bluuebunny/crossref_metadata_2025_split huggingface dataset:
Randomized phase II clinical trial to assess MUC1 specific immune response to L-BLP25 vaccine in addition to standard therapy in newly diagnosed high-risk prostate cancer.
Authors: Singh Nishith K. , Bilusic Marijo , Kim Joseph W. , Heery Christopher Ryan , Falk Martin H. , Wood Bradford J , Pinto Peter A. , Dahut William L. , Kaushal Aradhana , Couvillon Anna , Rauckhorst Myrna , Choyke Peter L. , Turkbey Ismail B. , Trepel Jane B. , Tsang Kwong Yok , Schlom Jeffrey , Gulley James L. , Madan Ravi A. 
Published: March 2020

TPS4701 Background: In high-risk prostate cancer, radiation therapy (RT) + androgen deprivation therapy (ADT) improve survival. Nonetheless, 10-year disease specific mortality is about 25%. L-BLP25 is a cancer vaccine containing the BLP25 lipopeptide that targets MUC1 tumor antigen. It may enhance immune targeting of cells that express MUC1 (e.g. prostate cancer). In murine models, RT synergizes with vaccine-induced anti-cancer immunity (augments T-cell mediated cancer cytolysis, up-regulates cellular Fas and co-stimulatory/adhesion molecules). ADT augments T-cell trafficking to prostate. Immune response to combining the three (L-BLP25 + RT + ADT) is not known. The current trial intends to study this immune response to L-BLP25 + RT + ADT and compare it to RT+ADT alone. Using ELISPOT, endo-rectal MRI and serial prostate biopsies, this trial was designed to correlate systemic immune response with changes in tumor imaging and/or tumor microenvironment after treatment with L-BLP25. This trial may provide insight into immune response biomarkers that are most appropriate in this setting. Methods: A randomized (1:1), open-label, phase II trial of 42 pts is planned. Eligibility: Adult males with newly diagnosed high-risk prostate cancer (T3 or Gleason ≥ 8 or seminal vesicle involvement or N1 or PSA>20) and HLA-A2/A3 positivity (to allow for ELISPOT analysis). The vaccine arm will receive RT + 2-year ADT + L-BLP25. Standard arm will receive RT + 2-year ADT. L-BLP25 vaccine schedule: biweekly X 5 starting with neo-adjuvant ADT, then 6 weekly X 4 starting with RT. A single 300mg/m2 cyclophosphamide infusion (decreases suppressor T-cells) will be given 3 days before L-BLP25 to enhance immune response in the vaccine arm. The impact of L-BLP25 + RT+ADT on MUC-1-specific systemic immune response will be determined using interval peripheral blood ELISPOT assays. Endo-rectal coil MRI will be done before and after treatment to study prostate signal changes for correlative and predictive analysis. MRI-UltraSound guided lesion-targeted serial prostate biopsies will be obtained to assess immune response in tumor microenvironment. Two pts have been enrolled.
A phase III trial of adjuvant chemotherapy following chemoradiation as primary treatment for locally advanced cervical cancer compared to chemoradiation alone: The OUTBACK TRIAL.
Authors: Mileshkin Linda R. , Narayan Kailash , Moore Kathleen N. , Rischin Danny , Trimble Edward Lloyd , Stockler Martin R. , King Madeleine , Kolodziej Ilka , Martyn Julie , Friedlander Michael , Quinn Michael , Shrivastava Shyam K , Small William , Thomas Gillian , Craighead Peter S , Gebski Val ,   Gynecologic Cancer Intergroup
Published: March 2020

TPS5116 Background: Cervical cancer is a global health problem and the most common cause of cancer-related death among women in developing nations. Despite the recently developed cervical cancer vaccine, many women will continue to die from cervical cancer for many decades unless existing treatments can be improved. Unscreened women often present with locally-advanced disease that has a 5 year overall survival (OS) rate of 60% or less following standard chemo-radiation. Although some evidence suggests that adjuvant chemotherapy following chemo-radiation may be of value, its role remains controversial. Methods: OUTBACK is a randomized phase III Gynecologic Cancer InterGroup (GCIG) trial designed and led by the Australia New Zealand Gynaecological Oncology Group (ANZGOG) in collaboration with the NHMRC Clinical Trials Centre. Participating countries (groups) include Australia and New Zealand (ANZGOG), India, the USA and Canada (GOG, RTOG). OUTBACK is suitable for women with locally advanced cervical cancer (FIGO stage IB1 and node positive, IB2, II, IIIB or IVA). The primary objective is to determine if the addition of adjuvant chemotherapy to standard cisplatin-based chemo-radiation improves OS. Women are randomized to either A) standard cisplatin-based chemo-radiation or B) standard cisplatin-based chemo-radiation followed by 4 cycles of carboplatin and paclitaxel chemotherapy. Secondary objectives are to compare progression-free survival, treatment-related toxicity, patterns of disease recurrence, quality of life and psycho-sexual health, and the association between radiation protocol compliance and outcomes. Blood and tumour samples are collected from consenting patients for future translational studies. 780 women will be enrolled to determine if the addition of adjuvant chemotherapy can improve the 5-year OS rate by ≥ 10%. OUTBACK opened in Australia and New Zealand in 2011. In early 2012 the trial opened in the USA and activation of GOG sites is ongoing. 15 patients have been randomized. It is expected that RTOG and India will open the trial later this year with recruitment increasing substantially once all sites are activated.
BOLERO-1: A randomized, phase III, double-blind, placebo-controlled multicenter trial of everolimus in combination with trastuzumab and paclitaxel as first-line therapy in women with HER2-positive (HER2+), locally advanced or metastatic breast cancer (BC).
Authors: Hurvitz Sara A. , Andre Fabrice , Burris Howard A. , Toi Masakazu , Buyse Marc E. , Sahmoud Tarek , Mukhopadhyay Pabak , Massacesi Cristian , Taran Tanya , Ko Jennifer , Rupin Matthieu 
Published: March 2020

TPS648 Background: Up to 25% of BCs overexpress human epidermal growth factor receptor 2 (HER2). Patients with HER2+ disease have a higher rate of relapse and shorter overall survival (OS). Trastuzumab, a monoclonal antibody targeting HER2, is the standard of care and improves OS for HER2+ BC, but acquired resistance is common. The combination of trastuzumab and paclitaxel has shown good tolerability and excellent objective response rates (ORR) in up to 84% of patients with HER2+ metastatic BC (MBC) (Gasparini G, et al. BCRT. 2007;101:355-65). Everolimus is an orally bioavailable inhibitor of mammalian target of rapamycin (mTOR), a protein kinase central to multiple protein synthesis pathways and implicated in trastuzumab resistance. Everolimus-containing regimens have shown promising results in patients with ER+, HER2– advanced BC in phase II/III trials; everolimus plus trastuzumab/paclitaxel or vinorelbine has shown encouraging ORR with an acceptable safety profile in phase I/II trials in patients with HER2+ MBC. The present phase III study was undertaken to assess the effectiveness of adding everolimus to first-line standard therapy in HER2+ advanced BC. Methods: Women with HER2+, locally advanced or metastatic BC who have received no prior systemic therapy (except endocrine) are eligible. Local disease must not be amenable to resection with curative intent. Women with a history of central nervous system metastasis are excluded. Patients are randomized 2:1 (everolimus vs control) to receive standard therapy (paclitaxel and trastuzumab) plus everolimus (10 mg daily) or placebo. The primary endpoint is progression-free survival. Secondary endpoints include OS, ORR, and clinical benefit rate. Additional endpoints are safety, performance status, and biomarkers. This trial is sponsored by Novartis Pharmaceuticals and is registered (ClinicalTrials.gov: NCT00876395). Enrollment began September 2009, with a planned accrual of 717. The current accrual is 719, and the estimated primary completion date is October 2012.
LUX-breast 1: Randomized, phase III trial of afatinib and vinorelbine versus trastuzumab and vinorelbine in patients with HER2-overexpressing metastatic breast cancer (MBC) failing one prior trastuzumab treatment.
Authors: Harbeck Nadia , Im Seock-Ah , Huang Chiun-Sheng , Im Young-Hyuck , Xu Binghe , Hurvitz Sara A. , Lee Keun-Seok , Ahn Jin-Hee , Mehta Ajay O. , Arora Rajender Singh , Sun Qiang , Qin Shukui , Jacob Linu Abraham , Jassem Jacek , Staroslawka Elzbieta , Sufliarsky Jozef , Wojtukiewicz Marek , Lahogue Annick , Uttenreuther-Fischer Martina Maria , Piccart-Gebhart Martine J. ,   on behalf of the LUX-Breast 1 Study Group
Published: March 2020

TPS649 Background: Afatinib is an ErbB Family Blocker that irreversibly blocks signaling from all relevant ErbB Family dimers. Afatinib is being developed in EGFR (ErbB1)-driven (NSCLC/HNSCC) and HER2 (ErbB2)-driven (breast) malignancies. In trastuzumab-resistant, HER2-positive (SUM190) xenografts, afatinib showed antitumor activity which was superior to lapatinib and increased by addition of IV vinorelbine. Afatinib monotherapy also demonstrated clinical activity (progression-free survival [PFS] = 15.1 wk; objective response [OR] = 10%) in an open-label, single-arm, Phase II trial in patients with HER2-positive MBC after progression on trastuzumab. Methods: LUX-Breast 1 (NCT01125566) is a Phase III, open-label, multicenter trial evaluating the efficacy and safety of afatinib + vinorelbine vs. trastuzumab + vinorelbine in patients with HER2-overexpressing MBC who progressed on, or after one prior trastuzumab-based treatment regimen. Patients are randomized 2:1 to afatinib (40 mg/d oral) + vinorelbine (IV 25 mg/m2/wk) or trastuzumab (IV 2 mg/kg/wk after 4 mg/kg loading dose) + vinorelbine (IV 25 mg/m2/wk). Patients receive continuous treatment in the absence of disease progression or adverse events. Key eligibility criteria include histologically-confirmed HER2-positive BC, stage IV disease; no prior treatment with vinorelbine or HER2-targeted treatment other than trastuzumab; progression on one prior trastuzumab based regimen in either the adjuvant (or <12 months after trastuzumab completion) or first-line (or <6 months after trastuzumab completion) setting; prior anthracycline and/or taxane chemotherapy; ECOG score 0 or 1. The primary endpoint is PFS and secondary endpoints include OR, overall survival and safety. Serum and tissue biomarkers will be assessed on archival tissue. HER-receptor and HER-ligand reprogramming, putative resistance markers and EGFR response signature will be explored in fresh tissue biopsies. Enrollment began in June 2010 and is ongoing, targeting >240 sites with a recruitment target of 780 patients.
A phase II trial of trabectedin (T) in patients with hormone receptor-positive, HER2-negative advanced breast cancer, according to xeroderma pigmentosum gene (XPG) expression.
Authors: Awada Ahmad , Cortes Javier , Martin Miguel , Aftimos Philippe , Oliveira Mafalda , Espie Marc , Lardelli Pilar , Extremera Sonia , Kahatt Carmen Maria , Fernandez-Garcia Eva , Delaloge Suzette 
Published: March 2020

TPS652 Background: Hormone receptor-positive, HER2-negative breast cancer (BC) is currently associated with 3-4 years overall survival in the metastatic setting and, after ≥2 relapses, therapeutic approaches are reduced. XPG expression is frequently modified in BC. T is a cytotoxic agent that forms a complex with the XPG, inducing cell apoptosis. As a single agent, T has shown anti-tumor activity in patients with poor prognosis BC, and a better response to T in BC patients with XPG RNA overexpression has been observed. Methods: This is an open-label, phase II study of T (1.3 mg/m2 in 3-hour intravenous infusion every 3 weeks) in patients with hormone receptor-positive, HER2-negative advanced BC, according to their primary tumor’s XPG expression. Primary endpoint: to evaluate the efficacy of T in terms of progression free survival rate at 4 months (PFS4) according to the patient’s XPG expression. Secondary endpoints: Comparison of PFS, overall response rate, duration of response, overall survival and safety profile in XPG-high and XPG-low patients. Assignment: BC patients who have previously received anthracyclins and/or taxanes and who progressed after 2-5 chemotherapy lines will be assigned according to their XPG expression from paraffin embedded tumor samples to stratum A (XPG-high [>3]) or to stratum B (XPG-low [≤3]) (threshold was selected from median XPG expression values observed in a previous trial). Statistical methods: A two-stage design was chosen: at a first stage 20 patients will be enrolled in each stratum. A futility analysis (O’Brien Fleming boundary) based on the primary endpoint (PFS4) will be conducted once 40 evaluable patients have been recruited. If ≥ 7 out of 20 patients achieve PFS4, recruitment will continue to a maximum sample size of 50 evaluable patients per stratum. If ≥ 22 out of 50 patients achieve PFS4, T will be considered active in this group (alpha error: 0.025, power: 80%). To date, 35 patients (16 XPG-high and 15 XPG-low) have been enrolled from three countries and five centers. Recruitment is ongoing.
A combination of pertuzumab, trastuzumab, and vinorelbine for first-line treatment of patients with HER2-positive metastatic breast cancer: An open-label, two-cohort, phase II study (VELVET).
Authors: Perez Edith A. , Lopez-Vega Jose Manuel , Del Mastro Lucia , Petit Thierry , Mitchell Lada , Pelizon Christina H. , Andersson Michael 
Published: March 2020

TPS653 Background: Pertuzumab (P) is a humanized monoclonal antibody directed against the dimerization domain of HER2: it prevents HER2 heterodimerization and thus activation of downstream signaling. Since P targets a different epitope than trastuzumab (H), a more comprehensive HER2 blockade is achieved by combining the two agents. Data from CLEOPATRA showed improved efficacy for P and H plus docetaxel. The combination of P and H has not yet been assessed with other chemotherapy partners in the metastatic setting. H plus vinorelbine (V) has shown comparable efficacy to H plus docetaxel but with a superior safety profile. VELVET will assess the overall response rate (ORR) of P with H+V in first-line patients (pts) with HER2-positive MBC. Co-administration of P and H within the same infusion bag will also be investigated as this could increase pt convenience by reducing administration and observation time. Methods: VELVET is a multicenter, open-label, two-cohort, Phase II trial. Pts with HER2-positive LABC or MBC not previously treated in the metastatic setting with non-hormonal anticancer therapy are eligible. Pts must have an LVEF >55% at baseline and an ECOG PS of 0 or 1. Study enrollment started in January 2012. A total of 210 pts will be included. Based on statistical assumptions, 95 pts must be evaluable per cohort, which assumes a withdrawal rate around 10%. Pts in Cohort 1 (the first 105 pts enrolled) will receive P and H sequentially and pts in Cohort 2 (the next 105 pts) will receive P and H in the same infusion bag at Cycle 2 onwards if drug administration in Cycle 1 was well tolerated. V will be given in both cohorts. Treatment duration is until disease progression or unacceptable toxicity. Study dose: P: 840 mg loading dose, 420 mg q3w (iv); H: 8 mg/kg loading dose, 6 mg/kg q3w (iv), and V: 25 mg/m2 Day 1 and 8 (first cycle) then 30−35 mg/m2 Day 1 and 8 q3w (iv) (dose escalation at investigator’s discretion). The primary endpoint is ORR by independent assessment. Secondary endpoints include investigator assessment of ORR, time to response, duration of response, PFS, time to progression, overall survival, safety and tolerability, and QoL.
LCCC 1025: A phase II study evaluating the mTOR inhibitor everolimus with trastuzumab and vinorelbine to treat progressive HER2-positive breast cancer brain metastases.
Authors: Anders Carey K. , Deal Allison Mary , Dees Elizabeth Claire , Irvin William Johnson , Muss Hyman Bernard , Noe Jeanne , Karginova Olga , Adamo Barbara , Prat Aleix , Carey Lisa A. 
Published: March 2020

TPS656 Background: HER2+ breast cancer (BC) is an aggressive subset of BC with high rates of brain metastases (BM) and poor survival. A recent study illustrates activation of the PI3K/mTOR pathway in approximately two-thirds of BCBM across all subtypes. Everolimus, a novel oral derivative of rapamycin that selectively inhibits mTOR, is clinically-active in combination with trastuzumab (with or without chemotherapy) in advanced HER2+ BC. Everolimus penetrates the blood brain barrier. We are evaluating the efficacy and safety of everolimus plus trastuzumab and vinorelbine in patients (pts) with HER2+ BCBM. Methods: Pts with HER2+ BCBM progressing following cranial radiation and measuring > 0.5cm are eligible for enrollment. Treatment with prior vinorelbine or mTOR inhibition is prohibited. Steroid treatment is allowed if stable or decreasing doses ≥7 days prior to study entry. Pts with leptomeningeal disease are excluded. Pts receive everolimus (5mg orally daily), trastuzumab 2mg/kg and vinorelbine 25mg/m2 (both IV days 1, 8, 15) of a 21 day cycle. Intra- and extracranial disease is assessed every 9 weeks by gadolinium-enhanced brain MRI and CT chest/abdomen/pelvis, respectively. The primary endpoint is intracranial response rate (RR) assessed by modified RECIST. Secondary objectives include extracranial RR (assessed by RECIST 1.1), intra- and extracranial time to progression, progression free survival, overall survival, quality of life, and correlative science endpoints. Statistical considerations: In this two stage design, a sample size of 28 evaluable pts (n=11 in Stage 1) has 80% power to detect a difference between the null (≤5% intracranial RR) and alternative hypothesis (>5%) at a 0.05 significance level. If 1 pt has a CR, PR or SD for ≥ 3 months in the 1st stage, 17 additional pts will be enrolled. Assuming a 20% drop-out rate, 35 total pts will be enrolled. Correlative studies: Archival primary and/or metastatic tissues are required from all pts to evaluate intrinsic BC subtype, protein (p-AKT, pS6, PTEN) and gene expression to identify biomarkers that may be predictive of response or resistance to this novel combination (NCT01305941).
Dasatinib plus SMO antagonist versus dasatinib alone for treating patients (pts) with newly diagnosed Philadelphia chromosome-positive (Ph+) chronic myeloid leukemia in chronic phase (CML-CP): Design of CA180-363, a phase II, open-label randomized trial.
Authors: Trudel Geralyn C. , Paliwal Prashni , Lainas Ioannis 
Published: March 2020

TPS6634 Background: Dasatinib 100 mg once daily (QD) is approved as first-line therapy for pts with newly diagnosed Ph+ CML-CP and those who are resistant or intolerant to prior therapy, including imatinib, based on demonstrated efficacy and tolerability. BMS-833923 (SMO antagonist), selectively blocks hedgehog (Hh) pathway signaling by binding to and antagonizing Smoothened (SMO), preventing downstream signaling and activation of target genes. In preclinical studies, SMO loss or inhibition reduces hematopoietic stem cell renewal, induces CML stem cell depletion, and inhibits imatinib-resistant CML cell growth (Dierks, Cancer Cell 2008; Zhao, Nature 2009). In pts with CML, Hh signaling genes (Sonic hedgehog, SMO, and Gli1) are significantly upregulated compared with control pts (Long, J Exp Clin Cancer Res 2011), suggesting that drug resistance and disease recurrence may be overcome by targeting the Hh signaling pathway. Methods: CA180-363 is a phase 2 trial to assess dasatinib activity with or without SMO antagonist in pts with newly diagnosed Ph+ CML-CP. Pts receive dasatinib 100 mg QD for 12 months and are then randomized 1:1 to continuing dasatinib 100 mg QD with or without SMO antagonist up to 24 months, followed by dasatinib 100 mg QD alone until end of study (60 months). Randomization is stratified by Sokal score at diagnosis and major molecular response (MMR) at 12 months (yes/no). Eligible pts are aged ≥18 years, have an Eastern Cooperative Group (ECOG) performance status of 0-2, and previously untreated Ph+ CML-CP diagnosed within 6 months of enrollment. Primary endpoint (evaluated in pts who do not achieve MMR prior to randomization) is comparison of MMR rates for dasatinib alone vs dasatinib plus SMO antagonist. Other endpoints (evaluated in all pts) are complete molecular response, progression-free survival, event-free survival, transformation-free survival, and safety of the combination regimen. Recruitment started in September 2011 (14 pts enrolled to date); estimated primary completion date is November 2014. ClinicalTrials.gov ID: NCT01357655.
Prospective, observational registry of branded imatinib (IM) and nilotinib (NIL) exposure in pregnant women: Voluntary post-authorization safety study.
Authors: Juma Matthews , Ericson Solveig , Eng Dawn Fun , Acharya Sandip , Wariabharaj Darshan , Owugah Tina , Avenia Bettine , Zernovak Oleg 
Published: March 2020

TPS6638 Background: Family planning decisions for cancer patients of childbearing age are impacted by their diagnosis. IM and NIL are category D drugs (demonstrated risk to the fetus based on mechanism of action and findings in animals; however, the benefits of therapy may outweigh the potential risk to the fetus); women should be advised not to become pregnant when taking these drugs. Limited data exist concerning safety of these drugs during pregnancy and consequences of interrupting treatment. The registry does not recommend patients receiving IM or NIL become pregnant, but serves only to document exposures that occur, and collect information on pregnancy outcome, maternal course of disease, and infant follow-up. Methods: The registry intends to enroll 150 women (≥18 years) treated with branded IM and NIL within 6 mo before or during pregnancy (generic IM and NIL reports are excluded). Schedule of visits and treatment is according to local standard of care. Women are divided into 2 exposure cohorts: 1) pregnancy/fetal: received tyrosine kinase inhibitors (TKIs) within 14 d of conception or at any time during pregnancy; 2) interrupted TKI: received TKIs within 6 mo before conception but interrupted TKIs in preparation for/due to pregnancy. To identify signals of teratogenicity, the registry uses a general population baseline rate of birth defects, and the prevalence of defects in cohorts 1 and 2 may be compared. Cases are quantitatively analyzed for the emergence of unique defects or patterns of defects. Primary objective: monitor TKI-exposed pregnancies to estimate the prevalence of birth defects (calculated by dividing number of birth defects by total number of exposed live births from cohort 1). Secondary objectives are to: 1) determine the impact of treatment interruption on maternal disease status; 2) assess and estimate the prevalence of serious adverse pregnancy outcomes; and 3) assess and estimate the prevalence of developmental delays and functional deficits among infants during the first year of life. Maternal disease status is analyzed, comparing disease status at registration, pregnancy outcome, and 1 y after birth, stratified by length of TKI interruption.