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 OT1-05-04: Phase 3 trial of carboplatin in triple negative breast cancer (TNBC) patients with residual invasive carcinoma after neoadjuvant chemotherapy (JONIE4:J-CAT trial)","authors":"H. Tanino, M. Suzuki, H. Kaise, M. Miyashita, T. Chishima, M. Hayashi, Y. Miyoshi, M. Futamura, S. Ohtani, M. Nagahashi, T. Ohta, Y. Kosaka, T. Ishikawa, Y. Hasegawa, T. Kubota, T. Sangai, T. Iwatani, A. Yamada, K. Akazawa, N. Kohno","doi":"10.1158/1538-7445.SABCS18-OT1-05-04","DOIUrl":"https://doi.org/10.1158/1538-7445.SABCS18-OT1-05-04","url":null,"abstract":"Background: It is well known that the prognosis of non pCR TNBC patients was poor after anthracycline and taxan treatment. For such patients, capecitabine seems to be effective to reduce recurrence based on the HR 0.58 of the CREATE X trial (Masuda, N. et al. Adjuvant Capecitabine for Breast Cancer after Preoperative Chemotherapy. N Engl J Med. 376, 2147. 2017) . However, the target of capecitabine is still unclear for TNBC. We classified non pCR tumors as BRCAness and Sporadic using BRCAness test(MRC-Holland, Amsterdam, the Netherlands). The recurrence rate of the BRCAness group was about 70%. Carboplatine is expected to be effective against BRCAness tumors, as it is a DNA damaging agent. In this study BRCAness can be checked just before carboplatin treatment using surgical specimens. Then the efficacy of carboplatin will be directly known to make comparison between DFS in the carboplatin group and that of the observation group. Trial design: This is anopen label, randomized phase III study that will enroll TNBC with residual invasive cancer after surgery with preoperative chemotherapy including both anthracycrine and taxan. Patients are randomly assigned to either the carboplatin group or observation group. The patients in the carboplatin group are treated with carboplatin at AUC 6 and those in the observation group are observed at only 3 years. Eligibility criteria: 1) ER and PgR 2) Preoperative chemotherapy including both anthracycrine and taxan. 3) Residual invasive cancer on breast tumors or lymph node metastasis in surgical specimens. 4) 20-79 year old women. 5) No chemotherapy within 5 years. 6) Not bilateral breast cancer, without metastasis, no prior breast cancer. 7) No severe bone marrow suppression. Specific aims:Primary objective is DFS (Disease Free Survival). Secondary objectives are overall survival and safety. STATISTICAL METHODS: The 3 years recurrence rate of the observation group was estimated as 40% and hazard ratio at 0.58 based on the CREATE X trial. For both groups, 135 patients are necessary. This study is powered to approximately 80% to test the superiority of carboplatin group at a 2-sided α=0.05 using a stratified log-rank test. Activation Date:22ndMarch 2018. No patients had been enrolled till 3rd July. Citation Format: Tanino H, Suzuki M, Kaise H, Miyashita M, Chishima T, Hayashi M, Miyoshi Y, Futamura M, Ohtani S, Nagahashi M, Ohta T, Kosaka Y, Ishikawa T, Hasegawa Y, Kubota T, Sangai T, Iwatani T, Yamada A, Akazawa K, Kohno N. Phase 3 trial of carboplatin in triple negative breast cancer (TNBC) patients with residual invasive carcinoma after neoadjuvant chemotherapy (JONIE4:J-CAT trial) [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 OT1-05-04.","PeriodicalId":19476,"journal":{"name":"Ongoing Clinical Trials","volume":"46 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"75273312","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 OT1-06-01: ANG1005 in leptomeningeal disease (ANGLeD) trial: A randomized, open-label, phase 3 study of ANG1005 compared with Physician's Best Choice in HER2-negative breast cancer patients with newly diagnosed leptomeningeal carcinomatosis and previously treated brain metastases","authors":"P. Kumthekar, B. Lawrence, V. Iordanova, N. Ibrahim, R. Mazanet","doi":"10.1158/1538-7445.SABCS18-OT1-06-01","DOIUrl":"https://doi.org/10.1158/1538-7445.SABCS18-OT1-06-01","url":null,"abstract":"Background: Annually, more than 4,000 patients are diagnosed with leptomeningeal carcinomatosis (LC) from breast cancer in the U.S. Since most therapies cannot cross the Blood-CSF-Barrier (BCB) and the Blood-Brain-Barrier (BBB), treatment options for LC are limited to local radiation and few chemotherapy agents, none of which have provided durable clinical benefit, leading to short overall survival (OS) of 3-4 months. ANG1005 is a novel peptide-drug conjugate, consisting of 3 paclitaxel molecules covalently linked to a peptide that targets the LRP-1 receptor to cross both BCB and BBB, and enter the tumor cells, where the paclitaxel is cleaved off to exert its anti-tumor activity. ANG1005 has previously shown in a phase 2 study to prolong OS in LC patients from breast cancer with brain metastases (BM) to 8 months. Trial Design: This is an open-label, multi-center phase 3 randomized study to evaluate the efficacy of ANG1005 in HER2-negative breast cancer patients with newly diagnosed LC and documented history of previously treated BM when compared to Physician Best Choice (PBC). Hundred and fifty (150) patients will be randomized 1:1 to receive either ANG1005 experimental treatment or an Investigator assigned PBC control treatment. ANG1005 will be administered by intravenous (IV) infusion at a starting dose of 600 mg/m2 every 3 weeks. Allowed PBC therapies include capecitabine, eribulin, or high-dose IV methotrexate. CNS disease (LC and BM) will be evaluated at screening and every 6 weeks by MRI, CSF cytology and neurological assessments according to LANO and RANO-BM criteria. Extracranial disease will be evaluated by CT scans according to RECIST at screening and every 6-12 weeks. All patients will be followed for survival every 6-8 weeks from the date of the last dose until death, lost to follow-up or consent withdrawal. Eligibility Criteria: Eligible patients are adults (≥ 18 years old) with HER2-negative breast cancer, newly diagnosed LC and documented history of previously treated BM. Patients must be neurologically stable and have adequate blood counts, organ and bone marrow function with an ECOG status grade ≤2. Patients previously treated with ANG1005 or with known allergy to paclitaxel or its components are excluded. Specific aims: The primary endpoint is OS. Secondary endpoints include CNS (LC and BM) progression-free survival and clinical benefit rate, 6- and 12-month OS rates, LC response rate and duration of response, OS for triple negative patients and safety. Statistical Methods: This study is sized for testing the hypothesis of improved OS for ANG1005 versus PBC in all patients (HR=0.58, two-sided test, overall type 1 error of 5%). Interim analysis for OS (using O9Brien Fleming boundaries for efficacy and a fixed HR=1 for futility) will be performed when a total of 55 death events are reached across both arms. Study Accrual: Target accrual is 150 patients. The study is currently planned to start in the fall of 2018. Citation Format: ","PeriodicalId":19476,"journal":{"name":"Ongoing Clinical Trials","volume":"39 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"80042296","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}