bluuebunny/crossref_metadata_2025_split huggingface dataset:
A phase II multicenter study of the efficacy and safety of sunitinib given on an individualized schedule as first-line therapy for metastatic renal cell cancer.
Authors: Bjarnason Georg A. , Basappa Naveen S. , Knox Jennifer J. , Kollmannsberger Christian K. , Reaume M. Neil Neil , Zalewski Pawel , Macfarlane Robyn Jane , MacKenzie Mary J. , Hotte Sebastien J. , Heng Daniel Yick Chin , Soulieres Denis , Miller Jessie 
Published: March 2020

TPS4594 Background: Retrospective reviews have shown poorer than expected response rate (RR), progression free survival (PFS) and overall survival (OS) in Sunitinib treated (Rx) Renal Cell Cancer (RCC) patients (pts) who experience minimal toxicity. This study is based on an individualized (individ) Rx strategy where dose/schedule modifications (DSM) were done to maximize dose and minimize time off Rx in 172 pts (Bjarnason ASCO-GU 2011). Pts started on 50mg 28 days (d) on/14d off. DSM were done to keep toxicity (fatigue, skin, GI, hematology) at ≤ grade-2. DSM-1 was 50mg 14d/7d with individ increases in d on Rx based on toxicity. DSM-2 was 50mg 7d/7d with individ increases in d on Rx. DSM-3 was 37.5mg continuously with individ 7d breaks. DSM-4 was 25mg continuously with individ 7d breaks.In pts with clear cell histology PFS was inferior (5.8 mo) on the standard 50mg 28d/14d schedule vs. DSM schedules (>14 months, p=0.0002) These data, confirmed in 185 pts at MD Anderson (Jonasch KCA 2012), suggest that pts with minimal toxicity after 28d on Rx may benefit from dose escalation. Methods: A prospective phase II study has opened in 11 centers in Canada. DSM are done as described above. Pts with minimal toxicity after 28d are escalated to 62.5 mg and then 75 mg on a 14d /7d schedule. We expect to dose escalate 25% of pts and maintain another 40% of pts on a 50 mg dose that would otherwise have been dose reduced. The primary objective is the PFS associated with this strategy. Secondary objectives include dose intensity, RR, OS, toxicity, and quality of life. Samples for Sunitinib pharmacokinetics are obtained during the first course and again when the ideal sunitinib schedule has been established. Samples for biomarker and DNA correlative studies are collected. Based on the standard arm of the EFFECT trial (identical eligibility criteria), we assume a median PFS of 8.5 months in pts Rx using standard dosing. We expect pts treated with the indiv dosing will have a median PFS of 14 months. With alpha=0.05, a two-sided, single-arm non-parametric survival test would have over 90% power to detect this difference with a total of 110 pts on study. Study enrollment began in July 2012 with 25 pts currently on study. Clinical trial information: NCT01499121.
A randomized double-blind phase III trial comparing vintafolide plus pegylated liposomal doxorubicin (PLD) versus PLD plus placebo in patients with platinum-resistant ovarian cancer (PROCEED).
Authors: Naumann R. Wendel , Gilbert Lucy , Miller Anthonette M. , Ma Hong , Ghamande Sharad A. , Vergote Ignace 
Published: March 2020

TPS5613 Background: Folate receptor (FR) is expressed on the majority of epithelial ovarian cancers and FR expression appears to be a negative prognostic factor in this setting. Vintafolide (EC145) is a folate-conjugate designed to selectively deliver desacetylvinblastine monohydrazide (DAVLBH) to FR-expressing cells. 99mTc-Etarfolatide (EC20) is a technetium-labeled folate that identifies FR-expressing tumors. In a phase 2 study comparing vintafolide + PLD with PLD alone, the combination demonstrated a statistically and clinically significant delay in PFS (5.0 months) compared with PLD alone (2.7 months) in women with platinum-resistant ovarian cancer (Naumann et al, ASCO 2011). Data also indicated that 99mTc-etarfolatide may have utility for selecting patients most likely to benefit from vintafolide therapy. Methods: This is an international, randomized, double-blind, placebo-controlled phase 3 study of PLD ± vintafolide therapy compared in patients with primary or secondary platinum-resistant ovarian cancer (NCT01170650). Key eligibility criteria include: ≥18 years, pathology-confirmed epithelial ovarian, fallopian tube or primary peritoneal carcinoma, prior platinum-based chemotherapy, a RECIST v1.1 measureable lesion, and ECOG performance status 0 or 1. At baseline, patients undergo 99mTc-Etarfolatide imaging to identify FR-positive lesions and are subsequently randomized to the vintafolide ± PLD. PLD (50 mg/m2) adjusted for Ideal Body weight is administered on day 1 of a 4-week cycle and treatment continues until the maximum allowable cumulative dose (550 mg/m2) is reached or until disease progression or intolerable toxicity. Vintafolide (2.5 mg) or placebo is administered on days 1, 3, 5, 15, 17, and 19 of a 4-week cycle and treatment can continue for up to 20 cycles or until unacceptable toxicity or disease progression. The primary objective is to assess PFS based on investigator assessment (RECIST v1.1) in FR positive patients. Secondary objectives include OS, safety/tolerability, overall response rate, and disease control rate. Enrollment to the study is currently ongoing. Clinical trial information: NCT01170650.
Potentiation of cetuximab by inhibition of Tregs in metastatic squamous cell cancers of head and neck.
Authors: Jha Gautam Gopalji , Miller Jeffrey S 
Published: March 2020

TPS6101 Background: There are few effective treatment options for patients with metastatic squamous cell cancers of head and neck (HNSCC). The only significant advance in the last few decades has been approval of cetuximab, a monoclonal antibody directed against the overexpressed epidermal growth factor receptor (EGFR). Despite its high specificity for EGFR, cetuximab as single-agent has resulted in response rates of only 13% and PFS of less than 2 months. Recent evidence suggests that cetuximab may induce tumor cell killing through an immune-mediated ADCC and not through blockade of EGFR signaling. Cetuximab binds EGFR on tumor cells making them targets for natural killer (NK) cell-mediated lysis. The effectiveness of cetuximab is limited by the tumor mediated immune-suppression that inhibits NK and other effector cells. This local and possibly generalized immune suppression is primarily mediated by regulatory T cells (Tregs) which inhibit NK cells and other effector cells. HNSCC tumors are highly immunosuppressive and characterized by marked and persistent elevation of inhibitory Tregs. The myelosuppression and immunosuppression caused by cyclophosphamide is dose dependent, and at lower doses cyclophosphamide has been shown to selectively deplete Tregs, restore NK cell activity and paradoxically induce auto-immunity. Objectives: To assess potentiation of clinical response by tracking PFS, OS and HRQOL and immune augmentation in tumor biopsies and blood samples. Methods: The current pilot study (n=15) will assess the hypothesis that Tregs, which are elevated in HNSCC, can be suppressed with cyclophosphamide and that this suppression can lead to improved anti-tumor responses mediated by cetuximab. Eligibility: Metastatic HNSCC progressed on initial chemotherapy or not a candidate for platinum Treatment: Daily oral cyclophosphamide 50 mg bid and weekly cetuximab (SOC). Patients will have blood collected for immune monitoring at weeks 0, 3, 6, 12 and pre and post treatment biopsies at week 0, 6. T cell subsets, NK cell function, Tregs, MDSC will be assessed at tumor site and in blood for immune response. Restaging CT scans will be done pretreatment and at weeks 6, 12. Clinical trial information: NCT01581970.
N-SAS BC06: A phase III study of adjuvant endocrine therapy with or without chemotherapy for postmenopausal breast cancer patients who responded to neoadjuvant letrozole (LET): The New Primary Endocrine-Therapy Origination Study (NEOS).
Authors: Iwata Hiroji , Ohtani Shoichiro , Fujisawa Tomomi , Taira Naruto , Masuda Norikazu , Kashiwaba Masahiro , Yamamoto Yutaka , Toyama Tatsuya , Yamaguchi Takuhiro 
Published: March 2020

TPS654 Background: It is uncertain whether adjuvant chemotherapy is required in the treatment of postmenopausal women with hormone-responsive and intermediate risk breast cancer. The TAILORx and MINDACT trials are ongoing and utilize gene expression profiling in order to answer this question. We have initiated a new study to address this matter by using response to initial neoadjuvant endocrine therapy. The primary aim of this phase III study is to evaluate the necessity of using adjuvant chemotherapy for the treatment of postmenopausal breast cancer patients with node-negative, ER-positive and HER2-negative tumors who responded to neoadjuvant LET. Methods: Inclusion criteria are T1c-T2N0M0, ER-positive by IHC (<10%), HER2-negative, postmenopausal women under 75 years old and written informed consent. Lymph node positive patients as assessed by SLNB are excluded. Neoadjuvant LET is administered for 24-28 weeks before surgery. CR, PR or SD patients are then randomized into two arms receiving either chemotherapy plus LET for 4.5-5 years or LET alone for 4.5-5 years after surgery. If the primary tumor response is defined as PD before surgery, the treatment will be changed at the investigator's discretion (surgery, chemotherapy or other endocrine therapy, but these patients will be followed up). The primary endpoint is disease-free survival (DFS), and secondary endpoints are overall survival (OS), response rate of LET, pathological response, breast conserving surgery rate, DFS/OS by response rate of LET, safety, QOL and cost-effectiveness. This study utilizes a randomized selection design. The objective of this design is to select the arm with the better outcome. We also conduct an additional translational research and central pathological review of ER, PgR, HER2, and Ki67.Patient recruitment commenced in May 2008 and 803 patients were enrolled at the end of 2012. A total of 850 patients will be enrolled at the end of May 2013. This study is supported by Public Health Research Foundation. Clinical trial information: UMIN000001090.
PIKHER2: A phase Ib/II study evaluating safety and efficacy of oral BKM120 in combination with lapatinib in HER2-positive, PI3K-activated, trastuzumab-resistant advanced breast cancer.
Authors: Goncalves Anthony , Isambert Nicolas , Campone Mario , Dieras Veronique , Boher Jean Marie , Boyer-Chamard Agnes , Esterni Benjamin , Provansal Magali , Extra Jean-Marc , Viens Patrice 
Published: March 2020

TPS663 Background: Phosphatidylinositol-3-kinase (PI3K)/AKT/mammalian target of rapamycin (mTOR)-pathway is frequently activated in HER2-positive breast cancer and may play a major role in resistance to trastuzumab. BKM120 is an oral pan-class I PI3K inhibitor with potent and selective activity against wild-type and mutant PI3K p110α. PIKHER2 study will evaluate safety and efficacy of oral, daily lapatinib-BKM120 combination in HER2-positive, trastuzumab-resistant advanced breast cancer (ABC) with activated PI3K/AKT/mTOR pathway. Methods: This open label, single arm, multi-center study includes a phase Ib dose-escalation part and a phase II expansion part at the recommended dose (RP2D). Primary objectives include determination of the maximum-tolerated dose (MTD) of BKM120 in combination with lapatinib in trastumuzab-resistant HER2-positive ABC (phase Ib part) and evaluation of the activity of BKM120-lapatinib combination at RP2D as measured by objective response rate (ORR) in patients with activated PI3K/AKT/mTOR pathway, as defined by PTEN-negative by IHC and/or somatic mutations (exons 9 and 20) of PIK3CA and/or overexpression of phospho-AKT by IHC (phase II part). Secondary objectives include safety and tolerability of the combination, clinical benefit and progression-free survival, pharmacokinetic profiles, biological and pharmacodynamic correlates. Main eligibility criteria are PS ≤ 1, HER2-positive ABC resistant to trastuzumab, documented activated PI3K/AKT/mTOR pathway (phase II part only). A modified CRM using an adaptive Bayesian model guides the dose escalation of both agents with a maximum of 24 patients planned to be enrolled in phase Ib part. Efficacy will be tested according to a standard 2-stage Simon design under the following unacceptable and desirable hypotheses: H0, ORR <= 10% (unacceptable rate) vs. H1, ORR >=30% (desirable rate). A maximum of 35 patients with activated PI3K/AKT/mTOR pathway is planned to be enrolled in phase II part with an interim look after 18 evaluable patients will have been recruited. Clinical trial information: NCT01589861.
NSABP B-43: A phase III clinical trial to compare trastuzumab (T) given concurrently with radiation therapy (RT) to RT alone for women with HER2+ DCIS resected by lumpectomy (Lx).
Authors: Cobleigh Melody A. , Anderson Stewart J. , Julian Thomas B. , Siziopikou Kalliopi P. , Arthur Douglas W. , Rabinovitch Rachel , Zheng Ping , Mamounas Eleftherios P. , Wolmark Norman 
Published: March 2020

TPS666 Background: A significant amount of DCIS is ER-negative and/or overexpresses HER2. This study will test HER2-targeted therapy in DCIS. Among T-treated HER2+ patients (pts) with DCIS treated with a single dose of T, T is found in ductal aspirates and antibody-dependent cell-mediated cytotoxicity activity for HER2 is increased. T boosts the effectiveness of RT in breast cancer xenograft models and cell lines. T given during whole breast irradiation (WBI) may improve results for HER2+ DCIS treated with lumpectomy (Lx). A trial to examine this question will enhance the understanding of breast tumor biology, the prevention of such tumors, and could possibly extend breast-conserving surgery benefits for women with DCIS. Methods: After Lx for pure DCIS, each pt’s DCIS lesion is centrally tested for HER2 using ASCO/CAP guidelines. HER2+ pts are randomly assigned to receive 2 doses of T, 3 weeks apart during WBI or to WBI alone. Women ≥18 yrs with a margin-clear Lx for pure DCIS, with ECOG status 0/1 who are clinically or pathologically node negative are eligible. ER and/or PR status must be known before random assignment. Primary aims are to determine if T decreases ipsilateral breast cancer (IBC) recurrence, ipsilateral skin cancer recurrence, or ipsilateral DCIS. Secondary aims are to determine the benefit of T in preventing regional or distant recurrence and contralateral invasive breast cancer or DCIS. B-43 will determine if DFS, recurrence-free interval, and/or overall survival can be improved with the use of T. 2000 pts will be accrued over 7.9 yrs, with a definitive analysis of primary endpoints performed at163 IBC events (7.5 - 8 yrs after protocol initiation) with an 80% power to detect a hazard reduction of 36%, from 1.73 IBC events per 100 pt-yrs to 1.11 events per 100 pt-yrs. The 36% observed reduction in the hazard of IIBCR-SCR-DCIS on the T arm is based on a projection of 40% hazard reduction if the compliance were perfect, with a 10% noncompliance rate. As of 1-1-13, 1,127 pts have been randomized into the study. Support: PHS NCI-U10-CA-69651, -12027, and -P30-CA-14599 from the US NCI, and Genentech, Inc. Clinical trial information: NCT00769379.
BATTLE-2 program: A biomarker-integrated targeted therapy study in previously treated patients with advanced non-small cell lung cancer (NSCLC).
Authors: Papadimitrakopoulou Vassiliki , Wistuba Ignacio Ivan , Lee J. Jack , Tsao Anne S. , Kalhor Neda , Fossella Frank V. , Heymach John , Alden Christine M , Gettinger Scott N. , Coombes Kevin R. , Saintigny Pierre , Tang Ximing , Duffield Emily , Boyer Julie , Davis Suzanne E , Powis Garth , Mauro David J. , Rubin Eric H. , Hong Waun Ki , Herbst Roy S. 
Published: March 2020

TPS8118 Background: New strategies incorporating a personalized medicine approach for NSCLC treatment are increasingly explored and were pioneered in the prospective, biomarker-driven clinical program titled Biomarker-integrated Approaches of Targeted Therapy for Lung Cancer Elimination (BATTLE-1) (Kim et al Cancer Discov 2011;1:44). Effective therapeutic strategies for mutant KRAS and other biomarkers of resistance in refractory NSCLC remain an unmet medical need. The BATTLE-2 clinical study is using EGFR, PI3K/AKT and MEK inhibitors and is designed to identify biomarkers for optimal patient selection for these therapies, with a long-term goal to significantly improve the survival of NCSLC patients (pts) (ClinicalTrials.gov NCT01248247). Methods: This is a four-arm, open-label, multi-center, biopsy-driven, adaptive randomization, phase II clinical trial in refractory NSCLC pts (failed at least 1 prior line of therapy). After a study-entry tumor biopsy, pts are adaptively randomized, based on KRAS status, to 4 trial arms: erlotinib, erlotinib plus the AKT inhibitor MK-2206, MK-2206 plus the MEK inhibitor selumetinib, and sorafenib. The primary objective is 8-week disease control rate (DCR). Baseline tumor testing includes KRAS and EGFR mutations and EML4/ALK translocation, the latter two being exclusion criteria. The trial is conducted in 2 stages. In Stage 1, 200 evaluable pts are adaptively randomized (AR) based on observed 8-week DCR and KRAS status while predictive biomarkers are being developed. In Stage 2, the AR model is refined to include the most predictive biomarkers tested in Stage 1, with subsequent Stage 2 AR based on the new algorithm, to a total of 400 evaluable pts. Selection of Stage 2 single and/or composite markers (“signatures”) follows a rigorous, internally and externally reviewed statistical analysis. All Stage 1 and 2 randomization biomarker assays are CLIA-certified. 219 pts have been enrolled and 124 pts randomized. 100 pts are evaluable for the 8-week DCR endpoint. Accrual updates, demographics, and further details will be presented at the meeting. Supported by NCI R01CA155196-01A1. Clinical trial information: NCT01248247.
Phase III trial of brentuximab vedotin and CHP versus CHOP in the frontline treatment of patients (pts) with CD30+ mature T-cell lymphomas (MTCL).
Authors: O'Connor Owen A. , Pro Barbara , Illidge Tim , Trumper Lorenz H. , Larsen Emily K. , Kennedy Dana A. 
Published: March 2020

TPS8611 Background: MTCL including systemic anaplastic large cell lymphoma (sALCL) are aggressive neoplasms. Anthracycline-based multiagent chemotherapy regimens have demonstrated response rates ranging from 76 to 88%. Five-year overall survival rates range from 12 to 49% depending on the histologic subtype. Brentuximab vedotin is an antibody drug conjugate that has shown efficacy in a pivotal phase 2 study as a single agent in relapsed sALCL (Pro et al., J Clin Oncol, 2012) and evidence of clinical activity in combination with CHP in the frontline treatment of MTCL including sALCL in a phase 1 study (Fanale et al., ASH 2012). Methods: This randomized, double-blind, placebo-controlled, multicenter, phase 3 study (NCT01777152) is evaluating the safety and efficacy of 1.8 mg/kg brentuximab vedotin with CHP (A+CHP) vs CHOP for frontline treatment of CD30+ MTCL. Pts must have FDG-avid disease by PET and measureable disease of at least 1.5 cm by CT. Approximately 300 pts will be randomized 1:1 to receive A+CHP or CHOP for 6–8 cycles (q3wk). Randomization will be stratified by ALK+ sALCL vs other histologic subtypes and IPI score (0–1, 2–3, or 4–5). The target proportion of pts with a diagnosis of sALCL will be 75%. The primary objective is to compare progression-free survival (PFS) between the 2 treatment arms as determined by an independent review facility (IRF). Secondary objectives include comparisons of PFS per IRF in sALCL patients, safety, overall survival, and complete remission rate between the 2 arms. After completion of treatment, pts will be followed for disease progression, medical resource utilization, quality of life, and survival. Post-treatment stem cell transplant is permitted. Efficacy assessments will use the Revised Response Criteria for Malignant Lymphoma (Cheson 2007). CT and PET scans will be performed at baseline, after Cycle 4, and after the completion of treatment. CT scans will also be performed at regular intervals during follow-up until disease progression, death, or analysis of the primary endpoint. Safety assessments will occur throughout the study until 30 days after last dose of study treatment. Enrollment for this global trial began in early 2013. Clinical trial information: NCT01777152.
A phase III study of ibrutinib in combination with bendamustine and rituximab (BR) in elderly patients with newly diagnosed mantle cell lymphoma (MCL).
Authors: Wang Michael , Gordon Leo I. , Rule Simon , Goy Andre , Hermine Olivier , Rizo Aleksandra , Zhuang Sen Hong , Dreyling Martin H. 
Published: March 2020

TPS8613^ Background: MCL is a distinct subtype of B-cell non-Hodgkin lymphoma (NHL) accounting for approximately 6% of NHL diagnoses. Current immunochemotherapy followed by rituximab maintenance results in a prolonged duration of remission, but a constant relapse pattern is still observed. Ibrutinib, an oral Bruton's tyrosine kinase(BTK) inhibitor, demonstrated promising single-agent activity in 115 patients with relapsed or refractory MCL who were enrolled in the phase II study PCYC-1104. The overall response rate (ORR) was 68%, with 46% of patients achieving partial response (PR) and 22% achieving complete remission (CR) (Wang ASH 2012). Blum et al (ASH 2012) demonstrated that ibrutinib can be safely combined with BR in a phase I combination study in relapsed or refractory NHL and that it enhanced BR’s clinical activity with an ORR in 5 evaluable MCL patients of 100% (80% CR, 20% PR). These data suggest that combining ibrutinib with BR will improve the outcome of these patients. Methods: The SHINE study, PCI-32765MCL3002, is a phase III double-blind study of ibrutinib in combination with BR versus BR for the treatment of patients with newly diagnosed MCL. The study aims to enroll 520 patients (approximately 260 patients per arm). All patients will receive BR therapy for 6 cycles; those patients achieving a CR or PR will receive R maintenance for 2 years. In addition to BR and R, all patients will receive an oral daily dose of 560 mg ibrutinib or placebo concomitant with the chemotherapy and ongoing as a single agent until disease progression or unacceptable toxicity. The primary objective is to evaluate if the addition of ibrutinib to BR will result in prolongation of progression-free survival, with secondary objectives of ORR (CR+PR), CR rate, duration of response, safety, and overall survival. The study will enroll patients aged 65 years or older who are not suitable for high-dose chemotherapy. Key exclusion criteria include diagnosis or treatment for malignancy other than MCL, requirement for treatment with warfarin or equivalent vitamin K antagonists, and treatment with strong CYP3A4/5 inhibitors. Approximately 200 sites globally will enroll patients. Enrollment began in Q1 of 2013. Clinical trial information: NCT01776840.