitor that alters the repair of single-strand DNA breaks. Durvalumab (Imfinzi®) is a monoclonal antibody against programmed cell death ligand 1 (anti-PD-L1) that promotes antitumor immune responses. MEDIOLA (NCT02734004) is a Ph I/II open-label, multicenter study enrolling patients (pts) across several tumor types (small-cell lung cancer, gastric cancer, germline BRCA-mutated [gBRCAm] BC, or platinum sensitive relapsed gBRCAm ovarian cancer). 34 pts with gBRCAm BC received olaparib 300 mg po bid for a 4-wk run-in, followed by olaparib 300 mg po bid and durvalumab 1.5 g IV q4 wks. Encouraging preliminary results support an expansion cohort in a BRCAm popn. Evidence suggests that mutations in other homologous recombination repair (HRR) genes may confer a BRCA-like phenotype, warranting an expansion of the study population beyond BRCAm. Inhibition of vascular endothelial growth factor (VEGF) has been reported to enhance the efficacy of chemotherapy in TNBC. In addition, VEGF inhibition potentiates PARP inhibitor activity, particularly in pts who do not carry BRCAm. Combinations of immune checkpoint inhibitors and bevacizumab, an anti-VEGF-A antibody, have shown promising results in other tumor types. Thus, MEDIOLA will additionally explore the efficacy and safety of olaparib + durvalumab in combination with bevacizumab in TNBC pts. Trial design: Pts in the additional MBC cohorts will receive combination olaparib and durvalumab with no olaparib run-in. Pts in the TNBC cohort will also receive concurrent bevacizumab 10 mg/kg q 2 wks. Tumor assessments will be performed at baseline and every 8 wks thereafter. Eligibility criteria: Pts with histologically confirmed, locally advanced or metastatic HER2-neg BC, who are PARP-inhibitor and immunotherapy naive. Prior anthracycline and/or taxane therapy in early or MBC is required. Prior platinum therapy is allowed, if there was no disease progression while receiving treatment and at least 12 mths has elapsed since the last dose. Pts will undergo BRCA and HRR mutation testing and will be assigned to a cohort based on their mutation status, as illustrated in Table 1. Specific aims: Cohort-specific primary efficacy endpoint targets were calculated aiming for superiority to standard of care treatment (Table 1). Other primary outcomes are safety and tolerability. Secondary endpoints are PK, DCR at 24 wks, objective response rate, duration of response, progression-free survival and overall survival. Exploratory endpoints include the analysis of tumor-infiltrating lymphocytes and PD-L1 expression. Statistical methods: The expansion cohort will have a single-stage statistical design. Bayesian predictive probability design will be used for the analysis of the HRRm and TNBC triplet cohorts. Accrual: Accrual targets are shown in Table 1. First subject will be enrolled in Nov 2018. Citation Format: Domchek SM, Postel-Vinay S, Im S-A, Hee Park Y, Delord J-P, Italiano A, Alex","PeriodicalId":19476,"journal":{"name":"Ongoing Clinical Trials","volume":"PP 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"84161154","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 OT2-04-03: Examining personalized radiation therapy (EXPERT): A randomised phase III trial of adjuvant radiotherapy vs observation in patients with molecularly characterized luminal A breast cancer","authors":"B. Chua, K. Gray, M. Krishnasamy, M. Regan, N. Zdenkowski, S. Loi, B. Mann, J. Forbes, N. Wilcken, A. Spillane, A. Martín, H. Badger, S. Jafari, A. Fong, C. Mavin, S. Corachan, A. Arahmani, J-L Martinez, P. Francis","doi":"10.1158/1538-7445.SABCS18-OT2-04-03","DOIUrl":"https://doi.org/10.1158/1538-7445.SABCS18-OT2-04-03","url":null,"abstract":"","PeriodicalId":19476,"journal":{"name":"Ongoing Clinical Trials","volume":"22 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"85713486","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 OT2-06-05: A randomized phase II study of peri-operative ipilimumab, nivolumab and cryoablation versus standard peri-operative care in women with residual triple negative early stage/resectable breast cancer after standard-of-care neoadjuvant chemotherapy","authors":"H. McArthur, E. Comen, S. Solomon, M. Rodine, C. Abaya, J. Leal, S. Patil, L. Norton","doi":"10.1158/1538-7445.SABCS18-OT2-06-05","DOIUrl":"https://doi.org/10.1158/1538-7445.SABCS18-OT2-06-05","url":null,"abstract":"Background: Triple negative breast cancer (TNBC) is a biologically distinct subtype with high risk of early relapse, particularly for patients who do not achieve a pathological complete response (pCR) after neoadjuvant chemotherapy (NAC), with an event free survival of Methods: Eligible pts are aged ≥18 years, with ER, PR and HER2 negative operable tumors ≥ 1.0 cm after neoadjuvant taxane-based chemotherapy. Approximately 160 patients will be randomized to one of two arms: standard-of-care breast surgery (control arm) or ipi/nivo/cryo followed by standard-of-care breast surgery (intervention arm). Subjects randomized to the intervention arm will undergo percutaneous, ultrasound- (or MRI-) guided cryoablation with concurrent research core biopsy 7-10 days prior to surgery, and will receive a pre-operative infusion with ipilimumab at the dose of 1mg/kg IV, and nivolumab 240mg flat dose IV (1 to 5 days prior to cryoablation). After surgery, patients will receive three additional doses of nivolumab 240mg flat dose IV Q2 weeks. Adjuvant capecitabine is recommended for all participants and will be administered per standard-of-care at the treating physician9s discretion. Patients will be stratified by prior platinum administration, prior anthracycline administration, and clinical nodal status (positive versus negative) at enrollment. The primary endpoint is 3-year Event Free Survival (EFS). Secondary end points include Invasive Disease-Free Survival (IDFS), Distant Disease-Free Survival (DDFS), overall survival (OS) and safety. Exploratory correlative studies will be performed on tumor and serum to characterize the immunologic impact of the intervention and to explore predictors of efficacy and toxicity. Citation Format: McArthur HL, Comen EA, Solomon S, Rodine M, DiLauro Abaya C, Leal JHS, Patil S, Norton L. A randomized phase II study of peri-operative ipilimumab, nivolumab and cryoablation versus standard peri-operative care in women with residual triple negative early stage/resectable breast cancer after standard-of-care neoadjuvant chemotherapy [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 OT2-06-05.","PeriodicalId":19476,"journal":{"name":"Ongoing Clinical Trials","volume":"14 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"81819253","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 OT1-08-01: A pilot randomized usual care controlled study of yoga for persistent chemotherapy-induced peripheral neuropathy (CIPN) in breast and gynecological cancer survivors","authors":"W. Zhi, Mc Leeolou, L. Piulson, Phang-lang Chen, C. Patterson, T. Paul, S. Patil, J. Mao, T. Bao","doi":"10.1158/1538-7445.SABCS18-OT1-08-01","DOIUrl":"https://doi.org/10.1158/1538-7445.SABCS18-OT1-08-01","url":null,"abstract":"Background: CIPN is a common, painful, and debilitating side effect of many standard chemotherapy regimens. Patients with CIPN typically experience paresthesia (tingling, numbness), pain, and muscle weakness, and may exhibit significant functional decline and diminished quality of life. Our prior study showed that more than half of breast cancer survivors experience persistent CIPN up to a mean duration of 5.6 years and that this symptom is associated with a doubled fall risk. There is an urgent need to identify nonpharmacological approaches to reduce CIPN symptoms and improve cancer survivors9 functional outcomes. Yoga is a mind-body modality that includes stretching, flexibility, and balance training; however, little is known about its effects on symptoms and functional outcomes among cancer survivors with CIPN. Trial Design: We are conducting a two-arm pilot randomized usual care controlled trial in breast and gynecological cancer survivors at Memorial Sloan Kettering Cancer Center (MSK), New York, NY. Eligible subjects in the intervention arm receive one-hour Hatha Yoga classes taught twice weekly for eight weeks, and practice home-based yoga for a total of 12 weeks. Subjects in the wait list control (WLC) arm continue usual care for 12 weeks, followed by eight weeks of yoga classes and home-based yoga. Eligibility Criteria: 1) Patients with a primary diagnosis of stage I-III breast, ovarian, uterine, or endometrial cancer; 2) moderate to severe CIPN, defined by four or greater on a 0–10 Numeric Rating Scale (NRS); 3) completion of neurotoxic chemotherapy at least three months prior; 4) no changes in anti-neuropathy medications within three months of enrollment; and 5) an ECOG performance status of 0–2. Specific Aims: The primary endpoint is safety, feasibility, and NRS changes at eight weeks (end of treatment). The secondary endpoints include the Neuropathic Pain Scale (NPS) and Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity (FACT/GOG-Ntx) at eight, 12, and 20 weeks. Statistical Methods: We will accrue 40 patients to get 36 patients evaluable for the primary endpoint at eight weeks. Using an ANCOVA analysis with a sample size of 36, we will be able to detect an effect size of 00.58 standard deviations (SD) of NRS (moderate effect size) between yoga and WLC assuming a NRS correlation between pre- and post-yoga of 0.5 SD. If we assume a 10% dropout rate based on our recently completed trial, we will need to recruit 20 subjects per arm (total of 40) to fall within the precision noted in the sample size calculation. We recognize that the sample size calculation was based on detecting a moderate effect between yoga and WLC and may miss small but clinically meaningful effects that can be used to design a future trial that is sufficiently powered. Present accrual and target accrual: 40 participants. We have accrued 25 participants as of June 2018 and anticipate accrual completion by October 2018. Citation Format: Z","PeriodicalId":19476,"journal":{"name":"Ongoing Clinical Trials","volume":"319 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"80186187","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 OT1-12-04: A phase IIIb, open-label, local, multicenter study of the molecular features of postmenopausal women with hormone receptor-positive (HR+) HER2-negative advanced breast cancer on first-line treatment with ribociclib and letrozole (BioItaLEE)","authors":"M. Laurentiis, G. Arpino, G. Bianchini, L. Malorni, D. Castelletti, R. Vecchi, D. Grasso","doi":"10.1158/1538-7445.SABCS18-OT1-12-04","DOIUrl":"https://doi.org/10.1158/1538-7445.SABCS18-OT1-12-04","url":null,"abstract":"Background: characterizing the molecular features associated with prolonged benefit from CDK 4/6 inhibitors in HR+ HER2- BC and the acquired genomic alterations following treatment progression remains an unmet need and is crucial for leveraging the efficacy of CDK4/6 inhibitors and for elucidating resistance mechanisms. Identifying pre-treatment or pharmacodynamic predictive markers of treatment benefit, as well as predictive markers of toxicity by correlating pharmacogenomics with adverse events, could help physicians to select patients who may benefit the most from these therapies and improve the clinical management. Trial design: this is an Italian, multicenter, open-label, single-arm trial (NCT03439046) enrolling approximately 350 HR+ HER2- aBC first line patients in 48 sites. Patients are treated with ribociclib and letrozole and eligibility criteria are similar to the MONALEESA-2 trial. Patients will be followed for safety and efficacy outcomes. An extensive prospective collection of biological samples at different time points will be performed as follow: whole blood and plasma at baseline, cycle 1-D15, cycle 2-D1, at first imaging evaluation, at cycle 24-D1, as well as upon progression of disease; newly obtained tissue biopsies at baseline and at progression; a buccal swab for pharmacogenetics at baseline. Efficacy and safety data will be collected for all patients. Aims: the primary objective of this study is to identify circulating tumor DNA (ctDNA) alterations at baseline, to describe their evolution during treatment and to evaluate the association with clinical outcome. An optimized Next Generation Sequencing approach for the detection of low abundance events in ctDNA will be adopted. Single nucleotide variants and copy number alterations in a customized panel of genes relevant for BC will be analyzed. Secondary objectives include the evaluation of: serum thymidine kinase 1 activity over time as blood marker of early response; ctDNA alterations across different patient profiles and clonal evolution of ctDNA alterations under treatment; ctDNA alterations at time of tumor progression; correlation between mutational status detected in ctDNA and matched tissue samples; features of tumor microenvironment before and after treatment; association of pharmacogenomics patterns with adverse events and clinical outcomes. Clinical efficacy and safety of ribociclib + letrozole will be correlated with all biological endpoints. Statistical methods: the study is descriptive in nature and no formal statistical testing is necessary or applicable. Sample size is aligned with other biomarker studies and is based on a feasibility analysis of the trial and relative timelines. Present accrual: The first study patient was screened in Feb 2018, as in June 2018, 126 patients have been screened and 78 patients have been enrolled. Citation Format: De Laurentiis M, Arpino G, Bianchini G, Malorni L, Castelletti D, De Vecchi R, Grasso D. A phase IIIb, open-label, loc","PeriodicalId":19476,"journal":{"name":"Ongoing Clinical Trials","volume":"32 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"85588995","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}