Ongoing Clinical Trials最新文献

{"title":"Abstract OT2-03-04: A trial of induction Talazoparib followed by a combination of Talazoparib and Avelumab in advanced breast cancer: The TALAVE study","authors":"A. Heeke, M. Pishvaian, Hongkun Wang, A. Cohen, J. Schlom, R. Donahue, C. Jochems, M. Gatti-Mays, P. Pohlmann, A. Tan, C. Isaacs, F. Lynce","doi":"10.1158/1538-7445.sabcs19-ot2-03-04","DOIUrl":"https://doi.org/10.1158/1538-7445.sabcs19-ot2-03-04","url":null,"abstract":"Background: Patients with advanced breast cancer (ABC) have recently gained access to promising new therapies, including PARP inhibitors (PARPi) and immunotherapy. However, not all patients benefit from these approaches, with response rates highest in patients characterized by a particular biomarker (ie BRCA1/2 mutation or PD-L1 expression). Combination strategies may be more efficacious than single agents and may induce responses in otherwise non-responders. PARPi activate the STING pathway leading to T cell recruitment and stimulate antigen presentation via increased T cell cytotoxic activity, creating a tumor microenvironment that may be more susceptible to immunotherapy. A number of trials have assessed the antitumor efficacy of this combination, though the optimal drug scheduling and the impact of BRCA1/2 status on the effect of PARP inhibition on immunomodulation are unknown. In the TALAVE study, the PARPi talazoparib is combined with the PD-L1 inhibitor avelumab. Talazoparib is an oral small molecule selective inhibitor of PARP-1/2 with potent in vitro PARP trapping capacity. Avelumab is a human IgG1 anti-PD-L1 monoclonal antibody that prevents the interaction between PD-L1 and PD-1 and allows for an engagement of Fc-γ receptors on NK cells to induce tumor-directed ADCC in vitro. Trial design: This is an open-label, multi-institutional trial (NCT03964532) for patients with ABC. During the phase I portion, 6 patients are enrolled regardless of BRCA1/2 mutation status to assess safety of the combination. A maximum of 24 patients will be enrolled. Eligibility criteria include willingness to undergo serial biopsies and no previous exposure to PARPi or prior disease progression on anti-PD1 or anti-PDL1 therapy or within 6 months of use. Patients will be enrolled to two pre-defined cohorts: cohort 1 - BRCA1/2 mutant and HER2 negative ABC (pre-identified presence of somatic or germline BRCA1/2 deleterious mutation) and cohort 2 - BRCA1/2 wild type and TNBC (patients with previous somatic or germline testing for BRCA1/2 that did not reveal a deleterious mutation). Enrolled patients will receive a 4-week induction of talazoparib (1mg orally daily, D1-D28), followed by a combination of talazoparib and avelumab (800mg IV D1 and D15). To assess the efficacy and immunomodulatory effects of PARP inhibition induction followed by anti-PD-L1 therapy, patients will undergo serial tumor biopsies (baseline, post 4 weeks of talazoparib, post 4 weeks of talazoparib and avelumab and at progression for patients who clearly benefitted from therapy) to assess tumor infiltrating lymphocytes (TILs) and PD-L1 expression. Patients will also undergo serial blood sample collection to gauge the peripheral immunoscore by flow cytometry, including an assessment of the number of immune cells and their function. Specific aims: The primary objective is to evaluate the safety and tolerability of this combination. Secondary objectives includeassessment of anti-tumor efficacy of ","PeriodicalId":19476,"journal":{"name":"Ongoing Clinical Trials","volume":"77 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2020-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"88980590","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 OT3-07-01: Efficacy of magnetic resonance-guided high intensity focused ultrasound for the ablation of breast cancer","authors":"J. Maar, R. Deckers, L. Bartels, T. Dalen, J. Gorp, P. Diest, A. Witkamp, H. Vaessen, Maria NicoleGerardineJohanna Aleida Braat, C. Moonen","doi":"10.1158/1538-7445.sabcs19-ot3-07-01","DOIUrl":"https://doi.org/10.1158/1538-7445.sabcs19-ot3-07-01","url":null,"abstract":"Background: Over the past decades, breast cancer treatment has evolved from extensive disfiguring surgery to less invasive procedures. In patients with small localized tumors breast conserving therapy (BCT) has become the standard of care. However, surgery still involves risks associated with general anesthesia and complications such as bleeding, infection and suboptimal cosmetic results. Conversely, Magnetic Resonance-guided High intensity Focused Ultrasound (MR-HIFU) ablation of breast cancer is an entirely non-invasive procedure that can be performed under procedural sedation and analgesia (PSA). With MR-HIFU, a focused ultrasound beam penetrates through soft tissues and causes localized heating (55-70°C) of a target. Magnetic resonance imaging (MRI) is used for target-identification and real-time temperature-monitoring (MR thermometry). In a previous phase I study in ten breast cancer patients, tumors were deliberately partially ablated and safety and accuracy of a dedicated MR-HIFU breast system (Profound Medical) was shown.1,2 This system’s lateral sonication approach and wide aperture reduce the risk of heating heart, lungs and skin to a minimum.3 In the current study we aim to demonstrate that complete breast tumor ablation with MR-HIFU is feasible. Trial design: Single-arm phase II study in patients with primary breast cancer. We will use a dedicated MR-HIFU breast system (Profound Medical) to ablate breast tumors before BCT or mastectomy, in a treat-and-resect protocol. We will perform MRI before MR-HIFU, during the MR HIFU session and one week after to evaluate radiologic response. Primary endpoint is efficacy, assessed by percentages of necrotic and residual viable tumor. Secondary endpoint is safety, assessed by adverse events and cosmetic changes. Descriptive statistics will be used. Eligibility criteria Non-pregnant, non-lactating women ≥18 years of age, weighing histologically proven invasive breast cancer, cT1-2 N0-2 Mx, subtypes invasive ductal carcinoma or invasive carcinoma ‘not otherwise specified’ / ‘no special type’ a tumor in reach of the HIFU beams, diameter ≤ 3.0 cm and distance ≥1.5 cm to skin, nipple and pectoral wall WHO-Performance Score ≤2 a body size fitting in the MR bore and the ability to lie in prone position no prior treatment with neoadjuvant chemotherapy in the past 3 months no prior radiotherapy, thermal therapy or surgery in the targeted breast no contraindications to PSA, MRI or MRI contrast agents no conditions that may interfere with MR-HIFU such as a pacemaker, scar tissue, breast prosthesis or surgical clips no extensive intraductal components, determined on biopsy Additionally, patients may be excluded when the risk of adjuvant over- or undertreatment (due to performing Bloom and Richardson grading on the tumor biopsy) is considered too high. Target accrual 10 patients (present: 0, IRB approval obtained) Conclusion In this phase II trial we aim to show the feasibility of complete tumor ablation of br","PeriodicalId":19476,"journal":{"name":"Ongoing Clinical Trials","volume":"45 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2020-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"80148256","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 OT1-04-02: POSITIVE: A study evaluating pregnancy, disease outcome and safety of interrupting endocrine therapy for premenopausal women with endocrine responsive breast cancer who desire pregnancy (IBCSG 48-14/big 8-13)","authors":"O. Pagani, A. Partridge, F. Peccatori, H. Azim, C. Shimizu, C. Saura, E. Warner, A. Sætersdal, J. Kroep, M. Ruggeri, R. Gelber","doi":"10.1158/1538-7445.sabcs19-ot1-04-02","DOIUrl":"https://doi.org/10.1158/1538-7445.sabcs19-ot1-04-02","url":null,"abstract":"","PeriodicalId":19476,"journal":{"name":"Ongoing Clinical Trials","volume":"281 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2020-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"76795427","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 OT2-04-04: Neoadjuvant HER2-targeted therapy +/- immunotherapy with pembrolizumab (neoHIP): An open label randomized phase 2 trial","authors":"H. McArthur, J. Leal, D. Page, C. Abaya, R. Basho, Lindsey Ristow, H. Coleman, S. Shiao, S. Knott, M. Mita, M. Tighiouart, A. Chung, F. Dadmanesh, P. McAndrew, S. Karlan, S. Verma, A. Giuliano","doi":"10.1158/1538-7445.sabcs19-ot2-04-04","DOIUrl":"https://doi.org/10.1158/1538-7445.sabcs19-ot2-04-04","url":null,"abstract":"","PeriodicalId":19476,"journal":{"name":"Ongoing Clinical Trials","volume":"24 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2020-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"73082206","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 OT2-07-03: Trastuzumab deruxtecan (DS-8201a) vs ado-trastuzumab emtansine (T-DM1) for subjects with HER2-positive, unresectable and/or metastatic breast cancer who previously received trastuzumab and a taxane: A phase 3, randomized study","authors":"S. Verma, J. Shahidi, C. Lee, K. Wang, J. Cortés","doi":"10.1158/1538-7445.SABCS18-OT2-07-03","DOIUrl":"https://doi.org/10.1158/1538-7445.SABCS18-OT2-07-03","url":null,"abstract":"Background: Ado-trastuzumab emtansine (T-DM1), a HER2-targeted antibody drug conjugate (ADC), is approved for patients with HER2-positive metastatic breast cancer (BC) after disease progression on a trastuzumab-based regimen. Approval of T-DM1 was based on the EMILIA trial in which T-DM1 demonstrated an objective response rate (ORR) of 43.6%, a median progression-free survival (PFS) of 9.6 months, and an overall survival (OS) of 30.9 months (Verma S, et al. NEJM . 2012). DS-8201a is a novel HER2-targeted ADC with a humanized HER2 antibody attached to a topoisomerase I inhibitor payload by a cleavable peptide-based linker, and with a high drug-to-antibody ratio of 7 to 8. In an ongoing phase 1 trial, DS-8201a showed a manageable safety profile and promising antitumor activity in HER2-positive BC previously treated with T-DM1 (confirmed ORR of 54.5%; April 2018 data cutoff) (Iwata et al, ASCO 2018). 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 vs T-DM1 in subjects with HER2-positive (IHC 3+ or IHC 2+/ISH+; confirmed by centralized testing) unresectable and/or metastatic BC previously treated with trastuzumab and a taxane (NCT03529110, DESTINY-BREAST03). Subjects who previously received a HER2-targeted ADC are excluded. Approximately 500 eligible subjects will be randomized (1:1) to receive DS-8201a (5.4 mg/kg) or T-DM1 (3.6 mg/kg) IV once every 3 weeks. Randomization will be stratified by hormone receptor status, prior pertuzumab treatment, and history of visceral disease. For subjects randomized to T-DM1, the treatment will be in accordance with the approved label. The primary efficacy endpoint is PFS based on blinded, independent central review using RECIST v1.1 criteria. Secondary efficacy endpoints include OS, 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 be performed when approximately 331 PFS events have been observed. This will provide 90% power to detect a hazard ratio of 0.70 for PFS with a 1-sided alpha of 0.025, assuming a median PFS with T-DM1 of 9.6 months and that PFS follows an exponential distribution. 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 150 sites851468 including in North America, Europe, and Asia. Citation Format: Verma S, Shahidi J, L","PeriodicalId":19476,"journal":{"name":"Ongoing Clinical Trials","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"75163771","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Abstract OT3-06-01: Phase Ib clinical trial of coPANlisib in combination with Trastuzumab emtansine (T-DM1) in pre-treated unresectable locally advanced or metastatic HER2-positive breAst cancer (BC) “PANTHERA”-CTRIAL-IE 17-13","authors":"A. Hassan, G. Gullo, S. O'Reilly, M. Ruiz-Borrego, S. Toomey, L. Grogan, O. Breathnach, P. Morris, J. Walshe, J. Crown, D. O'mahony, A. Falcón, K. Egan, A. Hernando, A. Teiserskiene, C. Kelly, L. Coate, B. Hennessy","doi":"10.1158/1538-7445.SABCS18-OT3-06-01","DOIUrl":"https://doi.org/10.1158/1538-7445.SABCS18-OT3-06-01","url":null,"abstract":"Background: The phosphoinositide 3 kinase (PI3K) pathway is important in the oncogenic function of HER2. Aberrant activation of PI3K is implicated in resistance to trastuzumab and other HER2-targeted therapies and is frequent, with up to 22% of HER2 positive breast cancer having a PIK3CA mutation. Copanlisib is a pan-class 1 PI3K inhibitor administered i.v. with low nanomolar activity against both PI3Kα and PI3Kβ. Copanlisib has been shown to re-sensitise trastuzumab resistant cell lines to trastuzumab with synergism seen in some cell lines between copanlisib and HER2 targeted therapy. Trial design: This is a phase Ib open label, single arm adaptive, multi-centre trial of copanlisib in combination with T-DM1. Eligible patients will receive T-DM1 at 3.6mg/kg i.v. on day 1 of a 21-day cycle plus copanlisib. Copanlisib will be administered i.v. according to the dose escalation scheme (dose level 1 is 45mg on days 1 and 8, dose level 2 is 60mg on days 1 and 8, dose level 3 is 60mg on days 1, 8, and 15). Dose level -1 will be 45 mg on day 1 in case dose de-escalation is needed. We will enrol 3 to 6 patients per dose level. All patients in each level must have completed at least the first cycle of therapy before enrolment in the next dose level. Patients not completing the first cycle for a reason other than toxicity will be replaced. Dose escalation and determination of the Maximum Tolerated Dose (MTD) will be based on the occurrence of Dose Limiting Toxicities (DLT). Eligibility criteria: Eligible patients are those with unresectable locally advanced or metastatic HER2-positive BC who previously received trastuzumab and a taxane, separately or in combination. Participants must have adequate organ function and ECOG PS ≤ 2 Objectives: The primary objective is to determine the MTD for copanlisib in combination with T-DM1 in patients with pre-treated unresectable locally advanced or metastatic HER2-positive BC. Secondary objectives include evaluating the safety, efficacy and cardiotoxicity in patients treated with this regimen. Exploratory objectives include examining for predictive biomarkers in tumour tissue and blood or plasma and to examine molecular tumour adaptation to clinical trial therapy. Statistical methods : Patients will be accrued in cohorts of 3 patients according to a standard 3+3 algorithm, with dose escalation and determination of MTD based on the occurrence of DLT, using the usual threshold probability of 33%. The final dose level will be expanded to include a total of 6 additional patients (expansion cohort). Present accrual and target accrual: The trial will start accrual in October 2018. Maximum of 24 patients will be enrolled. Citation Format: Hassan A, Gullo G, O9Reilly S, Ruiz-Borrego M, Toomey S, Grogan L, Breathnach O, Morris PG, Walshe JM, Crown J, O9Mahony D, Falcon A, Egan K, Hernando A, Teiserskiene A, Kelly CM, Coate L, Hennessy BT. Phase Ib clinical trial of coPANlisib in combination with Trastuzumab emtansine (T-DM1) in ","PeriodicalId":19476,"journal":{"name":"Ongoing Clinical Trials","volume":"21 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"81507615","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 OT3-03-03: PARTNER: Randomised, phase II/III trial to evaluate the safety and efficacy of the addition of olaparib to platinum-based neoadjuvant chemotherapy in triple negative and/or germline BRCA mutated breast cancer patients","authors":"J. Abraham, A. Vallier, W. Qian, A. Machin, L. Grybowicz, S. Thomas, M. Weiss, C. Harvey, K. McAdam, L. Hughes-Davies, A. Roberts, R. Roylance, E. Copson, K. Pinilla, A. Armstrong, E. Provenzano, M. Tischkowitz, E. McMurty, H. Earl","doi":"10.1158/1538-7445.SABCS18-OT3-03-03","DOIUrl":"https://doi.org/10.1158/1538-7445.SABCS18-OT3-03-03","url":null,"abstract":"Background: No specific targeted therapies are available for Triple Negative Breast Cancers (TNBC), an aggressive and diverse subgroup. The basal TNBC sub-group share some phenotypic and molecular similarities with germline BRCA (gBRCA) tumours. In gBRCA patients, and potentially other homologous recombination deficiencies, these already compromised pathways may allow drugs called PARP inhibitors (Olaparib) to work more effectively. Aims: To establish if the addition of olaparib to neoadjuvant platinum based chemotherapy for basal TNBC and/or gBRCA breast cancer is safe and improves efficacy (pathological complete response (pCR)). Methods:Trial design: 3-stage open label randomised phase II/III trial of neoadjuvant paclitaxel and carboplatin +/- olaparib, followed by clinicians9 choice of anthracycline regimen. Stage 1 and 2: Randomisation (1:1:1) to either control (3 weekly carboplatin AUC5/weekly paclitaxel 80mg/m2 for 4 cycles) or one of two research arms with the same chemotherapy regimen but with two different schedules of olaparib 150mg BD for 12 days. Stage 3: Patients are randomised (1:1) to either control arm or to the research arm selected in stage 2. End-points: Stage 1: Safety; Stage 2: Schedule selection using pCR rate and completion rate of olaparib using a “pick-the-winner” design. Stage 3: pCR rate. Enrichment design is applied with an overall significance level 0.05(α) and 80% power. A total of 527 patients will be included to detect an absolute improvement of 15% (all patients) and 20% (gBRCA patients) by adding olaparib to platinum based chemotherapy. Trial Progress: PARTNER has been recruiting in UK since 27th May 2016. IDSMC recommended to continue the trial without change after reviewing the Stage 1 safety data. The recruitment of stage 2 was completed in April 2018 and results to be reviewed by the IDSMC in early 2019. The trial is open and enrolling patients to national and international sites. Citation Format: Abraham J, Vallier A-L, Qian W, Machin A, Grybowicz L, Thomas S, Weiss M, Harvey C, McAdam K, Hughes-Davies L, Roberts A, Roylance R, Copson E, Pinilla K, Armstrong A, Provenzano E, Tischkowitz M, McMurty E, Earl H. PARTNER: Randomised, phase II/III trial to evaluate the safety and efficacy of the addition of olaparib to platinum-based neoadjuvant chemotherapy in triple negative and/or germline BRCA mutated breast cancer patients [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 OT3-03-03.","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":"82524645","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 OT1-05-01: A pilot study of the combination of entinostat with capecitabine in metastatic and high risk breast cancer after neoadjuvant therapy","authors":"T. Millard, N. Wages, G. Petroni, C. Brenin, P. Dillon","doi":"10.1158/1538-7445.SABCS18-OT1-05-01","DOIUrl":"https://doi.org/10.1158/1538-7445.SABCS18-OT1-05-01","url":null,"abstract":"Background: HDAC inhibitors (HDACi) upregulate thymidine phosphorylase resulting in enhanced conversion of capecitabine to active 5-fluorouracil and in synergistic anti-proliferative effects. HDACi9s down regulate thymidine synthase and may prevent resistance to fluoropyrimidines. Entinostat is a well-tolerated class I HDACi in phase III trials for metastatic breast cancer. Specific Aims: The primary objective is to determine the maximum tolerated dose combination (MTDC) of entinostat and capecitabine in participants with metastatic breast cancer. It is hypothesized that entinostat and capecitabine is a synergistic, safe, and tolerable combination. An expansion phase will assess the safety of the MTDC from Part A in participants with high risk breast cancer after neoadjuvant therapy. The expansion phase will generate a preliminary estimate of disease-free survival. Exploratory objectives include estimates of the association of volume of circulating tumor DNA (ctDNA) and circulating tumor cells (CTCs) with the presence of residual disease and if it decreases following treatment with the combination of entinostat and capecitabine. Trial Design: The dose escalation phase (Part A) will accrue participants with metastatic breast cancer using an adaptive design to determine the MTDC. The starting doses will be entinostat 3mg po weekly and capecitabine 800mg/m2 po bid, 14 days on and 7 days off with 21 day cycles. Patients will be monitored for toxicity and adverse events. The MTDC is defined as the dose combination with DLT rate closest to the target DLT rate of 25%. The expansion phase (Part B) will accrue breast cancer participants with residual invasive disease after neoadjuvant therapy starting at the MTDC estimated in Part A. The adaptive modeling design will be used in Part B to establish the MTDC in this patient population. Participants will be treated with the MTDC for a total of 8 cycles. Blood samples will be obtained from all enrolled patients in the expansion phase prior to the start of adjuvant treatment with entinostat and capecitabine so that ctDNA and CTCs can be measured as correlative studies. Measurements will be repeated at the end of the eighth cycle. Eligibility Criteria: Part A: Dose Escalation Phase: Stage IV breast cancer patients; Receptor Status: hormone receptor positive or negative, triple negative patients; Age: 18 year and older Part B: Expansion Phase: Stage I-III high risk breast cancer patients; Completed at least four cycles of neoadjuvant taxane or anthracycline based chemotherapy; Residual invasive disease (ypT1a or greater) or known positive lymph nodes (ypN0(itc) or greater); Receptor Status: hormone receptor positive or negative, triple negative patients; Age: 18 years and older Statistical Methods: The trial is designed to determine the MTDC, defined by acceptable toxicity of the combination, for two study populations. A Bayesian adaptive design is being used to guide accrual decisions based on the occurrence of","PeriodicalId":19476,"journal":{"name":"Ongoing Clinical Trials","volume":"36 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"87727897","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 OT2-06-04: MORPHEUS: A phase Ib/II trial platform evaluating the safety and efficacy of multiple cancer immunotherapy combinations in patients with hormone receptor–positive and triple-negative breast cancer","authors":"D. Yardley, M. Abu-Khalaf, V. Boni, A. Brufsky, L. Emens, M. Gutierrez, S. Hurvitz, S. Im, S. Loi, McCune Sl, P. Schmid, C. O'Hear, X. Zhang, G. Vidal","doi":"10.1158/1538-7445.SABCS18-OT2-06-04","DOIUrl":"https://doi.org/10.1158/1538-7445.SABCS18-OT2-06-04","url":null,"abstract":"Background: Cancer immunotherapy (CIT) has significantly improved overall survival across multiple tumor types, but only subsets of patients experience durable response with single-agent CIT. Combinations of CIT with targeted therapy or chemotherapy may be needed in order to target multiple cancer immune escape mechanisms simultaneously, thus providing personalized treatment options that extend clinical benefit to more patients. The MORPHEUS platform includes multiple phase Ib/II trials designed to identify early signals of safety and activity of CIT combinations. Using a randomized trial design, multiple CIT combination arms are compared with a single standard-of-care control arm. These trials have the flexibility to open new treatment arms with novel CIT combinations as they become available and to close arms that show minimal activity or unacceptable toxicity. Here we describe MORPHEUS trials in patients with metastatic or unresectable locally advanced hormone receptor–positive (HR+BC) or triple-negative breast cancer (TNBC), 2 patient populations in need of more treatment options. Trial design: MORPHEUS-HR+BC (NCT03280563) will enroll patients with metastatic or unresectable locally advanced HR+BC who have progressed during or after first-line treatment with a cyclin-dependent kinase (CDK) 4/6 inhibitor and whose tumors do not express human epidermal growth factor 2 (HER2). MORPHEUS-TNBC (NCT03424005) will enroll patients with metastatic or unresectable locally advanced TNBC who have progressed during or after first-line treatment with chemotherapy. For both studies, key inclusion criteria include Eastern Cooperative Oncology Group performance status of 0-1 (stage 1) or 0-2 (stage 2) and measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. Key exclusion criteria include prior treatment with T-cell co-stimulating or immune checkpoint blockade therapies, and symptomatic, untreated, or actively progressing central nervous system metastases. Patients in both trials will be randomized to one of the CIT atezolizumab combination arms or a control arm (up to 5 arms in HR+BC and up to 6 arms in TNBC). Patients experiencing loss of clinical benefit or unacceptable toxicity in stage 1 may be eligible to switch to a different CIT atezolizumab combination arm in stage 2. Primary endpoints are safety measures and investigator-assessed objective response rate per RECIST v1.1. Progression-free survival, overall survival, duration of response, clinical benefit rate (HR+BC) or disease control rate (TNBC) are among the secondary endpoints. Exploratory biomarkers will also be examined. Citation Format: Yardley DA, Abu-Khalaf M, Boni V, Brufsky A, Emens LA, Gutierrez M, Hurvitz S, Im S-A, Loi S, McCune SL, Schmid P, O9Hear C, Zhang X, Vidal GA. MORPHEUS: A phase Ib/II trial platform evaluating the safety and efficacy of multiple cancer immunotherapy combinations in patients with hormone receptor–positive and triple-negative breast ca","PeriodicalId":19476,"journal":{"name":"Ongoing Clinical Trials","volume":"76 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"91529742","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Abstract OT2-01-05: A randomized controlled trial comparing post-operative intensive follow-up with standard follow-up in high-risk breast cancer patients (JCOG1204: INSPIRE)","authors":"T. Hojo, N. Masuda, T. Shibata, T. Mizutani, T. Shien, T. Kinoshita, T. Iwatani, C. Kanbayashi, D. Kitagawa, M. Tsuneizumi, H. Iwata","doi":"10.1158/1538-7445.SABCS18-OT2-01-05","DOIUrl":"https://doi.org/10.1158/1538-7445.SABCS18-OT2-01-05","url":null,"abstract":"Background: The standard follow-up after surgery for breast cancer includes periodic interviews, clinical examinations, and mammography, but many institutions are conducting intensive follow-up including periodic computed tomography(CT), magnetic resonance imaging(MRI), and bone scintigraphy in the world, despite the lack of evidence to support this approach. While intensive follow-up may contribute to prolonged survival through earlier diagnosis and treatment of relapse, it has the disadvantages of high effort and costs placed on patients(pts) and healthcare workers, radiation exposure for imaging examinations, and overtreatment owing to false-positive results. Although past two randomized trials could not show significant difference in overall survival (OS), as imaging methods have remarkably improved, leading to the earlier detection of relapse, and medical therapies have remarkably improved in recent years, randomized controlled trials are needed to confirm whether intensive follow-up can really prolong survival sufficiently to offset these disadvantages in high-risk breast cancer pts. Trial design: This study is a multi-institutional two-arm open label randomized controlled phase III trial being conducted with the participation of 42 hospitals belonging to the Breast Cancer Study Group of Japan Clinical Oncology Group. Eligible pts are randomized either to the intensive follow-up group or to the standard follow-up group; the former will undergo physical examination, bone scintigraphy, chest and abdominal CT, brain MRI/CT and frequent tumor markers, whereas the latter will undergo physical examination at the same frequency and tumor markers will be evaluated once a year. Mammography once a year is planned for both groups. This trial has been registered at the UMIN Clinical Trials Registry as UMIN000012429. Eligibility criteria: High-risk breast cancer pts, who are expected to have recurrence rates of over 30% within 5 years after surgery. The main inclusion criteria are as follows: four or more axillary nodal metastases in the estrogen receptor (ER) positive pts without neoadjuvant chemotherapy(NC)., axillary node metastases in ER-negative pts without NC, axillary nodal metastases in ER-positive pts with NC, histologically proven residual invasive cancer in the breast or axilla in ER-negative with NC. Specific Aims: The primary endpoint is OS, and secondary endpoints are disease-free survival, relapse-free survival, distant metastasis–free survival, OS in intrinsic subtypes, actual number of implemented examinations, compliance with pre-specified examinations, and adverse events. Statistical methods: The primary endpoint will require a total of 538 events to be assessed in order to obtain a statistical power of 80% with a one-sided significance level of 0.05. Thus, the planned sample size to compare the two survival curves is set at 1500 pts, assuming an accrual time of 6 years and a follow-up time of 7 years according to the Schoenfeld and R","PeriodicalId":19476,"journal":{"name":"Ongoing Clinical Trials","volume":"50 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"83087722","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}