Ongoing Clinical Trials最新文献

{"title":"Abstract OT1-02-02: A phase 1, first-in-human, multi-part study of RAD140, an oral nonsteroidal selective androgen receptor modulator, in postmenopausal women with hormone receptor positive breast cancer","authors":"E. Hamilton, N. Vidula, Cynthia X. Ma, P. LoRusso, J. Saeh, V. Reichert, Ziyang Yu, M. Annett, A. Weitzman, G. Hattersly, A. O'Neill, A. Weise","doi":"10.1158/1538-7445.SABCS18-OT1-02-02","DOIUrl":"https://doi.org/10.1158/1538-7445.SABCS18-OT1-02-02","url":null,"abstract":"Background: Hormone receptor-positive (HR+) breast cancer accounts for about 75% of breast cancer cases. Despite initial response to ER-targeted therapies, subsequent tumor progression remains an important clinical problem, highlighting the need for new therapies with activity in endocrine-resistant tumors. The androgen receptor (AR) is expressed in up to 90% of ER+ breast cancers, and until the 1970s, breast cancer was commonly treated with androgens with single-agent response rates ranging from 20% to 25%. However, androgen-based therapy for breast cancer declined due to lack of tissue selectivity, potential for aromatization to estrogen, and the emergence of ER-targeted agents such as tamoxifen. RAD140 is an oral nonsteroidal selective androgen receptor modulator (SARM) that cannot be converted to estrogen by aromatase. RAD140 has high AR affinity and target selectivity, demonstrating marked tissue-selective AR agonist activity comparable to natural androgens in breast cancer cells, but lacking agonist activity in prostate cancer cells. Preclinical efficacy studies in multiple in vivo and in vitro models of AR+/ER+ breast cancer demonstrate potent anti-tumor activity of RAD140 as a single agent and in combination with a CDK4/6 inhibitor. This first-in-human study will evaluate the safety, tolerability, pharmacokinetics (PK) and clinical activity of RAD140 in patients with HR+ breast cancer. Trial Design and Specific Aims: This is a Phase I, open-label dose escalation and safety expansion study of RAD140 in postmenopausal patients (pts) with advanced HR+ breast cancer for whom no standard therapy is available. During dose escalation (Part A), pts are assigned sequentially to escalating doses of RAD140 using a standard 3+3 design to establish a maximum tolerated dose (MTD) and/or recommended dose (RD) based on safety, PK and preliminary clinical activity. The Safety Expansion (Part B) will further evaluate the safety, tolerability and clinical activity of the RD. Eligibility Criteria: Pts must be post-menopausal females ≥18 years old with locally advanced or metastatic ER+/HER2- (Part A) or ER+/AR+/HER2- (Part B) breast cancer and ECOG 0 or 1. Part A pts must not be eligible for standard therapy. Pts in Part B must have had at least 1 line of prior systemic therapy in the metastatic setting and at least 6 months of prior endocrine therapy in the metastatic setting and progressed on the most recent endocrine therapy. Measurable disease by RECIST 1.1 is also required for enrollment in Part B. Statistical Methods: Descriptive statistics (including mean, standard deviation, median for continuous variables; frequency counts and percentages for categorical variables) will be presented by dose. Plasma or serum PK parameters for RAD140 will be estimated using non-compartmental methods. Present Accrual and Target Accrual: The study will enroll up to 40 pts, including up to approximately 24 pts enrolled in cohorts of 3 to 6 in Part A, and another 15 pts e","PeriodicalId":19476,"journal":{"name":"Ongoing Clinical Trials","volume":"431 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"77492539","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 OT1-01-01: The NEO-LET-EXE-trial: An intra-patient cross-over trial to explore the \"lack of cross-resistance\" between steroidal and non-steroidal aromatase inhibitors","authors":"N. Bahrami, T. Sauer, M. Loeng, B. Gravdehaug, S. Engebretsen, B. Aljabri, V. Bemanian, J. Lindstrøm, T. Lüders, V. Kristensen, J. Geisler","doi":"10.1158/1538-7445.SABCS18-OT1-01-01","DOIUrl":"https://doi.org/10.1158/1538-7445.SABCS18-OT1-01-01","url":null,"abstract":"","PeriodicalId":19476,"journal":{"name":"Ongoing Clinical Trials","volume":"58 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"79221257","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 OT3-04-01: Nivolumab or capecitabine or combination therapy as adjuvant therapy for triple negative breast cancer (TNBC) with residual disease following neoadjuvant chemotherapy: The OXEL study","authors":"K. Khoury, C. Isaacs, M. Gatti-Mays, R. Donahue, J. Schlom, Hongkun Wang, C. Gallagher, D. Graham, R. Warren, A. Dilawari, S. Swain, P. Pohlmann, F. Lynce","doi":"10.1158/1538-7445.SABCS18-OT3-04-01","DOIUrl":"https://doi.org/10.1158/1538-7445.SABCS18-OT3-04-01","url":null,"abstract":"Background: Long-term follow-up of neoadjuvant studies demonstrates poor clinical outcomes in patients with TNBC who do not achieve pathologic complete response, with only 35% remaining free of recurrence at 10 years. The addition of adjuvant capecitabine in the CREATE-X study prolonged disease free survival and overall survival (OS) in patients with HER2 negative breast cancer with residual invasive disease, with more striking benefit in patients with TNBC. Checkpoint inhibitors have not been approved in breast cancer yet, but recent studies suggest a benefit in combination with chemotherapy and low burden of disease. In the current study, we will evaluate the role of chemoimmunotherapy in the adjuvant setting for patients with TNBC with residual disease after neoadjuvant therapy. We will also investigate the role of the peripheral immunoscore (PIS) in predicting the benefit of immune checkpoint inhibition with or without chemotherapy. Trial design: OXEL is a pilot open-label three arm randomized study of nivolumab, capecitabine or the combination as adjuvant therapy for 45 patients with residual TNBC after adequate neoadjuvant chemotherapy. Patients enrolled will be randomly assigned to 1 of 3 treatment arms: nivolumab 360 mg iv q3weeks for x 6 cycles; capecitabine 1250mg/m2 po bid D1-D14 q3 weeks x 6 cycles; nivolumab 360mg iv q3weeks + capecitabine 1250mg/m2 po bid D1-D14 q3 weeks x 6 cycles. Main eligibility criteria: Patients ≥18 years of age with TNBC and ≥1cm of residual disease in the breast and/or node positive disease; receipt of neoadjuvant taxane +/- anthracycline, or platinum, and having completed definitive resection of primary tumor, with no prior use of capecitabine, fluorouracil or immunotherapy, and with no active autoimmune disease or chronic use of systemic steroids. Specific aims: The primary endpoint is assessing the immunologic effects of capecitabine, nivolumab or the combination in the adjuvant setting by PIS. Additional endpoints include toxicity assessment, distant recurrence free survival (DRFS) and OS at 3-years, association between changes in PIS and circulating tumor DNA at different timepoints with clinical outcome variables and characterization of the immune contexture in residual tumors. Statistical methods: The study is designed to assess the change in PIS at 6 weeks from baseline in each arm. The sample size of 15 per arm (45 total for 3 arms) will provide preliminary results. A sample size of 15 per arm will have 85% power to detect an effect size of 1 (the difference of the change in PIS from baseline to week 6 between two arms divided by the standard deviation) at 5% significance level. Present accrual and target accrual: The Institutional Review Board at Georgetown University Medical Center has approved the study. Clinicaltrials.gov NCT03487666. Enrollment of the first patient is expected in July 2018 with a total of 45 patients planned to be recruited. Recruitment sites are MedStar Georgetown University H","PeriodicalId":19476,"journal":{"name":"Ongoing Clinical Trials","volume":"49 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"82370560","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 OT3-05-01: A randomized double-blind phase III clinical trial of neoadjuvant chemotherapy (NAC) with atezolizumab or placebo in patients (pts) with triple negative breast cancer (TNBC) followed by adjuvant atezolizumab or placebo: NSABP B-59/GBG 96-GeparDouze","authors":"C. Geyer, S. Loibl, P. Rastogi, S. Seiler, J. Costantino, V. Nekljudova, P. Cortazar, P. C. Lucas, C. Denkert, E. Mamounas, C. Jackisch, N. Wolmark","doi":"10.1158/1538-7445.SABCS18-OT3-05-01","DOIUrl":"https://doi.org/10.1158/1538-7445.SABCS18-OT3-05-01","url":null,"abstract":"Background: TNBC is associated with higher percentages of pathological complete response (pCR) to neoadjuvant chemotherapy (NAC), and women with a pCR have a favorable prognosis. However, Liedtke (2008) and Loibl (2017) found that women with residual disease have a substantially higher risk of recurrence than women with other subtypes of breast cancer. Additionally, Adams (2017) and Schmid (2017) found that therapeutic blockade of PD-L1 binding by atezolizumab has resulted in relevant anti-tumor efficacy. Methods: Design This is a phase III, double blind, placebo-control trial evaluating neoadjuvant atezolizumab with NAC followed by adjuvant atezolizumab in TNBC. Pts are stratified by region (North America; Europe), tumor size (1.1-3.0cm; >3.0cm), AC/EC schedule (q2w; q3w), and nodal status (positive; negative), then randomized 1:1 to receive atezolizumab/placebo 1200 mg IV every 3 wks concurrently with both sequential regimens of weekly paclitaxel 80 mg/m2 IV for 12 doses with every 3-wk carboplatin AUC of 5 IV for 4 doses followed by AC/EC every 2-3 wks (per investigator discretion) for 4 cycles. Following surgery, pts resume atezolizumab/placebo 1200 mg IV every 3 wks as adjuvant therapy for 6 months. Radiotherapy based on local standards is co-administered with atezolizumab/placebo. Eligibility criteria Centrally-confirmed ER-neg, PR-neg, HER2-neg invasive breast cancer by ASCO/CAP guidelines. Primary tumor must be stage T2 or T3 if cN0 or cN1 with negative biopsy or T1c, T2, or T3 if cN1 with positive biopsy or cN2 or cN3. LVEF >55% and no significant cardiac history. Statistical methods Co-primary endpoints are event-free survival (EFS) and pCR breast/nodes. Secondary endpoints include pCR breast, overall survival, distant disease-free survival, safety and toxicity. Trial is an academic collaboration between NSABP and GBG with support from Genentech/Roche. NCT03281954 Support: Genentech/Roche Citation Format: Geyer, Jr. CE, Loibl S, Rastogi P, Seiler S, Costantino JP, Nekljudova VN, Cortazar P, Lucas PC, Denkert C, Mamounas EP, Jackisch C, Wolmark N. A randomized double-blind phase III clinical trial of neoadjuvant chemotherapy (NAC) with atezolizumab or placebo in patients (pts) with triple negative breast cancer (TNBC) followed by adjuvant atezolizumab or placebo: NSABP B-59/GBG 96-GeparDouze [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 OT3-05-01.","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":"84943053","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 OT2-05-01: FAMILY: A randomized, multicenter, open-label, phase III trial of fulvestrant versus capecitabine as maintenance therapy after first-line combination chemotherapy in patients with hormone receptor-positive, human epidermal growth factor receptor-2 negative metastatic breast cance","authors":"H. Yao, W. Wu, L. Ding, Y. Yu, Yongsheng Wang, Yi Zeng, J. Zhao, Qiao Li","doi":"10.1158/1538-7445.SABCS18-OT2-05-01","DOIUrl":"https://doi.org/10.1158/1538-7445.SABCS18-OT2-05-01","url":null,"abstract":"Background: Metastatic breast cancer (MBC) is incurable. Although first-line endocrine therapy is preferred to hormone receptor positive (HR+), human epidermal growth factor receptor-2 negative (HER2-) MBC, combination chemotherapy should be reserved as the initial treatment for patients with rapid clinical progression, life-threatening visceral metastases, and need for rapidly symptom control. Either prolonged chemotherapy or endocrine therapy may be used as maintenance after disease control. However, which maintenance strategy is superior in terms of delaying disease progression as well as maintaining quality of life (QOL) remains uncertain. This phase III trial aims to compare the efficacy and safety of fulvestrant or capecitabine as maintenance therapy after first-line combined chemotherapy in HR+/HER2- MBC. Trial Design: FAMILY is a multicenter, randomized, open-label phase III trial for HR+ and HER2- MBC. Eligible participants are randomized (1:1) to receive capecitabine (2000mg/m2 twice daily x 14 days followed by 7 days off) or fulvestrant (500mg Days 0, 14, 28, then every 28 days) until disease progression, unacceptable toxicity, or patient refusal. Stratification factor for randomization is sensitivity to adjuvant hormonal therapy (disease-free interval ≤24 months vs. >24 months). Eligibility Criteria: Eligible patients must have HR+ (ER and/or PR>1%, by IHC) and HER2- MBC; achieved a complete or partial response or stable disease (investigator assessed) after 4-8 cycles of first-line combination chemotherapy. Patients with central nervous system metastasis and/or prior use of endocrine therapy for advanced breast cancer are excluded. Specific Aims: The primary endpoint is progression free survival (PFS). Secondary endpoints include overall survival, overall response rate, disease control rate, safety and QOL. A prospective translational research is also planned to assess the correlations between biomarkers and response. Statistical Design: The planned sample size of 256 patients provides approximately 80% of power to detect a 6 months difference of PFS using a log-rank test with two-sided alpha of 0.05. Target Accrual: Recruitment is ongoing. Up to 256 evaluable subjects will be enrolled within 24 months. (ChiCTR-IIR-17014036). Citation Format: Yao H, Wu W, Ding L, Yu Y, Wang Y, Zeng Y, Zhao J, Li Q. FAMILY: A randomized, multicenter, open-label, phase III trial of fulvestrant versus capecitabine as maintenance therapy after first-line combination chemotherapy in patients with hormone receptor-positive, human epidermal growth factor receptor-2 negative metastatic 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 OT2-05-01.","PeriodicalId":19476,"journal":{"name":"Ongoing Clinical Trials","volume":"94 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"85224056","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 OT1-04-01: 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 OT2-03-01: Multicenter study to standardize and evaluate the efficacy of radiofrequency ablation therapy for early breast cancer (RAFAELO study)","authors":"T. Kinosita, M. Takahashi, T. Fujisawa, N. Yamamoto, H. Doihara, S. Ohtani, M. Futamura, K. Aogi, T. Hojo, M. Yoshida, S. Shiino, H. Tsuda","doi":"10.1158/1538-7445.sabcs18-ot2-03-01","DOIUrl":"https://doi.org/10.1158/1538-7445.sabcs18-ot2-03-01","url":null,"abstract":"","PeriodicalId":19476,"journal":{"name":"Ongoing Clinical Trials","volume":"93 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"75498452","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 OT1-03-02: CICLADES: Monitoring ofESR1,PIK3CAandAKT1ctDNA mutations during real-life follow-up of patients with advanced breast cancer treated with endocrine therapy","authors":"V. Massard, L. Uwer, J. Salleron, M. Deblock, A. Kieffer, M. Ríos, P. Gilson, A. Lesur, A. Harlé, J. Merlin","doi":"10.1158/1538-7445.SABCS18-OT1-03-02","DOIUrl":"https://doi.org/10.1158/1538-7445.SABCS18-OT1-03-02","url":null,"abstract":"Activating ESR1 mutations have recently been reported as a key mechanism leading to Aromatase Inhibitor (AI) resistance. ESR1 mutations occur rarely in primary breast cancers. However, in large retrospective studies, ESR1 mutations occurred in up to 39% of Estrogen-Receptor(ER)-positive metastatic breast cancer resistant to AI. Numerous hotspot mutations have been identified, most of them affecting the ligand-binding domain (LBD) and leading to ligand-independent activation of the ER and to resistance to AI. Phosphatidylinositol 3-kinase (PI3K)/AKT pathway is involved in key Cellular Mechanisms and mutations in PIK3CA and AKT1 are frequently reported in breast cancer. In this study, we propose to use a capture-based Next Generation Sequencing (NGS) assay and to use the barcoding and polishing features in our analysis pipeline. This assay will be able to detect all mutations on AKT1 , PIK3CA , ESR1 and other genes on circulating tumor DNA (ctDNA) extracted from blood samples of patients with breast cancer. We consider that this exon-screening strategy is relevant according to the recent knowledge. We plan to prospectively include women with advanced breast cancer about to begin standard-of-care first line endocrine therapy (ET). Patients will be required to have histologically confirmed ER-positive, HER2-negative breast cancer and documented loco-regionally advanced or metastatic disease, not amenable to surgery or radiation with curative intent. Patients with endocrine sensitive disease (no prior ET or relapse more than 12 months after completing adjuvant ET) as well as patients with endocrine resistant disease (relapse while on adjuvant ET or within 12 months of completing adjuvant ET) will be enrolled. ET can be prescribed alone or in combination with a targeted therapy. Nevertheless, we will recruit at least 25% of patients with exclusive ET in the endocrine sensitive group. Peripheral-blood samples, for analysis of ctDNA, will be obtained from participating patients at pre-specified time points: at start of ET to determine the baseline mutational status of ESR1 , PIK3CA , AKT1 and other genes included in a panel of genes of interest in solid tumors, and then, at evaluation of response to therapy until disease progression or end of study. Patients will be followed for 36 months or until disease progression. Determination of progression will be done per local investigator. The primary objective is to describe the prevalence of activating ESR1 mutations affecting the LBD, using NGS, from the start of ET to progression or end of study. Secondary objectives include to describe the prevalence of ESR1 mutations affecting other domains, the prevalence of ESR1 mutations in patients with and without endocrine resistance at enrolment and the prevalence of PIK3CA and AKT1 mutations, to demonstrate that ESR1 , PIK3CA and AKT1 mutations whatever their times of onset are predictors of progression free survival. As of June 2018, 8 sites were opened to recrui","PeriodicalId":19476,"journal":{"name":"Ongoing Clinical Trials","volume":"11 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"85210185","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 OT2-07-04: A phase 1b study of poziotinib in combination with T-DM1 in women with advanced or metastatic HER2-positive breast cancer","authors":"G. Bhat, D. Potter, J. Bharadwaj, N. Khan, L. Shabazz, J. Tache, Zandong Yang","doi":"10.1158/1538-7445.SABCS18-OT2-07-04","DOIUrl":"https://doi.org/10.1158/1538-7445.SABCS18-OT2-07-04","url":null,"abstract":"Background:Poziotinib represents a new class of irreversible quinazoline inhibitors of ErbB receptor tyrosine kinases that inhibit the proliferation of tumor cells in culture and in vivo by inhibiting HER-1 (EGFR), HER-2, HER-4. ErbB signaling plays important roles in the progression of HER2+ breast cancer. Poziotinib has promising clinical activity in breast cancer, and other solid tumors including lung, gastric, and colorectal cancers. Study SPI-POZ-101, is being conducted to evaluate the safety and efficacy of the combination of daily poziotinib and T-DM1, HER2 antibody-drug-conjugate every three weeks in patients with HER2+ advanced or metastatic breast cancer. Trial Objectives and Design: The primary objectives of the study are to determine the maximum tolerated dose (MTD) or maximum administered dose (MAD) of daily poziotinib plus T-DM1 (every 3 weeks) in women with advanced or metastatic HER2 positive breast cancer; and to evaluate the Objective Response Rate (ORR) in these patients. The secondary objectives include disease control rate (DCR), progression-free-survival (PFS), safety and pharmacokinetics at the MTD/MAD dose level of poziotinib plus T-DM1. In Part 1, the dose of poziotinib plus standard dose of T-DM1 (3.6 mg/kg IV) on Day 1 of each cycle will be determined using a “3+3” design with up to 3 escalating dose levels, 8, 10 and 12 mg with no DLT or to de-escalate to 6 mg with DLT observed in Cycle 1. Patients in current dose cohort, if not discontinued, will continue treatment until discontinuation of therapy. In Part 2 of the study, approximately 10 patients will be treated at the MTD/MAD to confirm dose for safety of the combination and to evaluate preliminary efficacy. Eligibility Criteria: The study will enroll female patients between 18 and 90 years with confirmed HER2 overexpression or gene-amplified tumor via immunohistochemistry [IHC] with IHC 3+ or IHC 2+ with confirmatory fluorescence in situ hybridization [FISH]+ or [ISH]+ and must have had at least 2 lines of anti-HER2 directed therapies either in the metastatic or early-stage disease setting. Patients must have adequate hematologic, hepatic, cardiac and renal functions and have at least one measurable lesion per RECIST 1.1 criteria. Exclusion criteria includes unstable CNS metastases or seizure disorder; anticancer chemotherapy, TKIs, biologics, immunotherapy, radiotherapy, or investigational treatment within 15 days; ≥ Grade 2 adverse events; known hypersensitivity to receptor tyrosine kinase inhibitors or any of the components of poziotinib tablets or T-DM1 IV solution. Statistical Methods: Part 1 of the study will enroll 3 to 6 patients at each dose using 3+3 design. Part 2 will enroll 10 patients at the MTD/MAD. The efficacy analysis will be conducted using the Evaluable Population based on RECIST 1.1. The Clopper-Pearson 95% confidence interval will be estimated using exact method based on binomial distribution. Target Accrual:Part 1: 6-18 patients Part 2: 10 pa","PeriodicalId":19476,"journal":{"name":"Ongoing Clinical Trials","volume":"401 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"85229419","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}