bluuebunny/crossref_metadata_2025_split huggingface dataset:
Randomized, double-blind, placebo-controlled proof of concept study of tasquinimod maintenance therapy in patients with metastatic castrate-resistant prostate cancer (mCRPC) who experience response or stabilization during first-line docetaxel chemotherapy.
Authors: Fizazi Karim , Heidenreich Axel , Daugaard Gedske , Bellmunt Joaquim , Germann Nathalie , Chetaille Eric 
Published: March 2020

TPS5098^ Background: Docetaxel is the standard first-line chemotherapy for mCRPC. Most patients experience disease response or stabilization on docetaxel, although no treatment is currently used to maintain efficacy when docetaxel is stopped. Tasquinimod is an oral, quinoline-3-carboxamide derivative that binds to S100A9, with immunomodulatory, anti-angiogenic and anti-metastatic activity and a manageable safety profile. Tasquinimod demonstrated significantly improved PFS (7.6 v 3.3 mo) in asymptomatic to mildly symptomatic mCRPC (Pili, R. et al. J Clin Oncol 2011; 29: 4022-8) and is in phase III development. The purpose of this study is to assess whether tasquinimod used as a switch maintenance therapy can postpone cancer progression in patients with mCRPC with response or stabilization on first-line docetaxel therapy. Methods: Design: Phase II, multinational, randomized, double-blind, placebo-controlled proof of concept study. Patients with mCRPC will be randomly assigned (ratio 1:1) to receive tasquinimod or placebo. Randomization will be stratified by presence of visceral metastases and opioid analgesic use for cancer-related pain. Patient population: 140 male patients aged ≥18 years with histologically documented mCRPC and ECOG performance status 0 or 1 will be randomized. Before study entry, patients should have received ≥6 cycles of docetaxel and not experienced cancer progression according to PSA and RECIST criteria. Recruitment is ongoing. Dosage: Patients will receive a starting dose of 0.25 mg/day tasquinimod or placebo, with escalation to 0.5 mg/day and 1 mg/day based on individual safety and tolerability. Primary endpoint: Radiological PFS including skeletal-related events, from randomization to the date of radiological progression or death due to any cause. Secondary endpoints: Overall survival, symptomatic PFS, quality of life, pharmacokinetics, safety, PFS on next-line therapy, time to PSA progression, and changes in biomarkers over time. Clinical trial information: NCT01732549.
A phase II study of trebananib (AMG 386) and abiraterone in metastatic castration resistant prostate cancer.
Authors: Shah Avani Atul , Karzai Fatima , Madan Ravi Amrit , Figg William Douglas , Chau Cindy H. , Gulley James L. , Chun Guinevere , Wright John Joseph , Apolo Andrea Borghese , Parnes Howard L. , Dahut William L. 
Published: March 2020

TPS5102 Background: Preclinical studies support the use of an antiangiogenic approach in the treatment of prostate cancer. Trebananib is a novel peptide-Fc fusion protein that sequesters angiopoeitin 1 and angiopoeitin 2, thereby preventing their interaction with their common receptor Tie2, and inhibiting tumor endothelial cell proliferation and tumor growth. Trebananib is currently in Phase 3 trials for the treatment of ovarian carcinoma and has been shown to have clinical activity in multiple tumor types. Previous studies have demonstrated that in vivo alterations of testosterone levels regulate the expression of vascular endothelial growth factor, fibroblast growth factor, and angiopoietin associated factors. Dual inhibition of the androgen and angiogenic axis represents a novel strategy of combined targeted therapy for patients with metastatic castration-resistant prostate cancer (mCRPC). We hypothesize that the addition of trebananib to CYP17 inhibitor abiraterone and prednisone will increase the median progression free survival (PFS) in chemotherapy-naïve mCRPC. Methods: This phase 2 study will evaluate the treatment effect as measured by progression free survival in patients treated with trebananib plus abiraterone/prednisone relative to abiraterone/prednisone alone. 72 patients with progressive, mCRPC will be randomized 1:1 to either study arm. Trebananib is administered intravenously every week, on days 1, 8, 15 and 22 of each 28-day cycle. Abiraterone acetate is taken once daily with prednisone 5 mg twice daily. We have completed the initial run-in phase of trebananib at 15mg/kg and 30mg/kg. The randomized phase of the study will use the 30 mg/kg dose of trebananib with the standard dose (1000 mg) of abiraterone. The primary end point is radiographic PFS. Secondary end points include overall survival, changes in genetic biomarkers related to the androgen and angiogenesis signaling axis, molecular markers of angiogenesis, circulating tumor cells and androgen receptor signaling status in circulating tumor cells before and after treatment. This combination of angiogenesis inhibition and abiraterone has the potential to improve clinical outcomes in front-line therapy for mCRPC. Clinical trial information: NCT01553188.
Early prediction of efficacy of endocrine therapy in breast cancer (BC): Pilot study and validation with 18F fluoroestradiol (18F-FES) PET/CT.
Authors: Gennari Alessandra , Amadori Dino , Brain Etienne , Cortes Javier , Harbeck Nadia , Puntoni Matteo , Wuerstlein Rachel , Nanni Oriana , Muñoz-Couselo Eva , Paganelli Giovanni , Lopera Sierra Maribel , Matteucci Federica , Piccardo Arnoldo , Bruzzi Paolo 
Published: March 2020

TPS649 Background: Almost 70% of early BC are endocrine responsive, as defined by estrogen receptor (ER) expression; however roughly 30% of ER+ BC patients will relapse despite adjuvant ET. Moreover, 10 to 20% of BC metastases lose ER expression. The upfront administration of ET in ER+ women with MBC is recommended by major guidelines. However, the early identification of endocrine resistance might improve systemic treatment options, sparing unnecessary toxicities and inactive drugs. 18F-FES, an oestradiol analogue labeled with 18F, may allow to test the performance of ERs, by testing their in vivo linkage ability. In MBC, 18F-FES uptake has been proposed to be a better predictor of response to ET than ER expression itself. The aim of the ET-FES study is to validate the predictive value of 18F-FES uptake at PET/CT scan in metastatic ER+ patients. Methods: This is aphase II, multicentric european comparative study of first line ET vs CT in ER+ MBC with low 18F- FES uptake. The primary endpoint is disease control rate (DCR). Correlative studies include: 1. Optimization of 18F-FES production; 2. Association between gene alterations in ESR1/ESR2 genes and 18F- FES uptake; 3. Development of a predictive score of endocrine responsiveness based on 18F-FES SUV value and clinical and biological information. All patients with ER+ MBC candidate to first line ET will receive a 18F-FES CT/PET at baseline, in addition to standard staging. Patients with 18F-FES uptake (SUV) > 2 will receive ET. Patients with 18F-FES SUV < 2 will be randomized to ET until disease progression (control arm) or CT (single agents) until PD. A total of 220 patients with ER+ MBC will be enrolled. Of these, approximately 50% (n=110) will show a 18F-FES SUV < 2 and will be randomized to ET or CT. The study will have 85% power to detect an absolute 20% difference in the DCR between arms after 3 months of therapy, assuming a 5% two-sided alpha level and a 10% drop-out rate. Current status: The ET-FES study was approved for funding by the ist Join TRANSCAN European call. 18F-FES production is currently on final development (GMP), and the clinical protocol is being finalized for EC approval in the different EU countries. Clinical trial information: 2013-000287-29.
A randomized, multicenter, double-blind phase III study of palbociclib (PD-0332991), an oral CDK 4/6 inhibitor, plus letrozole versus placebo plus letrozole for the treatment of postmenopausal women with ER(+), HER2(–) breast cancer who have not received any prior systemic anticancer treatment for advanced disease.
Authors: Finn Richard S. , Dieras Veronique , Gelmon Karen A. , Harbeck Nadia , Jones Stephen E. , Koehler Maria , Martin Miguel , Rugo Hope S. , Im Seock-Ah , Toi Masakazu , Gauthier Eric Roland , Huang Xin , Randolph Sophia , Slamon Dennis J. 
Published: March 2020

TPS652 Background: Palbociclib (PD-0332991) is an orally bioavailable selective inhibitor of CDK4/6 that prevents DNA synthesis by prohibiting progression of the cell cycle from G1 to S phase. In a randomized phase II trial comparing palbociclib (PD-0332991) plus letrozole (P + L) to letrozole (L) in postmenopausal women with ER(+), HER2(–) advanced breast cancer (ABC) who had not received any prior systemic anticancer therapy for their advanced disease, P + L demonstrated significantly longer progression-free survival (PFS) vs L (26.1 vs 7.5 mo; HR = 0.37, P < .001) and was generally well tolerated, with uncomplicated neutropenia as the most frequent adverse event (Finn et al SABCS 2012). Methods: Based on phase II data, a global, randomized, double-blind, phase III clinical trial was designed to demonstrate that P + L provides superior clinical benefit compared with L + placebo in postmenopausal women with ER(+), HER2(–) ABC who have not received any prior systemic therapy for their advanced disease. The study aims to assess whether P + L improves median PFS over L at HR of at least 0.7. Approximately 450 eligible patients with locoregionally recurrent or metastatic, pathologically confirmed ABC who are candidates to receive L as first-line treatment for their advanced disease will be randomized 2:1 to receive either P (125 mg QD 3 wk on, 1 wk off) + L (2.5 mg QD) or L (2.5 mg QD) + placebo. Patients who received anastrozole or letrozole as part of their (neo)adjuvant regimen are eligible if their disease progressed more than 12 months from completion of adjuvant therapy. Tumor tissue is required for participation. Secondary endpoints include overall survival, objective response, duration of response, clinical benefit, safety and tolerability, and patient-reported outcomes of health-related quality of life and disease- or treatment-related symptoms. Clinical trial information: NCT01740427.
BOLERO-6: Phase II study of everolimus plus exemestane versus everolimus or capecitabine monotherapy in HR+, HER2- advanced breast cancer.
Authors: Ejlertsen Bent , Jerusalem Guy Heinrich Maria , Hurvitz Sara A. , De Boer Richard H. , Taran Tanya , Sahmoud Tarek , Burris Howard A. 
Published: March 2020

TPS660 Background: Everolimus (EVE), an orally bioavailable inhibitor of the mammalian target of rapamycin (mTOR), has shown clinical activity as monotherapy and in combination with endocrine therapy (ET) in hormone-receptor–positive (HR+; estrogen and/or progesterone receptors) advanced breast cancer (ABC). In a pivotal phase 3 trial in patients with HR+ ABC progressing on ET, EVE + exemestane (EXE) significantly prolonged median progression-free survival (PFS) vs EXE alone per local (7.8 vs 3.2 months; log-rank P<.0001) or central (11.0 months for EVE+EXE vs 4.1 months for EXE alone; log-rank P<.0001) assessment. Capecitabine, an orally administered fluoropyrimidine carbamate indicated as monotherapy in paclitaxel and/or anthracycline-refractory ABC, has shown clinical benefit in patients with HR+, human epidermal growth factor receptor 2-negative (HER2-) ABC. The BOLERO-6 study in patients with HR+, HER2- ABC progressing on prior anastrozole or letrozole will compare PFS following EVE+EXE combination therapy vs EVE or capecitabine monotherapy. Methods: In this multicenter, open-label, randomized, 3-arm, phase 2 study, 300 patients will be randomized to receive either EVE (10 mg/d) + EXE (25 mg/d) combination therapy, or EVE (10 mg/d) alone, or capecitabine (1,250 mg/m2twice daily for 14 d/3-wk cycle) alone, until disease progression. Patients will be stratified based on the presence of visceral disease. Key eligibility criteria include age ≥18 years, postmenopausal status; histologic or cytologic confirmation of estrogen-receptor–positive, HER2- ABC; radiologic or objective evidence of recurrence or progression on prior aromatase inhibitors; Eastern Cooperative Oncology Group (ECOG) performance status ≤2. The primary endpoint is PFS with EVE+EXE vs EVE, based on local radiologic assessment (Response Evaluation Criteria in Solid Tumors [RECIST] 1.1). The key secondary endpoint is PFS with EVE+EXE vs capecitabine. Other secondary endpoints include overall survival, objective response rate, clinical benefit rate, safety, quality of life, and patient satisfaction with treatment. Enrollment will start in Q1 2013. Estimated study completion in Q1 2015. Clinical trial information: NCT01783444.
Human epidermal growth factor receptor 2 (HER2) suppression with the addition of lapatinib to trastuzumab in HER2-positive metastatic breast cancer (HALT: LPT112515).
Authors: Lin Nancy U. , Danso Michael A. , David Alice K. , Muscato Joseph J. , Rayson Daniel , Houck William A. , Ellis Catherine Elizabeth , DeSilvio Michelle , Garofalo Amanda , Levin Jeremy , Winer Eric P. 
Published: March 2020

TPS664 Background: Evidence supports the concept of dual HER2 blockade as a treatment strategy for HER2+ breast cancer (BC). In patients with prior trastuzumab (T)-treated HER2+ metastatic BC (MBC), treatment with T plus lapatinib (L) was associated with longer progression-free survival (PFS) and overall survival (OS) compared with L alone, and had an acceptable safety and tolerability profile. In patients with stage II/III BC, preoperative treatment with T plus L plus paclitaxel (P) resulted in significantly higher pathologic complete response rates compared with P combined with either agent alone. This study is designed to evaluate whether the addition of L improves PFS among women with HER2+ MBC receiving T as maintenance therapy. Methods: In this open-label, Phase III study, 280 patients will be stratified by line of treatment (first/second) and hormone receptor status (positive/negative), then randomized 1:1 to receive maintenance treatment with either L (1000 mg qd, continuously) in combination with T (6 mg/kg once every 3 weeks [q3w]), or T (6 mg/kg q3w) alone until disease progression, death, discontinuation due to adverse events, or other reasons. The primary endpoint is PFS; secondary endpoints are OS, clinical benefit rate, and safety. Eligible patients are females, aged ≥18 years with HER2+ MBC who have completed 12-24 weeks of first-/second-line treatment with T plus chemotherapy with an objective response or stable disease at chemotherapy discontinuation. Patients with stable brain metastases are eligible if entering the study on second-line treatment. Efficacy endpoints will be analyzed in the intent-to-treat population. A total of 193 PFS events is required to detect a 50% increase in median PFS from 18 weeks (T alone) to 27 weeks (L+T) with an associated hazard ratio of 0.667, an 80% power and a 1-sided type I error of 0.025. One interim analysis is planned for futility when ~97 PFS events (50% of required events) have been observed. Safety endpoints will be analyzed in all randomized patients who receive ≥1 dose of study medication. The trial is currently open for accrual in the United States and Canada. Clinical trial information: NCT00968968.
Randomized, multicenter, open-label, phase III study of the BTK inhibitor ibrutinib versus chlorambucil in patients 65 years or older with treatment-naive CLL/SLL (RESONATE-2, PCYC-1115-CA).
Authors: Burger Jan Andreas , Ghia Paolo , Polliack Aaron , Tam Constantine , Suri Deepali , Clow Fong , Kraljevic Silvija , James Danelle Frances , Kipps Thomas J. 
Published: March 2020

TPS7130 Background: There is an unmet need for safer and more effective therapies for CLL patients who are older/have comorbidites. Ibrutinib, a small molecule inhibitor of BTK, has demonstrated single-agent activity in CLL in the Ph 1b/2 study, PCYC-1102-CA. Treatment-naïve (TN) patients aged >= 65 yrs (n=31) experienced an estimated PFS and OS of 96% at 26 months; ORRs per iwCLL were: 10% CR, 58% PR, and 13% PR with lymphocytosis (Byrd, ASH 2012). AEs were generally Grade 1/2, most commonly diarrhea. Incidence of Grade 3/4 hematologic toxicities was low. These findings support a phase III study of ibrutinib in older patients with treatment-naïve CLL/SLL. Methods: The ongoing study is a randomized, multicenter, open label Ph 3 study comparing safety and efficacy of ibrutinib vs. chlorambucil in TN patients aged >= 65 yrs with CLL/SLL. Approximately 272 patients will be randomized in 1:1 ratio to receive either chlorambucil or ibrutinib, stratified for ECOG PS and Rai stage. Oral chlorambucil will be administered at 0.5 mg/kg on Days 1 and 15 of each 28-day cycle, for up to 12 cycles. Ibrutinib 420 mg q.d. will continue until PD or unacceptable toxicity. Key incl. criteria include age >= 65 yrs, active disease requiring treatment per iwCLL, measurable nodal disease by CT, ECOG performance status 0-2, and adequate organ function (ANC ≥1,000/μL, platelets ≥50,000/μL, creatinine clearance ≥30 mL/min). Key excl. criteria include Richter’s transformation, del(17p13.1) or previous treatment for CLL/SLL. The primary endpoint of the study is PFS, assessed by Independent Review Committee (IRC). Secondary endpoints include ORR, MRD-negative CRs, fatigue by FACIT-F, hematological improvement, safety, and tolerability. Subjects who relapse on PCYC-1115 will be enrolled on PCYC-1116 for long term follow up. Second line therapy is investigator choice; ibrutinib will be made available for patients who experience IRC-confirmed PD ≤12 months of completing chlorambucil therapy, if they meet the treatment criteria. Approximately 85 sites will enroll patients in North America, Europe, Israel, Australia/New Zealand and China. Enrollment began in Q1 2013. Clinical trial information: NCT01722487.
A phase III, randomized, controlled study evaluating the efficacy and safety of idelalisib (GS-1101) in combination with ofatumumab for previously treated chronic lymphocytic leukemia (CLL).
Authors: Flinn Ian , Kimby Eva , Cotter Finbarr E. , Giles Francis J. , Janssens Ann , Pulczynski Elisa Jacobsen , Ysebeart Loic , Pluta Andrzej , Garcia Marco Jose Antonio , Taylor Kerry , Owen Carolyn , Johnson David Michael , Aiello Maria , Dansey Roger D. , Dubowy Ronald L. , Jones Jeffrey Alan 
Published: March 2020

TPS7131 Background: PI3K-delta is critical for activation, proliferation and survival of B cells and plays a role in homing and retention in lymphoid tissues. PI3Kδ signaling is hyperactive in many B-cell malignancies. Idelalisib is a first-in-class, selective, oral inhibitor of PI3Kδ that reduces proliferation, enhances apoptosis, and inhibits homing and retention of malignant B cells in lymphoid tissues (Lannutti et al, 2011). Ofatumumab (O) is an anti-CD20 monoclonal antibody approved for the treatment of pts with CLL refractory to fludarabine and alemtuzumab. Phase 1 studies demonstrated that idelalisib, as monotherapy or combined with O, is highly active in pts with heavily pretreated CLL: pts experienced profound and rapid regression of lymphadenopathy, reductions in disease-associated chemokines, and durable clinical benefit with an acceptable safety profile (Furman et al, 2012). Methods: This study will enroll 210 pts with CLL previously treated with a purine analog and/or bendamustine, with measurable lymphadenopathy who require treatment for CLL and have disease that is not refractory to ofatumumab, and are expected to benefit from a change in therapy because of CLL progression <24 months since completion of their last prior treatment. Pts are randomized in a 2:1 ratio (Arm A:Arm B). In Arm A, pts receive idelalisib at 150 mg BID continuously in combination with 12 infusions of O at 1000 mg over ~24 weeks (weekly x 8 then monthly x 4). In Arm B, pts receive 12 infusions of O at 2,000 mg over ~24 weeks. Stratification factors address IGHV mutational status, del(17p)/p53 mutation status, and refractory vs relapsed disease. The primary study endpoint is PFS. Secondary endpoints include ORR, lymph node response rate, CR rate, and OS. This is an event-driven trial and primary endpoint evaluation will be based on independent central review. For the primary efficacy analysis, the difference in PFS between the treatment arms will be assessed in the ITT analysis set using Kaplan-Meier methods and the stratified log-rank test. The study opened for enrollment in Dec 2012. Clinical trial information: NCT01659021.
CA184-156: Randomized, multicenter, double-blind, phase III trial comparing the efficacy of ipilimumab (Ipi) plus etoposide/platinum (EP) versus placebo plus EP in patients (Pts) with newly diagnosed extensive-stage disease small cell lung cancer (ED-SCLC).
Authors: Von Pawel Joachim , Kim Sang-We , Spigel David R. , Zielinski Christoph , Pietanza Maria Catherine , de Pril Veerle , Ballas Marc S. , Reck Martin 
Published: March 2020

TPS7608 Background: Phase III studies have not reported improvement for ED-SCLC beyond EP. Moreover, chemotherapeutic response in SCLC is short-lived, with a median survival of 8–12 months and 5-year survival rates ranging from 1%–2%. Ipi, a fully human monoclonal antibody which binds CTLA-4, augments antitumor immune responses and may potentially improve the clinical benefit of EP. A randomized phase II study of Ipi + paclitaxel/carboplatin (PC) in pts with ED-SCLC showed significant improvement in progression-free survival (PFS) [measured by immune-related response criteria (irRC)] over PC in pts receiving phased Ipi + PC; irRC were derived from WHO criteria to better capture response patterns observed with Ipi. Addition of Ipi trended toward prolonged overall survival (OS) and did not exacerbate PC toxicity; immune-related adverse events were managed using protocol-specific guidelines. This global (~227 sites among 34 countries), multicenter phase III study in pts with ED-SCLC (ClinicalTrials.gov identifier NCT01450761) will determine if adding Ipi to EP increases OS vs EP alone. Methods: Pts with first-line ED-SCLC and ECOG 0-1 will be eligible; pts with a history of autoimmune disease will be ineligible. Pts will be randomized (1:1 to either Arm A or Arm B) to 2 cycles of EP (etoposide [100 mg/m2, IV on Days 1-3 Q3W] and cisplatin [75 mg/m2, IV] or carboplatin [AUC=5, IV] once Q3W), followed by 4 cycles of blinded study drug (Ipi 10 mg/kg, IV in Arm A or placebo in Arm B, Q3W) with 2 concurrent cycles (during cycles 3-4) of EP and Ipi (6 cycles of total therapy). Eligible pts will receive Ipi maintenance therapy Q12W until disease progression or unacceptable toxicity; pts with a complete response will also be eligible for prophylactic cranial irradiation at investigator’s discretion. The primary endpoint is OS; secondary endpoints include OS among pts who receive blinded therapy, immune-related and mWHO PFS, best overall response rate, and duration of response. The trial will also characterize safety, and is estimated to enroll 1100 pts. Clinical trial information: NCT01450761.