Ongoing Clinical Trials最新文献

{"title":"Abstract OT2-09-02: A phase I dose escalation study of topical bexarotene in women at high risk for breast cancer","authors":"Ps Thomas, Abu T. Patel, A. Contreras, Diane D. Liu, J. Lee, S. Khan, L. Vornik, E. Dimond, M. Perloff, B. Heckman-Stoddard, P. Brown","doi":"10.1158/1538-7445.SABCS18-OT2-09-02","DOIUrl":"https://doi.org/10.1158/1538-7445.SABCS18-OT2-09-02","url":null,"abstract":"Background: Breast cancer prevention with anti-estrogens, including tamoxifen, raloxifene, and exemestane, has been shown to reduce the incidence of hormone receptor-positive breast cancer. However, agents that can reduce the incidence of hormone receptor negative breast cancer are currently lacking. Rexinoids such as bexarotene are vitamin A analogues that have been shown to be involved in cell differentiation, growth, and apoptosis. In preclinical mouse models that develop ER-negative breast cancers, bexarotene showed a significant reduction in mammary tumor development. Oral bexarotene has been evaluated in BRCA mutation carriers and significant decreases in cyclin D1 were noted in breast cells suggesting biological activity of bexarotene on breast tissue. Systemic side effects of hyperlipidemia and hypothyroidism were also found. Data from chemoprevention studies with topical 4-hydroxytamoxifen support the concept of topical agents penetrating into the breast tissue and exhibiting biological activity in the tissue. We hypothesize that topical bexarotene can be applied to the breast as a chemoprevention agent with penetration to the breast tissue without subsequent systemic side effects and toxicity as seen with oral bexarotene. Trial Design: Women at high risk for breast cancer will be recruited and assigned to one of three different dose levels: 10mg (1ml) every other day, 10mg (1ml) daily, 20mg (2ml) daily to one unaffected breast for 4 weeks. The primary endpoint of the study is to determine the recommended phase II dose of topical bexarotene 1% gel for evaluation in healthy at-risk women. Dose Limiting Toxicity (DLT) is defined as a grade 2 skin adverse event that persists for at least 6 days or any grade 3 or greater adverse event related to the study drug. A grade 2 skin adverse event that recurs and persists for at least 3 days is also a DLT. The Maximum Tolerated Dose (MTD) will be defined as the highest dose level at which no more than 2 participants experience a DLT among 10 participants treated. A conservative modification of the standard “3+3” design will be applied. The first three participants will be assigned to the lowest dose level. New cohorts of 3-4 participants will not be treated until toxicity has been fully evaluated for all current participants through 4 weeks. Once the MTD has been determined, an expansion cohort of an additional 10 patients will be recruited at the MTD to further evaluate safety and toxicity at this dose level as well bexarotene concentration in the breast tissue. Secondary endpoints include serum bexarotene level, tissue bexarotene levels, and changes in thyroid function tests, lipid profile, and calcium. The planned accrual for this study if maximally accrued to all dose levels and the dose expansion cohort will be 40 participants. Citation Format: Thomas PS, Patel AB, Contreras A, Liu DD, Lee JJ, Khan S, Vornik LA, Dimond EP, Perloff M, Heckman-Stoddard BM, Brown PH. A phase I dose escalation stud","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":"80812051","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 OT1-01-06: 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, M. Colleoni, C. Saura, J. Kroep, E. Warner, A. Gombos, AB Sætersdal, M. Ruggeri, R. Gelber, Z. Sun","doi":"10.1158/1538-7445.sabcs18-ot1-01-06","DOIUrl":"https://doi.org/10.1158/1538-7445.sabcs18-ot1-01-06","url":null,"abstract":"","PeriodicalId":19476,"journal":{"name":"Ongoing Clinical Trials","volume":"295 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"77009581","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Abstract OT1-12-02: Biomarker study of patients with HER2-negative metastatic breast cancer receiving combination therapy with nivolumab, bevacizumab and paclitaxel as first-line treatment (WJOG9917BTR)","authors":"Y. Ozaki, S. Kitano, Koji Matsumoto, Maiko Takahashi, T. Mukohara, M. Futamura, N. Masuda, J. Tsurutani, K. Yoshimura, H. Minami, T. Takano","doi":"10.1158/1538-7445.SABCS18-OT1-12-02","DOIUrl":"https://doi.org/10.1158/1538-7445.SABCS18-OT1-12-02","url":null,"abstract":"Background : In recent years, anti-PD-1 antibody, an immune checkpoint inhibitor, has been developed for the treatment of various types of cancer, including breast cancer. Synergistic effects of nivolumab, paclitaxel and bevacizumab are expected, based on various preclinical data, when these drugs are administered in combination. A biomarker study is ongoing to evaluate the immune status of patients participating in the NEWBEAT trial, which is a phase II trial of nivolumab + paclitaxel + bevacizumab therapy as first-line treatment for patients with metastatic or recurrent HER2-negative breast cancer. Methods : HER2-negative breast cancer patients from the WJOG9917B (NEWBEAT) trial are enrolled in this biomarker study. To explore new biomarkers for combined treatment of breast cancer with immune-checkpoint inhibitors and anti-vascular endothelial growth factor antibodies, we propose to conduct multicolor immunohistochemistry (IHC) assays for immunomonitoring of the intra-tumor environment, such as the expressions of PD-L1, CD4 and CD8. Blood samples are collected before the start of treatment and at four time-points during the treatment, to determine, using a multicolor flow cytometry panel, the numbers of circulating immunosuppressive cells, such as regulatory T cells, myeloid-derived suppressor cells and tumor-associated macrophages (M2). In the NEWBEAT trial, patients receive nivolumab 240 mg/body on days 1 and 15, paclitaxel 90 mg/m2 on days 1, 8 and 15, and bevacizumab 10 mg/kg on days 1 and 15 every 4 weeks until disease progression. The primary endpoint is the objective response rate, and the key secondary endpoints include progression-free survival, overall survival, and toxicity of the protocol treatment. A total of 51 patients will be enrolled and the enrollment period will be one year. This trial opened to accrual in February 2018. Clinical trial registry number: UMIN000029590 Citation Format: Ozaki Y, Kitano S, Matsumoto K, Takahashi M, Mukohara T, Futamura M, Masuda N, Tsurutani J, Yoshimura K, Minami H, Takano T. Biomarker study of patients with HER2-negative metastatic breast cancer receiving combination therapy with nivolumab, bevacizumab and paclitaxel as first-line treatment (WJOG9917BTR) [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 OT1-12-02.","PeriodicalId":19476,"journal":{"name":"Ongoing Clinical Trials","volume":"7 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"75231736","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 OT2-07-05: A phase III trial to compare eribulin mesylate + trastuzumab (H) + pertuzumab (P) with paclitaxel or docetaxel + HP for HER2-positive advanced or metastatic breast cancer (JBCRG-M06/ EMERALD)","authors":"N. Masuda, T. Yamashita, S. Saji, K. Araki, Yoshinori Ito, T. Takano, M. Takahashi, J. Tsurutani, K. Koizumi, M. Kitada, Y. Kojima, Y. Sagara, H. Tada, T. Iwasa, T. Kadoya, T. Iwatani, H. Hasegawa, S. Morita, S. Ohno","doi":"10.1158/1538-7445.SABCS18-OT2-07-05","DOIUrl":"https://doi.org/10.1158/1538-7445.SABCS18-OT2-07-05","url":null,"abstract":"Background: Docetaxel + Trastuzumab (H) + Pertuzumab (P) provided progression-free survival (PFS) and overall survival (OS) benefits in HER2-positive advanced or metastatic breast cancer (AMBC) in the CLEOPATRA study as a first-line therapy. However, long-term administration of docetaxel at a dose of 75 mg/m2 every 3 weeks in AMBC patients (pts) is difficult due to the toxicities. Eribulin mesylate (E) is a well-tolerated microtubule inhibitor, and we have reported the efficacy and safety of EHP regimen as first- and second-line therapy for AMBC in a multicenter, phase II study (JBCRG-M03/UMIN000012232). In this M06 study, we address the clinical question as to which is the better chemotherapy partner for HP as first line regimen, in terms of efficacy, toxicity and QOL. Methods: JBCRG-M06 is a multicenter open-label randomized phase III study for HER2-positive AMBC pts who have received no prior chemotherapy except for the HER2- Antibody-Drug Conjugate (ADC). Pts will be randomized 1:1 to E (1.4mg/m2 on day 1 and 8) + H (8 mg/kg loading dose followed by 6 mg/kg) +P (840 mg loading dose followed by 420 mg) q3wks or standard taxanes (docetaxel 75mg/m2 on day1 or paclitaxel 80mg/m2 on day 1, 8 and 15) + HP q3wks. Stratification factors for randomization are; presence of visceral metastases, number of prior taxanes on perioperative adjuvant treatment, and treatment with prior anti-HER2-ADC. Primary endpoint is PFS and secondary endpoints include overall response rate, duration of response, OS, patient-reported outcomes (PRO) relating to QOL and peripheral neuropathy, new-metastases free survival, and safety. Translational research to search for biomarker for individual precision therapy will be performed. Main eligibility criteria are as follows: pts with HER2-positive AMBC, female aged 20-70 years old, ECOG PS of 0-1, LVEF ≥ 50% at baseline and adequate organ function. Pts who had progressive MBC within 6 months after the end of primary adjuvant systemic chemotherapy are excluded. The sample size was calculated by type1 error (2-sided) of 0.05 and 80% power to estimate the noninferiority margin 1.33 with an expected median PFS of 14.2 months. The target number of pts is 480 recruited over the duration of 3-years. The first patient in was achieved on August 2017. (ClinicalTrials.gov Identifier:NCT03264547). Citation Format: Masuda N, Yamashita T, Saji S, Araki K, Ito Y, Takano T, Takahashi M, Tsurutani J, Koizumi K, Kitada M, Kojima Y, Sagara Y, Tada H, Iwasa T, Kadoya T, Iwatani T, Hasegawa H, Morita S, Ohno S. A phase III trial to compare eribulin mesylate + trastuzumab (H) + pertuzumab (P) with paclitaxel or docetaxel + HP for HER2-positive advanced or metastatic breast cancer (JBCRG-M06/ EMERALD) [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 OT2-07-05.","PeriodicalId":19476,"journal":{"name":"Ongoing Clinical Trials","volume":"75 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"74808898","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 OT2-01-03: A prospective pilot study of simultaneous robotic assisted nipple sparing mastectomy and immediate reconstruction","authors":"Jae Seok Lee, H. Park, Joo Hang Kim, Dw Lee, Sy Song, D. Lew, J.-H. Kim, S. Kim, Y. Cho, H. Lee, Kb Lee, K. Yoon","doi":"10.1158/1538-7445.SABCS18-OT2-01-03","DOIUrl":"https://doi.org/10.1158/1538-7445.SABCS18-OT2-01-03","url":null,"abstract":"","PeriodicalId":19476,"journal":{"name":"Ongoing Clinical Trials","volume":"28 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"84464792","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: Multi-institution phase II trial of intraoperative electron beam radiotherapy boost at the time of breast conserving surgery with oncoplastic reconstruction in women with early-stage breast cancer","authors":"J. Bazan, J. Stephens, D. Agnese, R. Skoracki, K. Arneson, J. Reiland, G. Gupta, K. Gallagher, S. McElroy, N. Gupta, J. White","doi":"10.1158/1538-7445.sabcs18-ot2-04-04","DOIUrl":"https://doi.org/10.1158/1538-7445.sabcs18-ot2-04-04","url":null,"abstract":"","PeriodicalId":19476,"journal":{"name":"Ongoing Clinical Trials","volume":"48 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"82159802","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 OT2-01-04: Towards omitting breast cancer surgery in patients with pathologic complete response after neoadjuvant systemic therapy: The MICRA trial (minimally invasive complete response assessment)","authors":"M. E. M. Noordaa, F. V. Duijnhoven, C. Loo, A. V. Loevezijn, E. Werkhoven, K. Vijver, T. Wiersma, H. Winter-Warnars, G. Sonke, M. Peeters","doi":"10.1158/1538-7445.SABCS18-OT2-01-04","DOIUrl":"https://doi.org/10.1158/1538-7445.SABCS18-OT2-01-04","url":null,"abstract":"Background Improvements in neoadjuvant systemic therapy (NST) for breast cancer patients have led to increasing rates of pathologic complete response (pCR). Breast-conserving surgery (BCS) after NST is considered safe, despite the fact that the original tumor bed is not entirely excised. It can therefore be hypothesized that breast surgery could be omitted in patients achieving pCR. However, since imaging modalities are insufficiently accurate to predict pCR after NST, the need for surgery is unchanged. The MICRA trial is designed to determine the value of ultrasound guided biopsy of the breast in identifying pCR after NST. The ultimate aim of our study is to eliminate surgery of the breast in patients achieving pCR, consequently improving quality of life of these patients. Trial design The MICRA trial is a multi-center observational prospective cohort study. Inclusion and exclusion criteria are presented in table 1. In all patients receiving NST, a marker is placed in the center of the tumor area pre-NST. Magnetic resonance imaging (MRI) is performed pre-NST and just before or after the last course of NST. Patients with radiologic complete response (rCR; complete absence of pathologic contrast enhancement) or partial response (rPR, 0.1-2.0 cm residual contrast enhancement, ≥30% decrease in tumour size) are eligible for participation. In these patients, 8 ultrasound guided biopsies are obtained in the region surrounding the marker: 4 central ( Statistical analysis and accrual The primary endpoint of the trial is the false-negative rate (FNR) of the biopsy procedure. If the true FNR is 3%, 130 patients without pCR in specimen are sufficient to show that the FNR does not exceed 8% using a one-sided binomial test with a significance α-level of 0.05. With an expected average pCR rate of 65%, 375 patients with rCR will be included. In the rPR-group the expected pCR rate is 12% and therefore 150 patients will be included. In total 525 patients will be included. Until now, 144 patients have been included. Conclusion The ultimate aim of the MICRA trial is to eliminate surgery of the breast in patients achieving pCR, by identifying pCR with use of ultrasound guided biopsy. In this scenario, local therapy in patients with pCR would be restricted to radiotherapy. Citation Format: van der Noordaa ME, van Duijnhoven FH, Loo CE, van Loevezijn A, van Werkhoven E, van de Vijver KK, Wiersma T, Winter-Warnars HA, Sonke GS, Vrancken Peeters M-JT. Towards omitting breast cancer surgery in patients with pathologic complete response after neoadjuvant systemic therapy: The MICRA trial (minimally invasive complete response assessment) [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr OT2-01-04.","PeriodicalId":19476,"journal":{"name":"Ongoing Clinical Trials","volume":"40 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"84652276","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 OT1-05-03: Efficacy and safety of scalp cooling device for prevention of alopecia in patients with breast cancer","authors":"A. Kodera, K. Ogura, A. Hattori, H. Yukawa, Shiho Sakaguchi, A. Matsuoka, N. Tanaka, M. Kamimura, N. Jibiki, Y. Naritaka, A. Hirano","doi":"10.1158/1538-7445.SABCS18-OT1-05-03","DOIUrl":"https://doi.org/10.1158/1538-7445.SABCS18-OT1-05-03","url":null,"abstract":"Background Chemotherapy for breast cancer causes alopecia as a side effect. Some patients refuse chemotherapy because of alopecia, resulting in the omission of a standard therapy. It is believed that a scalp cooling device can prevent alopecia by promoting vasoconstriction of the scalp and reducing exposure of the hair root cells to anticancer agents. There are phenotypic differences of the efficacy of a scalp cooling device for alopecia. In fact, a Dutch scalp cooling registry reported that the success rate of scalp cooling was 51% in European women and 33% in Asian women. Therefore, we aimed to investigate the efficacy of scalp cooling device for chemotherapy-induced alopecia among Asian women with breast cancer. Trial design This is a phase II trialto evaluate the efficacy and safety of scalp cooling device for risk reduction of alopecia in women with stage I/II/III breast cancer treated with adjuvant/neoadjuvant chemotherapy in a single institute. Eligibility criteria Women diagnosed with Stage I to III breast cancer who are scheduled to receive preoperative or postoperative adjuvant chemotherapy containing anthracycline and/or taxanes are enrolled. Patients who have blood malignancies (leukemia, non-Hodgkin lymphoma, other systemic lymphoma), and cold allergy, are excluded. Specific aims The primary endpoint is the proportion of patients with Common Terminology Criteria for Adverse Events (CTCAE) grade 0-1 alopecia after the completion of all cycles of chemotherapy (success rate). Secondary endpoints are safety, quality of life, use of wig or cap, and success rates after the completion of all cycles of chemotherapy distinguished by anthracycline(AC) and taxane. The cooling device is the Paxman scalp cooling system. Scalp cooling was performed from 30 mins before initiation until 90 mins (25 min for taxane) after chemotherapy. Pictures of the scalp were taken at the time of the initiation of each course. Statistical methods Successful treatment was defined as the presence of less than 50% of hair-loss area. The sample size was calculated using the Simon method, with a type I error of 10% (two-sided) and a study power of 80%.The expected success rate is 30%, with a threshold success rate of 10%, and the required number of patients was estimated to be 19. Present and target accrual Patient accrual was started in April 2018 and present accrual is 3. We plan to enroll a total of 20 patients in the trial. Citation Format: Kodera A, Ogura K, Hattori A, Yukawa H, Sakaguchi S, Matsuoka A, Tanaka N, Kamimura M, Jibiki N, Naritaka Y, Hirano A. Efficacy and safety of scalp cooling device for prevention of alopecia in patients with breast cancer [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr OT1-05-03.","PeriodicalId":19476,"journal":{"name":"Ongoing Clinical Trials","volume":"80 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"90870779","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 OT1-01-07: PIONEER- Pre-operative wIndOw study of letrozole plus PR agonist megestrol acetate versus letrozole aloNE in post-menopausal patients with ER-positive breast cancer","authors":"S. Kumar, J. Benson, S. McIntosh, P. King, G. Dougall, A. Kateb, A. Vallier, L. Jones, W. Qian, E. Provenzano, C. Caldas, P. Pantziarka, J. Carroll, R. Baird","doi":"10.1158/1538-7445.SABCS18-OT1-01-07","DOIUrl":"https://doi.org/10.1158/1538-7445.SABCS18-OT1-01-07","url":null,"abstract":"Background: Published preclinical findings provided new insights into the functional 9cross-talk9 between the oestrogen receptor (ER) and the progesterone receptor (PR) in breast cancer (BC) (Mohammed et al., Nature, 2015). Addition of a PR agonist to anti-oestrogens directly modifies ERa chromatin binding and the transcriptional response in breast cancer cells, and is anti-proliferative in vitro and in vivo . Megestrol Acetate (MA), an off-patent semi-synthetic derivative of progesterone, has been licensed for many years as treatment for ER+ metastatic BC. There is also good evidence for the effectiveness of MA as a supportive therapy to ameliorate endocrine therapy-related hot flushes. Trial design: PIONEER is a three-arm, open label, multi-centre randomized phase II pre-surgical window trial evaluating effects of 15 days of preoperative therapy with Letrozole (LET), or LET plus MA 40mg, or LET plus MA 160mg in postmenopausal women with ER+ HER2- invasive primary BC. Eligibility criteria: Inclusion Criteria Postmenopausal women with histologically confirmed invasive BC, ≥T1c, clinical NX or N0-N3, ER+ (Allred≥3), and HER2- 2 groups of patients are potentially eligible: Cohort A: Patients whose cancers have been deemed to be operable by the Multi-Disciplinary Team (MDT) with surgery planned for the next 2-6 weeks Cohort B: Patients with early or locoregionally advanced BC planned for primary endocrine therapy either in lieu of surgery or as neoadjuvant therapy before surgery\u0000 ECOG performance status of 0-2 Adequate Liver, Renal, Bone marrow function Exclusion Criteria Hormone replacement therapy in the last 6 months Treatment with tamoxifen or an aromatase inhibitor (AI) in the last 6 months A progestogen-containing intrauterine system in situ, unless removed prior to randomisation Metastatic disease on presentation Recurrent BC (patients with a new primary invasive BC are eligible) S p ecific aims: The primary endpoint is % change in proliferation between baseline and day 15 tumor biopsies, measured by Ki67 IHC assessment. Secondary endpoints include: expression of Aurora Kinase A, Caspase 3 and AR/PR/EMT markers by IHC; and safety endpoints. Exploratory endpoints: transcription factor mapping (ChIP-seq) and identification of differential ERa-associated proteins (RIME) on paired fresh-frozen tumor samples. PIONEER will help determine whether there is value in conducting a Phase III adjuvant study to investigate the longer term benefit of combining an AI with MA, and if so, at what dose (40mg vs. 160mg). Statistical methods: Patients are randomized in a 1:1.5:1.5 ratio into arms A:B:C. Based on results from previous clinical trials, a mean 66% reduction in Ki67 is anticipated for LET alone (arm A), and a 77.5% reduction for the combination arms B and C, based on preclinical data. Present and target accrual: Patients are being recruited in Cambridge, Cornwall, Belfast & London with 6 other UK sites due to open q3/4 2018. At the time of submission","PeriodicalId":19476,"journal":{"name":"Ongoing Clinical Trials","volume":"70 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"77384514","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 OT3-04-04: A randomized phase II study of pembrolizumab in combination with carboplatin versus carboplatin alone in breast cancer patients with chest wall disease, with immunologic and genomic correlative studies","authors":"N. Vidula, A. Goga, Jimmy Hwang, M. Liu, B. Park, R. Nanda, P. Pohlmann, A. Storniolo, A. Brufsky, V. Abramson, H. Rugo","doi":"10.1158/1538-7445.SABCS18-OT3-04-04","DOIUrl":"https://doi.org/10.1158/1538-7445.SABCS18-OT3-04-04","url":null,"abstract":"Background: Thirty percent of patients with breast cancer may experience chest wall recurrence, which is associated with a higher risk of developing distant metastases and a poor prognosis. Cancer cells may evade immune rejection through the programmed cell death 1 (PD-1) pathway. Pembrolizumab, an anti-PD-1 antibody, binds PD-1 and inhibits its interaction with the programmed death ligand 1 (PD-L1) to facilitate tumor immune rejection. We hypothesize that pembrolizumab may be an effective therapy in chest wall recurrence, given the inflammatory nature, and the high expression of PD-1 in tumors with lymphovascular invasion. Platinum agents may enhance anti-tumor immunity in a synergistic manner, and the combination of pembrolizumab and carboplatin has demonstrated efficacy in advanced lung cancer. In this study, the combination of pembrolizumab and carboplatin is being evaluated in breast cancer patients with chest wall disease. Methods: This is a randomized phase II study of breast cancer patients with advanced, unresectable breast cancer involving the chest wall, being conducted through the Translational Breast Cancer Research Consortium (TBCRC). Patients may have hormone resistant disease (at least 2 prior lines of hormone therapy), triple negative breast cancer, or refractory HER2+ disease for enrollment. They may have other sites of distant metastases, have received any number of prior lines of therapy, have had prior surgery, but prior chest wall radiation is not necessary. Eighty-four patients at 7 TBCRC sites will be randomized 2:1 to treatment with pembrolizumab 200 mg IV and carboplatin AUC 5 IV every 3 weeks followed by pembrolizumab 200 mg IV alone every 3 weeks (Arm A, n=56) or carboplatin AUC 5 IV every 3 weeks (Arm B, n=28), with an option for patients in Arm B to cross-over to single agent pembrolizumab 200 mg IV every 3 weeks (arm Bx) on progression. Patients will undergo imaging with CT chest, abdomen, and pelvis at baseline and every 2 cycles of treatment for response evaluation. The primary endpoint is the disease control rate in the chest wall and distant sites at 18 weeks of treatment, and this study is powered to determine a 20% difference in disease control rates between arms A and B (hazard ratio of 0.52, α= 0.10, β= 0.20). After 18 patients are enrolled into Arm B, an interim analysis for futility will be conducted to enable early closure of that arm for lack of efficacy. Secondary endpoints in the study are toxicity, progression free survival, and response based on PD-L1 expression and irRECIST. Exploratory endpoints, which will be studied using peripheral blood testing and chest wall tumor biopsies at baseline and after 2 cycles of treatment, include determining associations of response with changes in tumor and peripheral blood immune composition, soluble PD-L1 expression, circulating tumor cells, cell free DNA, and tumor PD-L1 and MYC genomic expression. Ultimately this study promises to improve our understanding of ","PeriodicalId":19476,"journal":{"name":"Ongoing Clinical Trials","volume":"45 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"88904535","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}