bluuebunny/crossref_metadata_2025_split huggingface dataset:
OT1-02-02: HALT MBC: HER2 Suppression with the Addition of Lapatinib to Trastuzumab in HER2−Positive Metastatic Breast Cancer (LPT112515).
Authors: Lin N , Danso M , David A , Muscato J , Ellis C , DeSilvio M , Garofalo A , Nagarwala Y , Winer E 
Published: June 2012

Abstract
Background Lapatinib in combination with trastuzumab enhanced anti-tumor activity in HER2−positive breast cancer (BC) preclinical models. In patients (pts) with trastuzumab-treated, HER2−positive metastatic (M) BC, treatment with the combination was associated with longer progression-free (PFS) and overall survival (OS) compared with lapatinib alone. In pts with stage II/III BC, preoperative treatment with the combination plus paclitaxel resulted in significantly higher pathological complete response rates compared with paclitaxel combined with either agent alone. This evidence supports the concept of dual HER2 blockade as a treatment strategy for HER2−positive BC. This present study is designed to evaluate whether the addition of lapatinib improves PFS among women with HER2−positive MBC receiving trastuzumab as maintenance therapy.
Trial Design In this open-label, Phase III study, pts are stratified by line of treatment (first/second) and hormone receptor status (positive/negative) then randomized 1:1 to receive maintenance treatment with either lapatinib (1000mg once daily, continuously) in combination with trastuzumab (6mg/kg once every 3 weeks [Q3W]) or trastuzumab (6mg/kg Q3W) alone. Pts will receive study treatment until disease progression, death, discontinuation due to adverse events or other reasons.
Eligibility Criteria Pts with HER2−positive MBC who have completed 12–24 weeks of first- or second-line treatment with trastuzumab plus chemotherapy and have objective response or stable disease. Pts with stable brain metastasis are eligible if entering the study on second-line treatment.
Specific Aims The primary objective is to compare PFS of lapatinib in combination with trastuzumab to trastuzumab as continued HER2 suppression therapy. Secondary objectives are to evaluate OS, clinical benefit rate, safety and tolerability.
Statistical Methods Efficacy endpoints will be analyzed in the intent to treat population. A total of 193 PFS events from 280 randomized pts will be required to detect a 50% increase in median PFS in pts who receive lapatinib plus trastuzumab compared with trastuzumab (median PFS time is 27 versus 18 weeks, respectively); hazard ratio of 0.67 with an 80% power and a 1-sided type I error of 0.025.
Present and Target Accrual Sixteen of the target 280 pts have been randomized. The trial is currently open for accrual in the United States and Canada.
Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr OT1-02-02.
OT1-02-03: EGF114299: Safety and Efficacy of an Aromatase Inhibitor (AI) in Combination with Lapatinib (L), Trastuzumab (T) or Both for the Treatment of Hormone Receptor-Positive (HR+), HER2+ Metastatic Breast Cancer (MBC).
Authors: Johnston S , Leigh M , Florance A , Wroblewski S , Gradishar W 
Published: June 2012

Abstract
Background: Data from the L plus letrozole (EGF30008) and the Trastuzumab and Anastrozole Directed Against ER-Positive HER2−Positive Mammary Carcinoma (TaNDEM) studies demonstrated that HER2 targeted and endocrine therapy (ET) is a better strategy than ET alone. In EGF30008, progression-free survival (PFS) in the HER2+ population was statistically significantly longer in the letrozole plus L group compared with the letrozole plus placebo group. The HR was 0.71 (95% CI: 0.53−0.96; stratified log rank P=.019). Median PFS was 35.4 weeks in the letrozole plus L group compared with 13.0 weeks in the letrozole plus placebo group.
The present study (EGF114299) is a phase III, open-label, multicenter trial designed to evaluate benefit in overall survival (OS) provided by L/T/AI and L/AI, in pts with HR+/HER2+ MBC who have received neo-/adjuvant T and ET. It will also provide further data on dual HER2 suppression in an attempt to prevent acquired endocrine resistance.
Trial Design: Pts will be randomized to 1 of 3 treatment arms: L 1000 mg po QD plus T (loading dose of 8 mg/kg followed by maintenance with 6 mg/kg IV q3w plus an AI po QD); T plus an AI; or L 1500 mg po QD plus an AI). Choices of AI include letrozole, anastrozole, or exemestane.
Eligibility Criteria: HR+ (ER and/or PgR) and HER2+ Stage IV MBC pts are to be enrolled. Pts must have received neo-/adjuvant T and ET, and are treatment naive for MBC.
Specific Aims: The primary objective is to evaluate OS of L/T/AI as compared with T/AI. The secondary objectives are to assess: OS in T/AI vs L/AI and T/L/AI vs L/AI; PFS; overall response rate; clinical benefit rate; safety and tolerability; and QoL relative to baseline. A 4-year recruitment is anticipated. More than 200 centers across 25 countries are planned; approximately 50 centers are currently open for enrollment.
Statistical Methods: The study is powered to detect a 42% improvement in the risk of death (HR=0.70) in all pts receiving L/T/AI (median 28.5 months) compared with T/AI (median 20 months). The hypothesis will be tested using a 1-sided test for superiority with a=0.025 with a power of 80%.
Present and Target Accrual: One (1) of 525 pts has been randomized. The majority of eligible pts may reside in countries where T is commercially available and reimbursable, particularly North America and Western Europe. Patients who have participated in previous neo-/adjuvant trials including a T regimen are eligible, provided they meet all other inclusion criteria.
The study is currently recruiting pts, with an anticipated target accrual of 525 patients by March 2016.
Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr OT1-02-03.
OT2-03-02: Prospective Neo-Adjuvant Registry Trial Linking MammaPrint, Subtyping and Treatment Response: Neoadjuvant Breast Registry – Symphony Trial (NBRST).
Authors: Whitworth P , Beitsch P , Gittleman M , Akbari S 
Published: June 2012

Abstract
Background MammaPrint is performed on a diagnostic multi-gene array featuring &gt;4,500 genes. This platform enables additional gene expression profiles to be analyzed simultaneously on one tumor specimen. BluePrint, an eighty gene Molecular Subtyping Profile, discriminates between three distinctive subtypes; Basal-type, Luminal-type, and ERBB2 (HER2)-type. Studies have shown marked differences in response to neo-adjuvant treatment in groups stratified by MammaPrint and BluePrint.
Trial design A prospective observational, case-only study linking MammaPrint, BluePrint, TargetPrint, TheraPrint (together referred to as the Symphony suite) and possible additional profiles of interest to neoadjuvant treatment response and Distant Metastases Free Survival (DMFS) and Relapse Free Survival (RFS).
20-30 institutions in the US will be invited to contribute clinical patient data from enrolled patients after a MammaPrint, TargetPrint, BluePrint and TheraPrint (Symphony suite) has been successfully performed and the patient has started neo-adjuvant therapy. Treatment is at the discretion of the physician, adhering to NCCN approved regimens or a recognized alternative.
Eligibility criteria
Women with histologically proven breast cancer, who have started or are scheduled to start neo-adjuvant chemotherapy therapy or neo-adjuvant hormone therapy, after successful Symphony suite assessment Age 18–90 Written informed consent No excisional biopsy or axillary dissection No confirmed distant metastatic disease No prior therapy for the treatment of breast cancer
Scope
The scope of this registry study is to measure chemosensitivity as defined by pCR (primary endpoint), or endocrine sensitivity as defined by partial response, (a primary endpoint for neo-adjuvant endocrine therapy and a secondary endpoint for neoadjuvant chemotherapy), metastasis-free survival and relapse-free survival (secondary endpoints) in molecular subgroups, determined by the MammaPrint and BluePrint; as well as correlation to Targetprint and Theraprint read outs in addition to investigating novel response profiles.
Statistical methods
The response rate and corresponding confidence intervals will be presented as a proportion of all patients enrolled. The confidence intervals will be calculated using the normal approximation to the binomial distribution. Comparison of response rates between different molecular subgroups will be conducted using Pearson Chi-square test. Correlation of chemosensitivity and endocrine sensitivity (as defined by pCR) to TheraPrint will be determined using Pearson correlation and linear fit models.
Kaplan-Meier curves for RFS and DMFS will be calculated for different molecular subgroups.
Present accrual and target accrual
The target accrual is to enroll approximately 500 patients in 4 years.
Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr OT2-03-02.
OT2-04-03: Uptake of a Randomized Breast Cancer Prevention Trial Comparing Letrozole to Placebo in BRCA1/2 Mutations Carriers: The FNCLCC ONCO-03/LIBER Trial.
Authors: Pujol P , Lasset C , Berthet P , Dugast C , Delaloge S , Fricker JP , Chabbert Buffet N , Lemonnier J , Roca L , Mijonnet S , Baudry K , Martin AL 
Published: June 2012

Abstract
Background: Women with germline BRCA1or BRCA2 (BRCA1/2) mutations are an extreme risk population for developing breast cancer, with a life-time risk of 56–80%. Prophylactic mastectomy provides a valid option to reduce such risk, but it considerably affects the quality of life. Medical prevention by aromatase inhibitor that has been recently shown to have preventive effect may thus be an alternative. LIBER is an ongoing, double-blind, randomized phase III trial to evaluate the efficacy of five-years letrozole versus placebo to decrease breast cancer incidence in post-menopausal BRCA1/2 mutation carriers (NCT00673335). We present data on the uptake of this trial. Methods: To evaluate theoretical feasibility, we compared inclusion criteria of women in the LIBER trial (n=113) to characteristics of women entered in the prospective ongoing national GENEPSO cohort (n=1505). Uptake was evaluated through a survey sent to all active centres, with responses obtained from 17 of the 20 (85%) centres. Results: According to characteristics of the women included in GENEPSO cohort (n=1505) and the survey, approximately one third of BRCA1/2 mutation carriers are eligible for this study. From november 2009 to may 2010, 534 women eligible from chart review have been informed by mail of the trial and were invited to an oral information by participating centres. Of them, 44% of women came to the dedicated medical visit. Uptake of drug prevention trial was 32 % of orally informed women and 15 % of overall eligible women. Main reasons of refusal were: potential side effects, probability to receive the placebo and lack of support from the women's physicians. Prior prophylactic oophorectomy and history ***of previous unilateral breast cancer were more frequent in women enrolled in the ONCO-03/LIBER trial than in the French cohort (93% versus 60% and 50 % versus 39 %, respectively), suggesting a higher motivation for medical prevention in these subgroups of patients.
Conclusion: One third of women with a BRCA1/2 mutation are eligible to the ONCO-03/LIBER prevention trial. 32 % of orally informed women and, only 15% of overall eligible women entered the trial. To reach accrual objective (n=308), a greater information of the trial should be offered to women with BRCA1/2 mutation and the trial has been proposed to other countries.
Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr OT2-04-03.
OT2-07-02: SWOG S0927: A Randomized Double Blind Placebo-Controlled Trial of Omega-3-Fatty Acid for the Control of Aromatase Inhibitor (AI)-Induced Musculoskeletal Pain in Women with Early Stage Breast Cancer.
Authors: Hershman DL , Unger JM , Crew KD , Moinpour CM , Minasian LM , Hansen L , Lew DL , Kaberle K , Wade JL , Meyskens FL 
Published: June 2012

Abstract
Background: Despite the well-proven efficacy of aromatase inhibitors(AIs) for the treatment of hormone-sensitive breast cancer, a significant number of women suffer from musculoskeletal side-effects which can result in early discontinuation of this important medication. Given the proposed anti-inflammatory effects of omega-3-fatty acid and the paucity of therapeutic options for AI-induced arthralgia, it is therefore reasonable to test the efficacy of omega-3-fatty acid in women with breast cancer who have developed moderate to severe joint symptoms after initiating AIs.
Specific aims: To assess if omega-3-fatty acid as compared to placebo causes a reduction in worst joint pain/stiffness in women with AI-associated arthralgias at 12weeks as measured by the modified Brief Pain Inventory (BPI). Additional measures will include the WOMAC, M-SACRAH, FACT-ES and global rating of change, which will be assessed at baseline, 6, 12 and 24 weeks. We will evaluate fasting lipids, hormone levels, serum inflammatory markers (TNF, IL2, CRP), and markers of joint destruction (CTX-II) at baseline, 12 and 24 weeks.
Eligibility criteria:Pts. must have histologically-confirmed stages I-III breast cancer, with no evidence of metastatic disease and undergone definitive breast cancer surgery. Pts must be post-menopausal and currently be taking a third-generation AI —anastrazole(Arimidex®), letrozole (Femara®), or exemestane (Aromasin®) for at least the previous 90 days prior to registration with plans to continue for at least an additional 180 days after registration.The patient must have a worse joint pain/stiffness score of 5 or greater on the 10-point scale of the BPI which started or increased after initiation of AI. Pts must not have taken omega-3-fatty acid supplements within the past 3 months prior to registration.Pts will be randomized to receive 6 capsules daily (at 1,000 mg each; ∼600mg combination of ethyl esters EPA/DHA) of omega-3-fattyacid or matching placebo daily for 24 weeks. Statistical methods:We stipulate an alpha=.05 two-sided test, with an estimated 5% non-adherenceand 20% dropout rate at the primary endpoint evaluation time of 12 weeks after randomization. For a two point difference in worst joint pain/stiffness and a 3.5 point SD at 12 weeks, 222 eligible patients would be required for 90% power under a two-arm normal design. To allow ineligibility rate of 10%, 246 total pts will be enrolled. The study should be activated September 2011. Funding: Supported by National Cancer Institute grant CA037429
Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr OT2-07-02.
OT3-01-08: Phase II Study of S-1 Combined with Cisplatin in the First-Line Treatment of Triple Negative Breast Cancer.
Authors: Fan Y , Xu BH 
Published: June 2012

Abstract
Rationale: There is no standard choice of first-line treatment for triple negative breast cancer (TNBC). It is supposed that TNBC may be more sensitive to DNA damage agents such as platinum but resistant to cell cycle specific agents including taxanes and 5-fluorouracil. Currently these hypotheses are under investigation in several ongoing clinical trials. S-1 is an orally administered fluorinated pyrimidine with high activity in non-small-cell lung cancer and gastric cancer. Recently single agent S-1 has been reported to be effective in capecitabine-resistant metastatic breast cancer with a response rate of 27.8% and median TTP of 6.2 months. So it is intriguing to find whether S-1 plus cisplatin would be a valuable regimen in TNBC patients with limited choices of management.
Design: This is a prospective, single-arm phase II study. Eligible patients are treated first with S-1( 80mg/m2, 2 weeks on and 1 week off) and cisplatin (75mg/m2 intravenously day1) every 3 weeks as a cycle for up to 6 cycles, until disease progression, unacceptable toxicity or patient consent withdrawal. If no PD was observed after 6 cycles, patients can remain on S-1 until disease progression, unacceptable toxicity or patient consent withdrawal.
Eligibility: Major inclusion criteria includes: 1. histologically confirmed triple negative breast cancer; 2. advanced patients without prior treatment for locally recurrent or metastatic disease; 3. patients must have received anthracyclines and taxanes in neo/adjuvant setting; 4. at least one measurable disease according to RECIST 1.1; 5. adequate organ function within acceptable range.
Endpoints: The primary endpoint is objective response rate (ORR) and secondary endpoints include progression free survival (PFS), overall survival (OS) and safety profile. Exploratory biomarks will be studied for TS and DPD enzyme expression and genotyping.
Statistical considerations: The expected response rate is around 50% based on the literature, and the null hypothesis is based on a response rate no greater than 30%. According to Simon's two stage phase II design with errors of 0.05 and 0.20 respectively, a minimum of 15 patients would be required in the first stage and totally 46 patients after the second stage. Since a non-compliance rate of 10% is expected, we plan to enroll a total of 50 patients.
Recruitment: Currently it has just been initiated with 1 patient still on screening. The target accrual, as stated above, is 50 patients.
Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr OT3-01-08.
OT3-01-11: A Randomized, Phase II Multicenter, Double-Blind, Placebo-Controlled Trial Evaluating MetMAb and/or Bevacizumab in Combination with Weekly Paclitaxel in Patients with Metastatic Triple-Negative Breast Cancer.
Authors: Daniel BR , Campone M , Dieras V , Ervin T , Yu W , Paton VE , Xia Q , Peterson A 
Published: June 2012

Abstract
Background
Dysregulation of the HGF/Met pathway has been associated with tumorigenesis in many malignancies, including the basal sub-type of triple-negative breast cancer. MetMAb (RG3638) is a recombinant, humanized, monovalent monoclonal antibody directed against Met. By binding to the extracellular domain of Met, MetMAb selectively blocks ligand binding and subsequent activation by HGF. Pre-clinical data support the efficacy of combining MetMAb with numerous chemotherapy agents and with targeted agents including bevacizumab and erlotinib. In clinic, MetMAb has been generally well tolerated as a single agent (Phase I), in combination with bevacizumab (Phase Ib) and with bevacizumab in a dose escalation/expansion study (Phase Ib)1 as well as in combination with erlotinib in patients with previously treated NSCLC2. The combination of MetMAb + erlotinib in NSCLC demonstrated significant benefit in both PFS and OS in patients with Met diagnostic positive tumors whereas those patients with Met diagnostic negative tumors demonstrated a detrimental effect in both PFS and OS. The most commonly reported adverse events associated with MetMAb are peripheral edema and fatigue.
Methods: This clinical trial is a randomized three-arm Phase II study in patients with triple-negative metastatic breast cancer, which makes up the majority of basal sub-type breast cancer. Patients will be randomized (1:1:1) to either paclitaxel + bevacizumab + placebo; paclitaxel + placebo + MetMAb; or paclitaxel + bevacizumab + MetMAb. The primary endpoint of this study is PFS in all patients and by Met diagnostic status. Secondary endpoints include an evaluation of OS, ORR, safety, and pharmacokinetics. To date, 11 patients have been enrolled, and 10 patients have been treated.
Primary and secondary analyses will include all randomized patients, with patients analyzed according to the treatment arm to which they were assigned. Kaplan-Meier methodology will be used to estimate the median PFS for each treatment arm. An estimate of the HR with 95% CI will be determined using a Cox regression model with an indicator variable for the MetMAb-containing arm. Safety will be assessed through summaries of adverse events and will include all patients who receive any amount of study treatment.
This study remains open for accrual; further details on the trial can be found on the ClinicalTrials.gov website under NCT01186991.
1. Moss et al, In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2–6; Orlando, FL; AACR 2011 (abstr 4717).
2. Spigel et al, J Clin Oncol 29:2011 (suppl; abstr 7505).
Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr OT3-01-11.
OT3-02-02: Yoga Compared to Exercise as a Therapeutic Intervention during (Neo)adjuvant Chemotherapy in Women with Stage I-III Breast Cancer.
Authors: Wiedemann F , Büssing A , Halle M , Kiechle M , Kohls N , Ostermann T , Sattler D , Ettl J 
Published: June 2012

Abstract
Background: Psychological and physical distress is high in breast cancer patients receiving neoadjuvant or adjuvant chemotherapy. The ***patients'ability to cope with this distress has an impact on treatment variables, i.e. deliverable chemotherapy dose, tolerabilty of side effects, and finaly treatment completion rate. Exercise intervention studies have shown physiological and psychological benefits when undertaken during cancer treatment. There is also evidence that mind/body interventions such as yoga are useful to manage treatment-related symptoms and anxiety in breast cancer patients. Considering the specific theoretical background of mind/body interventions this ongoing trial aims to elucidate the different effects of yoga and conventional exercise on physical and psychological factors in breast cancer patients undergoing neoadjuvant or adjuvant chemotherapy. Trial design: Longitudinal data collection within an open, prospective, randomized trial using standardized questionnaires about inner correspondence and peacefulness with practices (ICPH), health-related quality of life (EORTC QLC C-30), fatigue (Cancer Fatigue Scale, CFS-D), mindfulness (Freiburg Mindfulness Inventory, FMI), spiritual/religious attitudes and disease coping (SpREUK), and life satisfaction (Brief Multidimensional Life Satisfaction Scale, BMLSS). Patients with newly diagnosed stage I-III breast cancer undergoing neoadjuvant or adjuvant chemotherapy are randomly assigned to receive yoga or conventional exercise on a 1:1 ratio. The yoga intervention consists of a weekly 60-minute Iyengar-Yoga group-session together with individual home-based, selfcontained 20-minute sessions twice a week. The conventional exercise intervention consists of a weekly 60-minute physiotherapy exercise session together with individual home-based, selfcontained 20-minute sessions twice a week. Data assessments via questionnaires are done at baseline, right after the 12-week intervention period and 2 months after the end of intervention. Statistical analysis includes analysis of variance with all collected parameters and analysis of correlation between ICPH and above parameters. For statistical power 1-β=0.8 and twosided probability of error a=0.05 the target accrual is 120 patients. Patient accrual within two breast care units started in April 2011 with 12 patients being on study to date (2011, June 21). Planned period of accrual is 20 months.
Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr OT3-02-02.