bluuebunny/crossref_metadata_2025_split huggingface dataset:
Masitinib in comparison to imatinib as first-line therapy of patients with advanced gastrointestinal stromal tumor (GIST): A randomized phase III trial.
Authors: Adenis Antoine , Chaigneau Loic , Michel Pierre , Isambert Nicolas , Bertucci François , Bui Nguyen Binh , Bouche Olivier , Mineur Laurent , Bekaii-Saab Tanios S. , Penel Nicolas , Acin Yolene , Moussy Alain , Hermine Olivier 
Published: March 2020

TPS10102^ Background: Masitinib is an oral tyrosine kinase inhibitor (TKI) that has greater in vitro kinase activity and/or selectivity than imatinib against KIT and PDGFRA/B. A phase 2 study has previously reported that masitinib treatment produced clinically relevant activity in imatinib-naïve patients with advanced GIST. Considering the promising long term response observed in overall survival (OS) (see Table) there is compelling evidence to compare masitinib against imatinib (the current standard of care) in the first-line setting. Methods: A multicenter, randomized, open label, phase 3, 1:1 study to compare efficacy and safety of masitinib (7.5 mg/kg/day) to the active control of imatinib (400 or 600 mg/day) in first-line treatment of patients with advanced GIST. Primary endpoint is progression-free survival (PFS), with secondary endpoints including OS, time to progression (TTP), and clinical response rates (RECIST). Based on a planned sample size of 222 patients (111/arm) this 15% non-inferiority study was designed to have an 85% power using a 95% two-sided CI of the hazard ratio. Patient eligibility criteria include: histologically proven, metastatic or locally advanced nonresectable, or recurrent post-surgery GIST; TKI naïve patient or patient previously receiving imatinib only as a neoadjuvant or adjuvant therapy; and confirmed KIT-positive or PDGFRA-positive tumors. Recruitment is ongoing. On 09/2011, the DMC recommended continuation of this study. Clinicaltrial.gov: NCT00812240. [Table: see text]
The PARSC trial, a prospective study for the assessment of recurrence risk in stage II colon cancer patients using ColoPrint.
Authors: Salazar Ramon , Marshall John , Capdevila Jaume , Glimelius Bengt , de Waard Jan Willem , Van Der Hoeven Jacobus , Klaase Joost , Bibeau Frédéric , Bachleitner-Hofmann Thomas , Midgley Rachel A , Levine Edward Allen , Law Wai Lun , Asano Michio , Chang George J. , Cohen Stephen M , Beart Robert W. , Goldfarb Paul M. , McCarter Martin , Stork-Sloots Lisette , Rosenberg Robert 
Published: March 2020

TPS10632 Background: An 18-gene expression profile, ColoPrint, has been developed for identifying colon cancer patients more likely to develop recurrent disease and who would be candidates for adjuvant chemotherapy. The gene signature was validated in public datasets and independent patient cohorts (stage II and III patients). Uni-and multivariate analysis was performed on the pooled stage II patient set (n=320) (median follow-up 70 months). ColoPrint classifies 65% of stage II patients as Low Risk. The 3-year RFS was 91% for Low Risk and 74% for High Risk patients with a HR of 2.9 (p=0.001). ColoPrint was the only significant prognostic marker in the subgroup of patients with T3-MSS phenotype (Tabernero, ASCO GI 2012). Methods: A blinded prospective trial, PARSC (Prospective study for the Assessment of Recurrence risk in Stage II colon cancer patients) using ColoPrint has been initiated. Objectives are: (1)To validate the performance of ColoPrint in estimating the 3-year relapse rate in patients with stage II colon cancer. (2) To compare the risk assessment in stage II patients using the ColoPrint profile vs a clinical risk assessment based on Investigator’s assessment of risk and ASCO high-risk recommendations. (3) To investigate therapy as a potential confounding factor for ColoPrint results. (4) To assess the performance of ColoPrint in estimating the 3-year relapse rate in patients with stage III colon cancer. Inclusion criteria: age ≥ 18 years, adenocarcinoma of the colon, stage II and III, no prior neo-adjuvant therapy, no synchronous tumors, fresh tumor sample, and written informed consent. The treatment of the patient is at the discretion of the physician adhering to National Comprehensive Cancer Network (NCCN)-approved regimens or a recognized alternative (blinded for ColoPrint result). The trial started in Sept. 2008 with currently 32 participating sites in 11 countries. Thus far, 340 eligible stage II and 280 stage III patients have been enrolled. The aim is to enroll 575 stage II patients. Clinical trial registry number: NCT00903565.
ACRIN 6684 assessment of tumor hypoxia in glioblastoma using 18F-fluoromisonidazole with PET and MRI.
Authors: Gerstner Elizabeth Robins , Zhang Zheng , Fink James R , Sorensen Gregory A , L'Heureux Darryl , Heckel Martha L. , Dunning Bernadine , Muzi Mark , Mankoff David A. , Barboriak Daniel 
Published: March 2020

TPS10635 Background: Glioblastoma (GBM) is an aggressive type of primary malignant brain tumor and despite treatment with surgery, radiation, and temozolomide (TMZ) chemotherapy, median overall survival (OS) remains poor. A pathologic hallmark of GBM is tumor necrosis, a suspected result from endogenous tumor hypoxia. Angiogenesis is stimulated by hypoxia-driven signaling cascades and is required for tumor proliferation. The inefficient blood supply of these hypoxic tumors also limits the efficacy of chemotherapy and radiotherapy. Surviving hypoxic tumor cells may be selected out and proliferate as a more aggressive tumor subtype, therefore hindering OS. 18F-Fluoromisonidazole (FMISO) is a PET radiotracer whose uptake in hypoxic tissues can be measured radiographically. The degree of tumor hypoxia has been negatively associated with time to tumor progression and survival (Spence et al, 2008). Knowledge of the degree/distribution of tumor hypoxia by PET uptake and perfusion MRI parameters may provide prognostic information and help guide therapy for patients with GBM. Methods: In this phase II prospective single arm multi-institution study, patients will undergo baseline FMISO PET and MR imaging two weeks prior to chemoradiotherapy (CRT). A subset of patients will receive a second FMISO PET one week prior to CRT to assess reproducibility. Clinical outcomes of OS and 6-month progression-free survival (PFS-6) will be correlated to PET and MRI parameters. Eligibility: Pathologically confirmed GBM with residual tumor after surgery (including T2/FLAIR hyperintensity consistent with tumor) scheduled to receive standard fractionated radiation therapy and temozolomide alone or with an anti-VEGF agent or PARP inhibitor. Current enrollment: 22 patients of 50 sample size Contact information: Please contact the PI, Elizabeth R. Gerstner, MD ( egerstner@partners.org ) for additional information. Significance: With a better understanding of the extent of tumor hypoxia and changes in hypoxia levels from treatment, more effective therapies could be developed to inhibit GBM growth, target hypoxic areas and individualize patient care.
Phase II neoadjuvant trial with carboplatin and eribulin mesylate in patients with triple-negative breast cancer.
Authors: Barnato Sara E. , Jeruss Jacqueline Sara , Bethke Kevin P. , Hansen Nora M. , Khan Seema Ahsan , Von Roenn Jamie H. , Rosen Steven T. , Gradishar William John , Siziopikou Kalliopi P. , Meservey Caitlin , Kaklamani Virginia G. 
Published: March 2020

TPS1134 Background: Several neoadjuvant trials have been conducted in triple negative breast cancer (TNBC) with platinum agents with pathologic complete response (pCR) ranging from 16%-32%. Eribulin mesylate, a nontaxane microtubule dynamics inhibitor, has clinical activity as monotherapy in breast cancer and other solid tumors. A recent phase I trial found the combination of eribulin mesylate with carboplatin was well tolerated and showed activity in advanced solid tumors. The recommended dose for future trials was eribulin mesylate 1.1 mg/m2 and carboplatin AUC6. We proposed a neoadjuvant phase II trial with the combination of carboplatin and eribulin in patients with TNBC. Methods: This is a non-randomized, open-label, multi-center, phase II clinical trial of eribulin and carboplatin enrolling histologically-confirmed TNBC patients. Our primary endpoint is to determine the pCR in TNBC patients treated with the combination of carboplatin and eribulin. Secondary endpoints include determination of the clinical response rate, toxicity evaluation and measurement of stem cell and TLE3 as a biomarker of response to eribulin therapy. To obtain an alpha of 0.10 and a power of 0.90, a sample size of 30 patients is required to detect a pCR rate >=30%. 10 of the planned 30 patients have been enrolled to date. Treatment will be given every 3 weeks for a total of 4 cycles of therapy. There will be an initial safety run-in to evaluate the appropriate dose of eribulin in this population. The first 10 patients will receive eribulin at 1.4 mg/m2 (intravenously over 2-5 minutes) followed by carboplatin AUC=6 (intravenously over 30 minutes). After the 10th patient has been enrolled, the study will be temporarily suspended pending review; toxicity will be assessed for these first 10 patients (cycle 1 only) to assess whether this dose of eribulin will be used for the remaining patients or if a reduction to a dose of 1.1 mg/m2 will be required. Definitive surgery will be performed 3-8 weeks after completion of therapy, which will conclude the duration of the study. Clinical Trial Registry Number NCT01372579.
Neoadjuvant bevacizumab with weekly nab-paclitaxel plus carboplatin followed by doxorubicin plus cyclophosphamide (AC) for triple-negative breast cancer.
Authors: Snider Jessica N. , Young Robyn R. , Schwartzberg Lee Steven , Allen Jeffrey Warren , Javed Yasir Ahmed , Jahanzeb Mohammad , Sachdev Jasgit C. 
Published: March 2020

TPS1137 Background: Triple negative breast cancer (TNBC) predominantly clusters with “basal like” subtype on genomic profiling. Over-expression of Secreted Protein Acidic and Rich in Cysteine (SPARC) has been observed in basal like breast cancer (Charaffe-Jaufrett et al. Oncogene 2006; 2273-84). Endothelial transcytosis of nab- paclitaxel occurs via albumin- gp60 receptor-caveolin 1 interaction. SPARC entraps the albumin resulting in higher intratumoral accumulation, which may explain the increased efficacy of nab-paclitaxel (Desai et al. Translational Oncology 2009; 59-63). Exploiting this mechanism and the dysfunctional BRCA mediated DNA repair in basal tumors, we hypothesize that nab-paclitaxel + the DNA damaging drug carboplatin would produce high response rates in TNBC. Adding bevacizumab may enhance efficacy by blocking angiogenesis. In TNBC, pathologic complete remission (pCR) to neo-adjuvant therapy correlates with better disease-free survival (DFS). We hypothesize that high pCR rates can be achieved for patients with TNBC with this combination translating to an improved DFS than seen historically. Methods: Patients with palpable and operable TNBC ≥ 2 cm are eligible for this single stage phase II trial. pCR (defined as the absence of invasive tumor cells) in the breast is the primary end point, while pCR in the breast + axillary nodes and pCR + near pCR (residual tumor < 5mm) in the breast are secondary end points. 57 evaluable patients are needed, assuming a pCR rate of 25% vs. 40% for the null and alternate hypotheses respectively. 34 patients have been accrued to date. Patients receive carboplatin AUC 6 day 1 and nab-paclitaxel 100mg/m2 days 1, 8 and 15 of a 28 day cycle for 4 cycles and then dose dense AC for 4 cycles. Bevacizumab is given at 10mg/kg Q 2 weeks with chemotherapy for the first 6 cycles. Surgery and radiation are per institutional standards. Bevacizumab is continued postoperatively to complete 1 year of treatment. A core biopsy for collection of fresh tumor tissue is required prior to the start of study treatment. Blood is collected at baseline, and after 4 and 8 cycles for biomarker analysis. Gene expression profiling will be undertaken for correlation with response.
Randomized controlled trial comparing zoledronic acid plus chemotherapy with chemotherapy alone as a neoadjuvant treatment in patients with HER2-negative primary breast cancer.
Authors: Kohno Norio , Hasegawa Yoshie , Horiguchi Jun , Ishikawa Takashi , Miura Daishu , Hayashi Mitsuhiro , Takao Shintaro , Kim Seung Jin , Tanino Hirokazu , Akazawa Kohei 
Published: March 2020

TPS1141 Background: Zoledronic acid (ZOL) is a nitrogen-containing bisphosphonate, and it induces osteoclast apoptosis and inhibits bone resorption by inhibiting the mevalonate pathway. ZOL has also been found to have antitumor effects that include an angiogenesis inhibiting action, an inhibitory effect on tumor cell adhesion to and invasion of the extracellular matrix, and activation of a gdT cells. In addition, it has been found to have a synergistic apoptosis-inducing effect when used in combination with antitumor drugs. In this study we will investigate the pCR rate when ZOL is added to anthracycline followed by taxane to treat T2 and T3 breast cancer patients. Methods: Women with resectable invasive StageIIA-IIIB (T ≥ a3 cm or T ≥ a2 cm and lymph node positive) breast cancer who are HER-2-negative, between 20 and 70 years of age, and ECOG PS 0-1 are eligible. Patients with distant metastasis, patients who have had received chemotherapy, hormone therapy, or radiotherapy for breast cancer, patients with serious complications, such as heart disease or an infection, patients with a complicating dental or jaw infection or traumatic condition of the teeth, and patients with a history of treatment with a bisphosphonate within the previous 12 months are excluded. A total of 4 courses of FEC100 are administered every 3 weeks followed by weekly paclitaxel for 12 courses. ZOL 4mg is administered every 3-4 weeks a total of 7 times. Patients are randomized 1:1 to chemotherapy + ZOL group or chemotherapy alone group, according to the presence or absence of lymph node metastasis, estrogen receptor (ER) status, and their menopausal status. The primary endpoint is pCR. Secondary endpoints are tumor response rate, the breast-conserving surgery ratio, and disease-free survival (DFS). We calculated the sample size on the basis of a pCR rate of 18% in the chemotherapy alone group and 35% in the chemotherapy + ZOL group, at a one-sided significance rate of 5%, and test power of 80%, and as a result we will target a patient sample size of 180 patients. 162 of planned 180 patients have been enrolled as of January 24, 2012.
IBL2001: Phase (ph) I/II study of a novel dose-dense (dd) schedule of indibulin for the treatment of metastastic breast cancer.
Authors: Traina Tiffany A. , Hudis Clifford , Gonzalez Joseph , Anthony Stephen Patrick , Smith David A. , Chandler Jason Claud , Jac Jaroslaw , Youssoufian Hagop , Norton Larry 
Published: March 2020

TPS1143 Background: Indibulin (Zybulin, ZIO‑301) is a new, synthetic agent that inhibits tumor cell growth at the G2/M phase through destabilization of microtubule dynamics. It binds tubulin at a different site than taxanes and vinca alkaloids. Indibulin does not interact with acetylated (neuronal) tubulins and has not exhibited the neurotoxicity associated with other tubulin binders. Indibulin has potent antitumor activity in human cancer cell lines, including multidrug-, taxane-, and vinblastine-resistant lines. Norton-Simon modeling based on cell line data suggested that dd administration could optimize efficacy while limiting toxicity. Methods: Eligible are patients (pts) with metastatic or unresectable locally advanced breast cancer, measurable or non-measurable disease, and any number of prior therapies. The objective of the Ph I portion is to determine the maximum tolerated dose (MTD) of indibulin when given in a dd fashion (5 days treatment, 9 days rest (14 total) using standard 3+3 dose escalation schema. Ph II will seek to estimate the proportion of pts progression free at 4 months when treated with indibulin at the dose determined in the Ph I. Secondary endpoints are overall response rate, proportion of subjects with stable disease >6 months and toxicity profile of indibulin. Optimal Simon two-stage design with an unpromising rate of pts who have not progressed at four months as 20% and a promising rate of 40% with a type I error of 5% and power of 80% will be used. 13 pts will initially enter the 1st stage of the ph II portion. If there are 3 or fewer pts who do not experience disease progression at 4 months in the first stage of ph II, the study will be terminated and declared to have a negative result. If 4 or more pts do not progress at 4 months, enrollment in the ph II of the study will be extended to 43 pts. A total of 45 pts will be enrolled to allow for a 5% drop out rate to account for pts who may not be evaluable for the primary endpoint due to toxicity or study withdrawal rather than progression of disease or death prior to 4 months. If ≥13 out of 43 pts are progression-free at 4 months, the study will be considered to have a positive result and indibulin would be considered worthy of further testing in this disease.
A phase II, single-arm, feasibility study of dose-dense doxorubicin and cyclophosphamide (AC) followed by eribulin mesylate for the adjuvant treatment of early-stage breast cancer (EBC).
Authors: Traina Tiffany A. , Hudis Clifford , Lehman Robert , Rege Jessicca , Wang Wenquan , Cox David , Seidman Andrew David 
Published: March 2020

TPS1145 Background: Randomized trials have confirmed the benefit of the combination of an anthracycline (A) and cyclophosphamide (C) for the adjuvant treatment of EBC. The addition of taxane therapy to AC therapy has further improved survival. Despite the improvement in adjuvant therapies for BC, new approaches for improving outcomes are of significant importance and may involve developing improved combination regimens. Eribulin mesylate has demonstrated antitumor activity and significant improvement in overall survival (OS) in patients with heavily pretreated locally advanced or metastatic breast cancer (MBC) and may improve outcomes in EBC as well. Methods: This study will determine the feasibility of eribulin as adjuvant therapy following dose-dense AC for HER2 normal EBC. A completion rate of >80% was set as a threshold for feasibility as established adjuvant regimens have shown feasibility rates ranging from ~65% for trastuzumab to >80%. This is a phase 2, single-center, feasibility study of dose-dense adjuvant chemotherapy in patients with EBC. Dose-dense AC (Doxorubicin 60 mg/m2 IV plus C 600 mg/m2 IV) on day 1 of every 14-day cycle is given for 4 cycles, followed by 4 cycles of eribulin mesylate at 1.4 mg/m2 over 2-5 minutes IV on days 1 and 8 every 21 days. Growth factors are given on day 2 of AC cycles and only for neutropenia events with eribulin treatment. Feasibility is determined by the ability to complete the eribulin portion of the regimen without a dose delay or reduction. Exploratory objectives include efficacy endpoints of 3-year disease-free survival (DFS) and OS. Patients have histologically confirmed HER2 normal stage I-III invasive disease and adequate bone marrow, liver, and renal function. Thirty two of approximately 80 planned patients are currently enrolled. Feasibility rates will be calculated with growth factor support (ie, the successful use of growth factor support following a neutropenia event is not considered a dose delay)and without growth factor support (ie, where need for growth factors is considered a delay). Secondary endpoints include DFS and OS and will be estimated by Kaplan-Meier method.
A multicenter prospective study of image-guided radiofrequency ablation for small breast carcinomas.
Authors: Kinoshita Takayuki , Yamamoto Naoto , Fujisawa Tomomi , Takabatake Daisuke , Wada Noriaki , Masuda Norikazu , Tsuda Hitoshi , Doihara Hiroyoshi , Takahashi Masato 
Published: March 2020

TPS1147 Background: As the management of breast carcinoma evolves toward less invasive treatments, the next step is the possibility of removing the primary tumor without surgery. The most promising noninvasive ablation technique is radiofrequency ablation (RFA), which can effectively kill tumor cells with a low complication rate. Our preliminary studies of RFA followed by standard surgical resection have indicated that this technique is effective for surgical ablation of small (≤ 2cm) breast tumors without extensive intraductal components (EIC). Methods: To determine if RFA is oncologically and cosmetically appropriate for the local treatment of primary breast carcinoma, this multi-center prospective study used RFA as the sole local treatment of breast tumors ≤ 1.5cm in size on ultrasound and MRI. Exclusion criteria include receiving of preoperative chemotherapy, or the presence of invasive lobular carcinoma or invasive ductal carcinoma with suspicious EIC. After confirmation that the standard baseline core biopsy for diagnosis and measurement of tumors markers (ER, PgR, HER-2/neu expression and the presence of the Ki-67 proliferative marker) have been obtained, consent will be obtained and the patient scheduled RFA. All patients received adjuvant radiation therapy. The use and choice of systemic therapy will be based on the information from the baseline core biopsy and imaging studies. The first primary endpoints of this study is successful tumor ablation, as evidenced by negative findings on vacuum-assisted or core biopsies and imaging studies after RFA. The second primary endpoints is the incidence of procedure related adverse events. Forty patients with small tumors that are clearly identifiable and measurable by ultrasound and MRI were enrolled. The response to ablation was evaluated with both vacuum-assisted or core biopsies and imaging studies every 3 months during the first year. The long-term outcomes were assessed using quality of life measurement scales and imaging studies every 6 months thereafter through year 5.