bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract OT1-1-05: A Phase I pharmacokinetics trial comparing PF-05280014 and trastuzumab in healthy volunteers (REFLECTIONS B327-01)
Authors: Ricart AD , Zacharchuk C , Reich SD , Meng X , Barker KB , Taylor CT , Hansson AG 
Published: August 2014

Abstract
Background: Trastuzumab is a humanized recombinant monoclonal antibody that selectively binds the extracellular domain of human epidermal growth factor receptor 2 (HER2) and is approved for treatment of breast and gastric cancers. PF05280014 is being developed as a potential biosimilar to trastuzumab. In nonclinical evaluations, PF-05280014 has an identical amino acid sequence to trastuzumab and similar physicochemical and in vitro functional properties. The goal of this phase I trial is to demonstrate the pharmacokinetic similarity of PF-05280014 to trastuzumab sourced from both the United States (trastuzumab-US) and European Union (trastuzumab-EU).
Trial design: In this double-blind, parallel group, single dose trial, subjects will be randomized 1:1:1 into 3 arms: PF-05280014; trastuzumab-US, and trastuzumab-EU (NCT01603264).
Eligibility: Healthy male volunteers, 18–55 years of age with normal left ventricular ejection fraction are eligible. Multiple exclusion criteria common to Phase 1 trials are in effect. All subjects must provide informed consent.
Aims: The primary objectives are to demonstrate the pharmacokinetic similarity of PF-05280014 to trastuzumab-US and trastuzumab-EU. Secondary objectives include evaluating the safety, tolerability, and immunogenicity of PF-05280014 compared with US-licensed and EU-approved trastuzumab products.
Statistical methods: Pharmacokinetic similarity will be demonstrated if the 90% confidence interval of the ratio of the area under the concentration-versus-time curve from time 0 to the last time point with quantifiable concentration (AUCT) and maximum concentration (Cmax) of PF-05280014 to both trastuzumab-US and trastuzumab-EU are within 80%–125%. At least 93 subjects, 31/arm, will be needed to provide &gt;81% power to demonstrate pharmacokinetic similarity for all comparisons. The planned enrolment is 105 subjects to account for subjects who may not complete the full follow-up period. The intent-to-treat (ITT) population is defined as all subjects who are randomized to receive treatment. The modified ITT population is defined as all subjects who are randomized and receive at least one dose of treatment and will be used to assess safety, tolerability, and immunogenicity. The per-protocol population is defined as all subjects who are randomized to and receive treatment and do not have any major protocol violations and will be used for the primary evaluation of pharmacokinetic parameters.
Accrual: The target accrual is 105 subjects; present accrual is 17subjects.
Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr OT1-1-05.
Abstract OT2-2-03: Dovitinib (TKI258) or placebo in combination with fulvestrant in postmenopausal, endocrine-resistant HER2–/HR+ breast cancer: a phase II study
Authors: Andre F , Greil R , Denduluri N , Barrios C , Campone M , Cortes J , Neven P , Reddick C , Squires M , Zhang Y , Yovine A , Blackwell K 
Published: August 2014

Abstract
Background: Overcoming endocrine resistance is a critical goal in the treatment of hormone receptor-positive (HR+) breast cancer. Molecular mechanisms associated with endocrine resistance include adaptive cross-talk between the estrogen receptor and the fibroblast growth factor receptor (FGFR). Up to 8% of HR+/ human epidermal growth factor receptor 2 negative (HER2–) breast cancer patients have amplification of the FGFR1 gene, which is associated with resistance to endocrine therapy. In preclinical models, resistance to endocrine therapy can be overcome via FGFR1 inhibition. Dovitinib is a potent oral inhibitor of receptor tyrosine kinases, including FGFR, vascular endothelial growth factor receptor (VEGFR), and platelet derived growth factor receptor (PDGFR), that demonstrated antitumor activity in heavily pretreated breast cancer patients with FGF-pathway amplification (FGFR1, FGFR2, or ligand FGF3; Andre et al, ASCO 2011). Dovitinib may reverse resistance to endocrine therapy related to FGF-pathway amplification and may also inhibit angiogenesis, which plays an essential role in breast cancer development. Dovitinib is studied here in combination with fulvestrant to determine if it can improve outcomes in postmenopausal patients with endocrine resistant HER2−/HR+ breast cancer.
Methods: This is a multicenter, randomized, double-blind, placebo-controlled, phase II trial that will enroll postmenopausal HER2–/HR+ locally advanced or metastatic breast cancer patients (N ≈ 150) progressing within 12 months of completion of adjuvant endocrine therapy or after ≤ 1 prior endocrine therapy in the advanced setting. Patients prospectively undergo molecular screening to enrich for FGF amplification (FGFR1, FGFR2, or FGF3 amplification by qualitative polymerase chain reaction (qPCR); 45 amplified and 30 nonamplified patients per arm). Patients are randomized 1:1 (stratified by FGF-amplification and presence of visceral disease) to receive fulvestrant intramuscularly (500 mg q4w [with an additional dose 2 weeks after the initial dose]) in combination with oral dovitinib (500 mg, 5 days on/2 days off) or placebo until disease progression, unacceptable toxicity, death or discontinuation due to any reason (eg, withdrawal). Crossover is not permitted. The primary endpoint is progression-free survival, with tumor assessments performed q8w. Secondary endpoints include overall response rate per RECIST v1.1, duration of response, overall survival, Eastern Cooperative Oncology Group performance status and patient-reported outcome scores over time, and safety. Additionally, the pharmacodynamic effect of dovitinib on FGFR-associated angiogenic pathways in tumor specimens and potential predictive biomarkers of response to dovitinib will be explored.
Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr OT2-2-03.
Abstract OT2-3-03:

D

enosumab versus placebo as adjuvant treatment for women with early-stage breast

ca

ncer at high risk of disease

re

currence (D-CARE): An international, randomized, double-blind, placebo-controlled phase 3 clinical trial
Authors: Goss PE , Barrios CH , Chan A , Finkelstein DM , Iwata H , Martin M , Braun A , Ke C , Maniar T , Coleman RE 
Published: August 2014

Abstract
Bone represents approximately 40% of all first recurrences in women with early-stage breast cancer and is a common site of distant recurrence. In preclinical studies, RANKL inhibition significantly delays skeletal tumor formation, reduces skeletal tumor burden, and prolongs survival of tumor-bearing mice. Denosumab is approved for the prevention of skeletal-related events (SREs) in patients with established bone metastases from solid tumors.
Purpose: The D-CARE trial is designed to assess if denosumab treatment prolongs bone metastasis-free survival (BMFS) and disease-free survival (DFS) in the adjuvant breast cancer setting. The primary endpoint of this event-driven trial is BMFS. Secondary endpoints include DFS and overall survival. Additional endpoints are safety, breast density, incidence of SREs (following the development of bone metastasis) patient reported outcomes, and biomarkers.
Methods: In this international, randomized, double-blind, and placebo controlled phase 3 trial, approximately 4,500 women with stage II or III breast cancer, at high risk for recurrence and with known hormone and HER-2 receptor status, are eligible. High risk is defined as biopsy evidence of breast cancer in regional lymph nodes, tumor size &gt; 5 cm, (T3), or locally advanced disease (T4). Standard-of-care adjuvant or neoadjuvant chemo-, endocrine, or HER-2 targeted therapy, alone or in combination, must be planned. Patients with a prior history of breast cancer (except ductal carcinoma in situ or lobular carcinoma in situ) or distant metastasis, oral bisphosphonate (BP) use within 1 year of randomization, or any intravenous BP use, are not eligible. Patients are randomized 1:1 to receive denosumab 120 mg or placebo subcutaneously monthly for 6 months, then every 3 months for a total of 5 years of treatment. Supplemental vitamin D (≥ 400 IU) and calcium (≥ 500 mg) will be administered. The trial, sponsored by Amgen Inc. and registered with the ClinicalTrials.gov identifier NCT01077154, began enrolling patients in June 2010 and is expected to complete enrollment in late 2012.
Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr OT2-3-03.
Abstract OT2-3-07: A randomized, phase 2 study of the poly (ADP-ribose) polymerase (PARP) inhibitor veliparib (ABT-888) in combination with temozolomide (TMZ) or in combination with carboplatin (C) and paclitaxel (P) versus placebo plus C/P in subjects with BRCA1 or BRACA2 mutation and metastatic breast cancer
Authors: Isakoff SJ , Pulhalla S , Shepherd SP , Falotico N , Kaufman B , Friedlander M , Robson M , Domchek S , Garber J , McKeegan E , Chyla B , Qian J , Giranda VL 
Published: August 2014

Abstract
Background: Veliparib is a potent, oral PARP inhibitor that inhibits DNA repair, primarily through single strand break repair. BRCA1/2 mutated tumors are defective in homologous recombination, leading to more error prone mechanisms of DNA repair and increased sensitivity to PARP inhibition. Veliparib and TMZ recently demonstrated promising activity in BRCA1/2 mutation carriers, and veliparib and C/P is being evaluated in a CTEP Phase 1 study. This Phase 2 multinational study will evaluate veliparib in combination with TMZ and in combination with C/P compared to an active, placebo-controlled arm of C/P in subjects with BRCA1 or BRCA2 mutation and metastatic breast cancer.
Methods: Approximately 240 subjects will be randomized in a 1:1:1 ratio to: 1) Veliparib 40 mg BID D1-7 + TMZ (150–200 mg/m2 QD D1-5) of every 28 day cycle; or 2) Veliparib 120 mg BID D1-7 + C (AUC 6, D3) and P (175 mg/m2, D3) of every 21 day cycle or 3) placebo BID D1-7 + C/P. Key eligibility includes known deleterious BRCA1/2 mutation, ≤1 prior chemotherapy for metastatic disease, and no prior platinum agent. Randomization will be stratified by hormone receptor positive versus negative, prior vs. no prior cytotoxic therapy, and ECOG 0–1 vs 2.
The primary objective is progression-free survival (PFS) using RECIST 1.1. Secondary objectives include overall survival, objective response rate, duration of response and safety/tolerability. Optional paired tissue biopsies will be obtained at baseline and at progression to evaluate markers of response and resistance. Additional correlatives for response include assessment of peripheral blood, CTCs, and archived tissue for markers of disease status, gene methylation and mutational status, and tumor-specific alteration of cellular proteins/peptides and/or nucleic acids. Using the log-rank test for PFS, with 150 PFS events the study will have ≥ 80% power at 2-sided α level of 0.05 to detect a statistically significant treatment effect assuming a true hazard ratio of 0.58 favoring the 2 treatment groups containing veliparib. As of June 11, 2012, 5 subjects have been enrolled.
Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr OT2-3-07.
Abstract OT3-2-02: The PREDICT Study (Prospective, Randomized Early Detection and Intervention after Breast Cancer-Treatment, for women at risk of lymphedema)
Authors: Taghian AG , Skolny MN , O'Toole J , Miller CL , Jammallo LS , Specht MC 
Published: August 2014

Abstract
Introduction: It is well-documented that lymphedema is one of the most feared long-term side effects of breast cancer (BC) treatment. However, to date, a standardized approach for the quantification and treatment of breast cancer-related lymphedema (BCRL) has yet to be established.
Aims: We propose a screening and intervention trial that will assess the efficacy of early detection and intervention for BCRL. Intervention comprises the use of compression garments for mild lymphedema and compression garments +/− nighttime bandaging for moderate lymphedema. Other factors to be evaluated include: symptom clusters, treatment adherence, fear avoidance behavior, quality of life (QOL), upper extremity function, and risk factors for BCRL.
Eligibility Criteria: Women 18 years + with a confirmed BC diagnosis, no history of BC, no known metastatic or locally advanced disease, no history of primary lymphedema, sentinel lymph node biopsy or axillary lymph node dissection as part of definitive breast surgery.
Study Design: A two-stage study which includes a Screening and an Intervention trial. The screening arm will evaluate arm volume change during and after BC treatment with target accrual of 8000. Patients will undergo measurements via perometry and complete the MGH Lymphedema Evaluation Following Treatment for Breast Cancer (LEFT-BC) Survey at each screening appointment to evaluate changes in functionality, upper extremity utilization (fear associated avoidance), and QOL. Screening visits will occur pre- and post - operatively, at the conclusion of chemotherapy and radiation therapy and every 3–7 months thereafter. Patients will become eligible for enrollment into the intervention trial if, during the course of screening, they develop a relative arm volume change (RVC) of ≥ 5% which persists at a verification measurement within 4–8 weeks. Eligible subjects are enrolled into one of two groups based on verification RVC: Group I – Mild Lymphedema (5–10% RVC) or Group II – Moderate Lymphedema (11–20% RVC). Subjects are then randomized within each group. Group I subjects are randomized to one of two arms: I-A – Observation, I-B – Compression, and Group II subjects are randomized to one of two arms: II-A – Compression, II-B – Compression + Night Compression Bandaging. Target accrual for the intervention trial is 336 subjects (Group I: 208, Group II: 128).
Clinical Relevance: The results of this study will yield level I evidence on the effectiveness of early detection and intervention for BCRL. Findings may shape clinical practice in diagnosis and treatment, as well as provide insight regarding the risk factors, symptoms, upper extremity function, and quality of life (QOL) associated with BCRL.
*Funding by awards R01CA139118 & 3P5OCA089393, AGT
Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr OT3-2-02.
Abstract OT3-3-03: Silent risk? Cardiovascular risk factors in survivors of breast cancer treated with anthracyclines.
Authors: Murtagh Gillian , Lyons Tomas G , Geraghty Lucy , Conlon Carmel , Tallon Elaine M , Ballot Jo , Patel Anil , Badabhagni Mallikarjuna , Ledwidge Mark T , Fennelly David , Gullo Giuseppe , Walshe Janice , Crown John , McDonald Kenneth M 
Published: August 2014

Abstract
Withdrawn by Author
Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr OT3-3-03.
Abstract OT3-3-09: ARTemis trial - randomised trial with neo-adjuvant chemotherapy for patients with early breast cancer
Authors: Earl HM , Blenkinsop C , Grybowicz L , Vallier A-L , Cameron DA , Bartlett JMS , Murray N , Caldas C , Thomas J , Dunn JA , Higgins HB , Hiller L , Hayward L 
Published: August 2014

Abstract
Background: Bevacizumab, a humanised monoclonal antibody which targets vascular endothelial growth factor (VEGF), has shown promising anti-tumour effect when given concurrently with taxane-based chemotherapy in breast cancer. However two neoadjuvant breast cancer trials have produced conflicting results. The GEPARQUINTO trial reported significant benefit only in the triple negative patients (pCR 27.8% vs 36.4% p = 0.021). The NSABP-B40 study showed significant benefit for bevacizumab only in the ER+ve patients (pathological complete response (pCR) in ER+ve population 15.2% vs 23.3%, p = 0.008).
Trial design: ARTemis is a phase III randomised trial to determine whether the addition to neo-adjuvant chemotherapy of bevacizumab is more effective than standard chemotherapy alone in patients with HER2-negative early breast cancer. A total of 400 patients will be randomised into each of the two treatment arms which will allow an absolute difference in the pCR rates in excess of 10% to be detected at the 5% (2-sided) level of significance with an 85% power. Primary outcome is pathological complete response rates after neo-adjuvant chemotherapy, i.e. no residual invasive carcinoma in the breast, and no evidence of metastatic disease within the lymph nodes. Secondary outcomes are disease free survival, overall survival, complete pathological response rates in breast alone, radiological response after 3 and 6 cycles of chemotherapy and rate of breast conservation and toxicities. Translational work (ARTemis-Science): collection of blood samples, and paraffin-embedded formalin-fixed and fresh tissue samples to investigate whether markers for chemotherapy response/resistance, and pharmacogenetic and pharmacogenomic markers can be correlated with outcomes (pathCR and RFS) in patients randomised to receive bevacizumab versus those that do not.
Eligibility criteria: Histologically confirmed HER2-negative invasive breast cancer; T2 to T4 tumour and/or large/fixed axillary nodes (&gt;20mm/clinical N2 or N3), or inflammatory disease; suitable for, and fit to receive neo-adjuvant chemotherapy and an anti-angiogenic.
Results: Recruitment into ARTemis began in April 2009 and as of June 2012 had recruited 600 (75%) patients and 65 sites are open for recruitment. ARTemis is due to complete recruitment by first quarter of 2013 and the first planned interim analysis of the primary outcome will be December 2013.
Conclusion: The IDSMC reviewed the trial in June 2012 and recommended continuation of recruitment to this important trial given there were no safety concerns.
Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr OT3-3-09.
Abstract OT3-4-05: Use of early CIRculating tumor CElls count changes to guide the use of chemotherapy in advanced metastatic breast cancer patients: the CirCe01 randomized trial
Authors: Bidard F-C , Asselain B , Baffert S , Brain E , Campone M , Delaloge S , Bachelot T , Tubiana-Mathieu N , Pelissier S , Pierga J-Y 
Published: August 2014

Abstract
Background: After the SWOG0500 trial, the CirCe01 trial (NCT01349842) is the second randomized attempt to demonstrate that patients who received a first cycle of chemotherapy and whose CTC count did not drop should be switched off this chemotherapy.
The clinical setting used here is a population with high chemoresistance prevalence, i.e. patients starting a third line chemotherapy; the CTC test will be also repeated at the beginning of every new chemotherapy line in patients randomized in the CTC arm (i.e. to evaluate the 3rd, 4th, 5th … lines).
In the CTC arm, it has been hypothesized that many patients with chemoresistant tumor will experience repeated early chemotherapy changes (e.g. 3 chemotherapy regimens tested in 9 weeks), giving support to the discontinuation of inefficient, toxic and costly chemotherapies and the start of palliative care. It is believed, for this subgroup of patients, that such de-escalating management will benefit both patients and healthcare systems. For some other patients, it is also expected that they will benefit from the early chemotherapy turn-around and find earlier an efficient therapy among all those tested.
Methods: The main inclusion criteria are metastatic breast cancer patients starting a third line of chemotherapy and an elevated CTC count at baseline.
304 metastatic breast cancer patients will be randomized between the standard arm, in which the treatment management is made following the current standard of care, and the CTC-driven arm, in which the “response” after every first cycle of any new chemotherapy line is assessed by CTC count made before the second cycle. Chemotherapies which did not lead to a significant reduction of CTC count are discontinued, and the patient might be offered another chemotherapy regimen (which will be also evaluated by CTC).
The medical primary endpoint of the trial is the overall survival, whereas a medico-economic study as a co-primary endpoint. Several secondary endpoints are pre-planned, including progression-free survival, quality of life, anxiety/depression and comparison with serum markers.
Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr OT3-4-05.
Abstract OT3-4-06: Circulating tumor cells to guide the choice between chemotherapy and hormone therapy as first line treatment for hormone receptors positive metastatic breast cancer patients: the STIC CTC METABREAST trial
Authors: Bidard F-C , Baffert S , Hajage D , Brain E , Armanet S , Simondi C , Mignot L , Asselain B , Tresca P , Pierga J-Y 
Published: August 2014

Abstract
Background: Baseline CTC count already demonstrated its accuracy as an independent prognostic marker in metastatic breast cancer (MBC), before the start of any treatment (Cristofanilli, NEJM 2004; Pierga Ann Oncol 2011) for progression free survival and overall survival. Multivariate analyses performed in both a pooled analysis (Liu, ASCO 2011) and in the IC 2006–04 study showed that the other independent prognostic factors were the performance status and hormone-receptor (HR) status. Oppositely, the other criteria that are frequently used to choose between hormone therapy and chemotherapy for the treatment of first line hormone receptor-positive MBC patients (e.g. number of metastatic sites, visceral disease, metastasis-free interval…) were not independent prognostic factors. As CTC count is highly correlated to PFS, we designed a large pivotal phase III trial to evaluate the use of CTC to determine the disease aggressiveness and the choice of first line treatment in potentially hormonosensitive MBC.
Trial design: First line metastatic breast cancer patients will be randomized between the clinician choice and CTC count-driven choice. In the CTC arm, patients with ≥5 CTC/7.5ml will receive chemotherapy whereas patients with &lt;5 CTC/7.5ml will receive endocrine therapy as first line treatment.
Eligibility criteria: Main inclusion criteria include hormone receptor-positive metastatic breast cancer patients with no previous treatment for the metastatic disease, and who can receive either hormone therapy or chemotherapy as first line treatment.
Statistical methods: As every patient will receive a treatment, this pivotal trial has been designed to show a non-inferiority of the CTC arm for PFS (primary clinical endpoint) and a superiority of the CTC arm for the medico-economics study (co-primary endpoint).
Present accrual and target accrual: This trial began in March 2012 and more than 15 French cancer centers participate to this study. The accrual of 996 metastatic breast cancer patients should be completed in 2 to 3 years. 20 patients have been included in 2 months in the first opened center.
Contact information for people with a specific interest in the trial
The STIC CTC METABREAST trial has been funded by the French Ministry of Health (STIC program) and Veridex. The promoter is the Institut Curie (Paris).
Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr OT3-4-06.
Abstract P1-01-02: Axillary Reverse Mapping: A Prospective Study on Feasibility, Oncologic Safety, and Lymphedema Prevention.
Authors: Connor Carol S , McGinness Marilee K , Mammen Joshua MV , Ranallo Lori B , LaFaver Stephanie M , Klemp Jennifer R , Fan Fang , Mahnken Jonathan D 
Published: August 2014

Abstract
Withdrawn by Author
Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P1-01-02.