bluuebunny/crossref_metadata_2025_split huggingface dataset:
A randomized phase II clinical trial of enzalutamide in combination with the therapeutic cancer vaccine, PSA tricom, in metastatic, castration resistant prostate cancer.
Authors: Singh Nishith K. , Kim Joseph W. , Heery Christopher Ryan , Dahut William L. , Couvillon Anna , Rauckhorst Myrna , McMahon Sheri , Schlom Jeffrey , Fojo Tito , Arlen Philip M. , Gulley James L. , Madan Ravi Amrit 
Published: March 2020

TPS5104 Background: There is a strong rationale to combine therapeutic cancer vaccines with hormonal abrogation in prostate cancer. Androgen abrogation augments T-cell trafficking to prostate, decreases immune tolerance, increases production of naïve thymic T-cells, enhances cytotoxic T-cell repertoire. PSA TRICOM (PROSTVAC) is a therapeutic, viral-vector based, off-the-shelf, cancer vaccine of PSA & 3 co-stimulatory molecules in phase III testing. This was developed at the NCI in collaboration with Bavarian Nordic Immunotherapeutics. It has demonstrated safety and survival benefit in a randomized phase 2 trial of metastatic castrate resistant prostate cancer (mCRPC). Enzalutamide is a modern androgen receptor inhibitor (ARI) approved for the treatment of mCRPC. Data from the clinical trials with these therapies suggest good individual tolerability without any overlapping toxicities. Analysis of previous trials suggests that vaccines may enhance clinical outcomes with ARI. These data form the scientific basis for a combination approach of a cancer vaccine with ARI to control tumor progression in mCRPC. Methods: A randomized, phase 2, open-label clinical trial at the NCI will enroll 72 chemo-naïve, minimally symptomatic patients with mCRPC. They will be randomized (1:1) to enzalutamide (160 mg daily) alone, or enzalutamide with PSA TRICOM for treatment until radiographic progression. PSA-TRICOM will be administered in a core phase (with day 1, 15 and 29 then 4 additional monthly boosts) followed by continued boosts every 3 months. The primary end point will evaluate time to progression in each arm with secondary endpoints including overall survival and systemic immune responses (lymphocyte subsets, regulatory T-cells, regulatory T-cell function, cytokines, naïve thymic emigrants). If a therapeutic cancer vaccine can enhance the clinical efficacy of a hormonal agent such as enzalutamide, it may help define a new role for vaccines as an adjuvant to standard therapies. We will also evaluate this combination in a second trial in non-metastatic, castration-sensitive patients where this combination may yield its greatest clinical impact.
Phase II study of de-intensification of radiation and chemotherapy for low-risk HPV-related oropharyngeal squamous cell carcinoma.
Authors: Chera Bhishamjit S. , Qaqish Bahjat F. , Weissler Mark C , Hayes David N. , Shores Carol G. , Monroe Alan , Anderson Roger F. , Wu Justin , Grilley-Olson Juneko E. , Weiss Jared , Hackman Trevor , Zanation Adam M , Mendenhall William M. , Amdur Robert J 
Published: March 2020

TPS6097 Background: The prognosis is excellent for low-risk human papillomavirus (HPV) associated oropharyngeal squamous cell carcinoma (OPSCC). Current standard chemoradiotherapy (CRT) regimens cure most patients but cause significant acute (mucositis) and long-term toxicities (xerostomia and dysphagia). Toxicity is primarily determined by the dose of radiotherapy and the intensity of chemotherapy. The aim of this study is to evaluate the pathological complete response (pCR) rate of low-risk HPV-associated OPSCC after de-intensified CRT. Methods: The major inclusion criteria are: 1) T0-T3, N0-N2c, M0, 2) HPV or p16 positive, and 3) </= 10 pack-years smoking history. Patients receive 60 Gy of intensity modulated radiotherapy (IMRT) with concurrent weekly intravenous cisplatinum (30 mg/m2). CT scans are obtained 4 to 8 weeks after completion of CRT to assess response. All patients have a surgical resection of any clinically apparent residual primary tumor or biopsy of the primary site if there is no evidence of residual tumor and a selective neck dissection to encompass at least those nodal level(s) that were positive pre-treatment, within 4 to 14 weeks after CRT. Longitudinal assessments of quality of life (EORTC QLQ-C30 & H&N35, NDII), patient reported outcomes (PRO-CTCAE, EAT-10), and swallowing evaluations (modified barium swallow) are obtained prior to, during, and after CRT. The primary endpoint of this study is the rate of pCR after CRT. The null hypothesis is that the pCR rate for de-intensified CRT is at least 87%, the historical rate (based on the reported 3-year local regional control rate of 87% in the RTOG 0129). Power computations were performed for N=40, with a type I error of 14.2% if the true pCR rate is 0.87. The study will be done in 3 stages with 15+15+10 patients with interim analyses at 15 and 30 patients. The trial will be stopped if the pCR rate is </= 9/15 and 21/30. The null hypothesis will be accepted if the pCR rate is >/= 33/40. Clinical trial information: NCT01530997.
Ph III randomized studies of the oral pan-PI3K inhibitor buparlisib (BKM120) with fulvestrant in postmenopausal women with HR+/HER2– locally advanced or metastatic breast cancer (BC) after aromatase inhibitor (AI; BELLE-2) or AI and mTOR inhibitor (BELLE-3) treatment.
Authors: Iwata Hiroji , Baselga José , Campone Mario , Arteaga Carlos L. , Cortes Javier , Jonat Walter , De Laurentiis Michelino , Ciruelos Eva , Janni Wolfgang , Bachelot Thomas , Lonning Per Eystein , Ma Cynthia , O'Regan Ruth , Di Tomaso Emmanuelle , Bharani-Dharan Bharani , Duval Vincent , Lau Helen , Germa Caroline , Urban Patrick , Di Leo Angelo 
Published: March 2020

TPS650^ Background: The PI3K/Akt/mTOR pathway is commonly dysregulated in BC and linked to resistance to endocrine therapy, including AIs. Buparlisib is an oral inhibitor of class I PI3K isoforms (α, β, γ, δ), showing near complete tumor regression in an in vivo model of ER+ BC in combination with fulvestrant. Preliminary clinical activity in BC pts has been observed with buparlisib as a single agent and in combination with letrozole (Mayer et al. ASCO 2012). Methods: BELLE-2 (NCT01610284) and BELLE-3 (NCT01633060) are 2 Ph III randomized, double-blind, placebo-controlled trials of oral buparlisib (100 mg/d) in combination with fulvestrant (500 mg) given on D1 and 15 of Cycle 1 and D1 of each 28-day cycle thereafter in postmenopausal women with HR+/HER2– locally advanced/metastatic BC. Additional eligibility criteria: disease progression on/after AI treatment for BELLE-2; prior treatment with AI and progression on mTOR inhibitor in combination with endocrine therapy (as last therapy prior to study entry) for BELLE-3; ≤1 previous line of chemotherapy for advanced disease; available archival tumor tissue for PI3K-related biomarker analysis. Randomization to either arm (1:1 for BELLE-2 and 2:1 for BELLE-3) is stratified according to PI3K pathway activation status (activated vs non-activated vs unknown) and visceral disease status (present vsabsent). Study treatment is given until disease progression or discontinuation for any reason. Co-primary endpoints in both trials: PFS in full and PI3K pathway-activated populations based on local investigator assessment (RECIST 1.1). Key secondary endpoints: overall survival (OS) in full and PI3K pathway-activated populations; other secondary endpoints: PFS and OS in PI3K non-activated/unknown population, overall response rate, clinical benefit rate, safety (CTCAE 4.03), PK, and patient-reported outcomes (EORTC QLQ-C30 and QLQ-BR23). Estimated enrollment is 842 pts for BELLE-2 and 615 for BELLE-3. As of January 2013, 96 pts were randomized to BELLE-2 and 1 pt to BELLE-3. Recruitment is ongoing globally. Clinical trial information: NCT01610284 and NCT01633060.
UNIRAD: Multicenter, double-blind, phase III study of everolimus plus ongoing adjuvant therapy in ER+, HER2- breast cancer.
Authors: Bachelot Thomas Denis , Chabaud Sylvie , Martin Anne-Laure , Lemonnier J , Campone Mario , Andre Fabrice 
Published: March 2020

TPS653 Background: Advances in adjuvant treatment and highly effective endocrine therapies have resulted in better prognosis and survival among patients (pts) with hormone-receptor-positive (HR+; ER+ and/or PgR+) breast cancer (BC). Despite this, high risk pts (>3N+ and/or T3/4) are likely to relapse during/after adjuvant therapy. In a pivotal phase 3 trial (BOLERO-2), everolimus (EVE, an oral mammalian target of rapamycin [mTOR] inhibitor), plus exemestane demonstrated clinical efficacy in postmenopausal pts with HR+, human epidermal growth factor receptor-2–negative (HER2–) advanced BC progressing on non-steroidal aromatase inhibitors. Administering EVE earlier, concurrent with adjuvant endocrine therapy (ET) may lower relapse rates, especially in pts with high and/or persistent nodal involvement after neoadjuvant therapy. This study (UNIRAD) will evaluate the safety and effectiveness of adding EVE to adjuvant ET in pts with ER+, HER2–non-metastatic BC, who are disease-free following 3y of adjuvant ET. Methods: This multi-center, double-blind, phase 3 study will randomize adult (≥18y) women with non-metastatic ER+, HER2- BC, any T, pN+(≥4 if initial therapy and ≥1 after neoadjuvant therapy), who are disease-free following 3y of adjuvant ET to EVE (10mg/d) plus ongoing ET versus placebo (PBO) plus ongoing ET for a total adjuvant therapy duration of 5y. Stratification is by country, ET (tamoxifen or aromatase inhibitors), previous adjuvant versus neoadjuvant therapy, and age (≤70 versus >70y). Follow-up will continue for 5y after treatment. The primary endpoint is disease-free survival (DFS) with EVE versus PBO. Secondary endpoints include overall survival (OS), event-free survival, distant metastasis-free survival, DFS and OS in selected subgroups, safety, incidence of secondary cancers, quality of life, and predictive value of mTOR activation markers on DFS. Results: Accrual to the UNIRAD study will begin in March 2013 (planned N = 1984). Updated information will be presented. Clinical trial information: 2012-003187-44.
OPTIMA prelim: Optimal personalized treatment of early breast cancer using multiparameter tests.
Authors: Stein Rob , Makris Andreas , Hughes-Davies Luke , Campbell Amy Frances , Marshall Andrea , Bartlett John M. S. , Donovan Jenny , McCabe Christopher , Cameron David A. , Canney Peter , Francis Adele , Morgan Adrienne , Pinder Sarah , Rea Daniel , Hall Peter , Stallard Nigel , Higgins Helen B , Hulme Claire , Harmer Victoria , Dunn Janet A. 
Published: March 2020

TPS656 Background: Chemotherapy may have little effect on some subtypes of early breast cancer, identified as being hormonally responsive tumours without HER2 gene amplification and with a low or intermediate grade. Multi-parameter genomic tests such as Oncotype DX are increasingly used to identify patients for whom the addition of chemotherapy may confer little additional benefit. OPTIMA has an adaptive design seeking to advance development of personalised medicine in breast cancer by assessing the value of multi-parameter tests in a UK population of intermediate risk. Methods: OPTIMA prelim, the feasibility phase, has 3 objectives: (1) To evaluate performance and health-economics of multi-parameter tests to determine which test(s) will be used in the main trial; (2) To establish efficient and timely sample collection and analysis essential to deliver multi-parameter test driven treatment; (3) To establish the acceptability to patients and clinicians of randomisation to test-directed treatment assignment. OPTIMA prelim aims to recruit 300 patients with ER+ve HER2-ve tumours with involved nodes (pN1-2). Patients are randomized to the standard arm of chemotherapy with endocrine therapy, or to the “test-directed treatment” arm assigned to either the same chemotherapy with endocrine therapy or endocrine therapy only according to the result of an Oncotype DX test. The decision to continue to a main trial will be determined by concordance, cost and willingness of patients to be randomized to test guided treatment. Cost-effectiveness models will be based on the model developed in preparation for the OPTIMA trial, updated with contemporary evidence from the feasibility study and appropriate external data, e.g. the Ontario prospective cohort study. Results: Optima opened in Sept 2012 with 25 centres involved. To date 22 patients are registered, of which 17 have been randomised. Patient focus groups show the trial design is acceptable and has potential to reduce need for chemotherapy. TSC and DMEC agree that this is an important trial testing the feasibility within this patient population. Decision rules are challenging for this study but employment of adaptive designs gives the flexibility needed for the main trial. Clinical trial information: ISRCTN42400492.
BOLERO-4: Multicenter, open-label, phase II study of everolimus plus letrozole as first-line therapy in ER+, HER2- metastatic breast cancer.
Authors: Gradishar William John , Bachelot Thomas Denis , Saletan Stephen , Graham Anne Marie , Liedke Pedro Emanuel Rubini , Azevedo Sergio Jobim , Sriuranpong Virote , Cardoso Fatima 
Published: March 2020

TPS661 Background: Endocrine therapy (ET) is the standard of care for postmenopausal women with hormone receptor positive (HR+; typically, estrogen receptor [ER] positive) advanced breast cancer (ABC). However, women with HR+ ABC can progress while on ET. Crosstalk between ER signaling and the mammalian target of rapamycin (mTOR) pathway enhances tumor progression. Co-targeting these signaling pathways with the combination of everolimus (EVE), an orally bioavailable mTOR inhibitor, and ET (letrozole [LET] or tamoxifen) has been shown to significantly improve clinical outcomes in the neoadjuvant setting and in patients with HR+ ABC progressing on/after nonsteroidal aromatase inhibitors. In a pivotal phase 3 trial in women with HR+ ABC progressing on ET, EVE + exemestane (EXE) prolonged progression-free survival (PFS; local/central assessment: 7.8/11.0 mo [P < .0001]) compared with EXE alone (3.2/4.1 mo [P < .0001]). This study (BOLERO-4) will extend previous investigations to evaluate the safety and effectiveness of EVE+LET as first-line therapy in ER+ HER2– metastatic BC (mBC), and the potential benefits of continuing EVE+ET beyond initial progression. Methods: In this multicenter, open-label, international, single-arm, phase 2 study, 200 postmenopausal women age ≥18 y with ER+ HER2– mBC or locally ABC without prior therapy for advanced disease will receive EVE (10 mg/d) + LET (2.5 mg/d) until first disease progression. Upon disease progression, patients continuing in the trial will receive EVE+EXE (25 mg/d) until further disease progression. Patients who discontinue therapy in the first-line metastatic setting because of unacceptable toxicity will not be offered second-line therapy. The primary endpoint is PFS with EVE+LET in the first-line setting. Secondary endpoints include PFS in the second-line setting, overall survival, objective response rate, clinical benefit rate, safety, and the efficacy of oral dexamethasone solution to reduce the severity and/or duration of stomatitis using Oral Stomatitis Daily Questionnaire (OSDQ). Accrual across Europe, Asia, and the Americas begins Q1 2013. Estimated study completion is Q4 2015. Clinical trial information: NCT01698918.
Denosumab versus placebo as adjuvant treatment for women with early-stage breast cancer at high risk of disease recurrence (D-CARE): An international, placebo-controlled, randomized, double-blind phase III clinical trial.
Authors: Goss Paul E. , Barrios Carlos H. , Chan Arlene , Finkelstein Dianne M. , Iwata Hiroji , Martin Miguel , Braun Ada , Ding Beiying , Maniar Tapan , Coleman Robert E. 
Published: March 2020

TPS662 Background: In women with early-stage breast cancer, bone is a common site of distant recurrence and represents approximately 40% of all first recurrences. Preclinical studies demonstrated that inhibition of RANKL 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. 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 include safety, breast density, time to first on-study SRE (following the development of bone metastasis), patient reported outcomes, and biomarkers. Methods: In this international, randomized, double-blind, and placebo-controlled phase 3 trial, 4509 women with stage II or III breast cancer at high risk for recurrence and with known hormone and HERE2 receptor status were randomized. High risk was defined as biopsy evidence of breast cancer in regional lymph nodes, tumor size > 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 DCIS or LCIS) or distant metastasis, oral bisphosphonate (BP) use within 1 year of randomization, or any intravenous BP use, were not eligible. Patients were 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) were required. The trial, sponsored by Amgen Inc., began enrolling patients in June 2010 and completed enrollment in late 2012. Clinical trial information: NCT01077154.
PERSEPHONE: Duration of trastuzumab with chemotherapy in women with HER2-positive early breast cancer—Six versus twelve months.
Authors: Earl Helena Margaret , Cameron David A. , Miles David , Wardley Andrew M. , Ogburn Emma , Vallier A-L , Loi Shrushma , Higgins Helen B , Hiller Louise , Dunn Janet A. ,   PERSEPHONE Trial Group
Published: March 2020

TPS667 Background: PERSEPHONE is a randomised controlled trial comparing six months of trastuzumab to the standard 12 months in patients with HER2 positive early breast cancer. Methods: 4000 patients (pts) will be randomised into the two arms (1:1). The power calculations assume that the disease-free survival (DFS) of the standard treatment (12 months trastuzumab) is 80% at 4 years. Randomisation of 4000 pts will allow the trial to prove non-inferiority of six months trastuzumab (5% 1-sided significance and 85% power). Non-inferiority is defined as ‘no worse than 3%’ below the control arm (12 month) 4 year DFS. Primary outcome is DFS, and secondary outcomes are overall survival (OS) non-inferiority; cost effectiveness; cardiac function and quality of life. Tumour blocks are collected to research molecular predictors of survival with respect to duration of trastuzumab treatment. Blood samples are analysed for single nucleotide polymorphisms (SNPs) as pharmaco-genetic determinants of prognosis, toxicity and treatment outcome. PHARE, a similar trial from the Institut National du Cancer in France, closed to recruitment in 2010 and presented early data at ESMO 2012. Following this an unplanned interim analysis of PERSEPHONE was presented to the Data Monitoring and Safety Committee (DMSC). PERSEPHONE is funded by the NIHR HTA programme in the UK. Results: PERSEPHONE commenced recruitment in October 2007. At abstract submission, 2593 pts (65%) had been randomised from 144 UK sites. Recruitment is due to complete in September 2014 with the first planned interim analysis of the primary outcome mid-2016. The iDMSC reviewed all data available on HERA and PHARE as well as a PERSEPHONE interim analysis. There were no safety findings or signals that would warrant a change of the study plan and the high quality of data returns was noted. Conclusion: PERSEPHONE continues the active recruitment phase as planned. Preliminary but inconclusive PHARE data have reinforced interest in the PERSEPHONE trial both nationally and internationally. There has been full support from the Breast International Group (BIG) and the international breast cancer community to answer this important shorter duration question. Clinical trial information: 52968807.
EPIC: A phase III randomized, open-label study of ponatinib versus imatinib in adult patients with newly diagnosed chronic myeloid leukemia in chronic phase.
Authors: Lipton Jeffrey H. , Deininger Michael W. N. , Lustgarten Stephanie , Turner Christopher D. , Rivera Victor M. , Clackson Tim , Baccarani Michele , Cortes Jorge E. , Guilhot Francois , Hochhaus Andreas , Hughes Timothy P. , Kantarjian Hagop M. , Shah Neil P. , Talpaz Moshe , Haluska Frank G. 
Published: March 2020

TPS7129 Background: The hallmark genetic abnormality of chronic myeloid leukemia (CML), known as the Philadelphia chromosome, generates the BCR-ABL fusion gene; expression of BCR-ABL in hematopoietic stem cells gives rise to CML. Ponatinib is a potent oral pan–BCR-ABL tyrosine kinase inhibitor (TKI) that is active against native and mutated forms of BCR-ABL, including the T315I gatekeeper mutant. Results from the phase 1 and phase 2 studies of ponatinib demonstrated that ponatinib is generally well tolerated and has substantial anti-leukemic activity in patients with CML who are resistant or intolerant to prior TKI therapy, regardless of baseline mutation status. In addition, multivariate analyses suggest that ponatinib has greater activity in younger patients who are less heavily pretreated and have a shorter time since diagnosis. The phase 3 EPIC (Evaluation of Ponatinib vs Imatinib in CML) study is testing the hypothesis that ponatinib is an effective treatment for newly diagnosed chronic phase (CP) CML patients when compared with standard imatinib therapy. Methods: EPIC is a multicenter, international, phase 3, two-arm, open-label trial of ponatinib (45 mg once daily) versus imatinib (400 mg once daily) in patients with newly diagnosed CP-CML. Patients ≥18 years of age with CP-CML (diagnosed within 6 months prior to study entry) and adequate renal, hepatic, and pancreatic function are eligible for enrollment. Enrolled patients are assigned to receive ponatinib or imatinib in a 1:1 fashion, stratified by Sokal Risk score (low vs intermediate vs high). The primary efficacy endpoint for this trial is major molecular response (MMR) rate at 12 months. Secondary endpoints include MMR rate at 5 years, BCR-ABLIS<10% rate at 3 months, CCyR rate at 12 months, progression-free survival, overall survival, and safety. A sample size consisting of 480 patients will provide 90% power to detect a 15% absolute increase in MMR rate at 12 months using an unstratified Fisher exact 2-sided test at an alpha level of 0.05. Assuming a 10% dropout rate, approximately 528 patients will be enrolled. The first patient was enrolled in August 2012. Clinical trial information: NCT01650805.