bluuebunny/crossref_metadata_2025_split huggingface dataset:
Randomized phase III study of erlotinib versus observation in patients with no evidence of disease progression after first-line platin-based chemotherapy for ovarian carcinoma: A GCIG and EORTC-GCG study.
Authors: Vergote Ignace B. , Joly Florence , Katsaros Dionyssios , Coens Corneel , Reinthaller Alexander , Hall Marcia , Steer Christopher B. , Colombo Nicoletta , Lesoin Anne , Casado Antonio , Petru Edgar , Green John , Buck Martin , Ray-Coquard Isabelle Laure , Ferrero Annamaria , Favier Laure , Reed Nicholas , Curve Herve , Jimeno Antonio , Pujade-Lauraine Eric 
Published: March 2020

LBA5000 The full, final text of this abstract will be available at abstract.asco.org at 12:01 AM (EDT) on Saturday, June 2, 2012, and in the Annual Meeting Proceedings online supplement to the June 20, 2012, issue of Journal of Clinical Oncology. Onsite at the Meeting, this abstract will be printed in the Saturday edition of ASCO Daily News.
A phase Ib/II study evaluating the efficacy of doxorubicin (D) with or without a human anti-PDGFRα monoclonal antibody olaratumab (IMC-3G3) in the treatment of advanced soft tissue sarcoma (STS).
Authors: Tap William D. , Van Tine Brian Andrew , Elias Anthony D. , Livingston Michael B. , Agulnik Mark , Cooney Matthew M. , Chmielowski Bartosz , Brenner Andrew Jacob , Pennock Gregory K. , Somaiah Neeta , Dang Long H. , Tian Gary G. , Jones Robin Lewis , Okuno Scott H. , Loizos Nick , Nippgen Johannes , Schwartz Gary K. 
Published: March 2020

TPS10099 Background: PDGFRα is a receptor commonly overexpressed in STS. Olaratumab is a fully human IgG1 MAb which specifically binds to human PDGFRα and blocks PDGFR-mediated signaling pathways. Olaratumab demonstrated significant tumor inhibition as a monotherapy and in combination with standard chemotherapy in preclinical human sarcoma xenograft models. A Phase 1b/2 clinical trial for patients with advanced or metastatic STS is currently enrolling patients in 9 sites across the United States; approximately 45 patients have been randomized. Methods: In Phase 1b, patients received olaratumab (15 mg/kg) via intravenous infusion on Days 1 and 8 of each 21-day cycle and D (75 mg/m²) 1 hour after olaratumab on Day 1. Phase 1b was completed without encountering dose-limiting toxicities; enrollment into Phase 2 has begun. The primary endpoint of the Phase 2 portion is to compare progression-free survival in patients with advanced STS when treated with D plus olaratumab versus D alone. Planned enrollment goal for Phase 2 is 130 patients. Patients are required to be ≥ 18 years old with ECOG 0-2, have appropriate organ function and histologically confirmed, measurable, and advanced STS. There is no restriction on the number of prior therapies. Patients are randomized 1:1 to either D plus olaratumab (Arm A) at same dose/schedule as in Phase 1b or D alone (Arm B). All patients can receive dexrazoxane. Upon completion of 8 cycles, patients in Arm A continue with olaratumab monotherapy. Patients in Arm B who develop disease progression during or after treatment can subsequently receive olaratumab monotherapy. Patients are stratified to treatment arms according to PDGFRα expression (positive vs. negative), number of previous lines of treatment, sarcoma subtype, and ECOG performance status. Response assessment occurs every 6 weeks. Exploratory analyses include biomarkers of olaratumab pharmacodynamic activity including PDGF ligands, PDGFR downstream molecules, VEGF, and changes in vascularity of tumor specimens.
NSABP B-47: A phase III trial of adjuvant therapy comparing chemotherapy alone (six cycles of docetaxel plus cyclophosphamide or four cycles of doxorubicin plus cyclophosphamide followed by weekly paclitaxel) to chemotherapy plus trastuzumab in women with node-positive or high-risk, node-negative, HER2-low invasive breast cancer.
Authors: Fehrenbacher Louis , Jeong Jong-Hyeon , Rastogi Priya , Geyer Charles E. , Paik Soonmyung , Ganz Patricia A. , Land Stephanie R. , Costantino Joseph P. , Swain Sandra M. , Mamounas Eleftherios P , Wolmark Norman 
Published: March 2020

TPS1142 Background: Adjuvant studies utilizing trastuzumab in early HER2+ breast cancer demonstrated a large reduction in recurrence and death. Post-enrollment central testing showed HER2 non-amplified participants derived similar benefit. Methods: Selection of one of the two chemotherapy regimens is by physician choice: The non-anthracycline regimen is TC (docetaxel 75 mg/m2, cyclophosphamide 600 mg/m2) administered IV every 3 weeks for 6 cycles; the anthracycline regimen is AC followed by WP (doxorubicin 60 mg/m2 and cyclophosphamide 600 mg/m2 administered IV either every 3 weeks or every 2 weeks [per investigator discretion] for 4 cycles followed by paclitaxel 80 mg/m2 IV weekly for 12 doses). Patients are randomly assigned to receive chemotherapy with or without trastuzumab therapy. For patients receiving the TC chemotherapy regimen, trastuzumab is given every 3 weeks during and following chemotherapy until 1 year after the first trastuzumab dose (8 mg/kg loading dose; 6 mg/kg for the remaining doses). For patients receiving the AC followed by WP chemotherapy regimen, trastuzumab begins with the first dose of weekly paclitaxel and will be given weekly for 12 doses (4 mg/kg loading dose; 2 mg/kg for the remaining weekly doses). Following completion of WP, trastuzumab therapy continues with 6 mg/kg doses given every 3 weeks for a total of 1 year. Eligibility: Eligibility includes: node positive or high risk node negative female breast cancer patients; HER2 IHC 1+ or 2+ scores, but non amplified by FISH Statistical Design: The primary aim is to determine whether the addition of trastuzumab to chemotherapy improves invasive disease-free survival (IDFS). 3260 patients will be enrolled to provide statistical power of 0.9 to detect a 33% reduction in the hazard rate of IDFS using a one-sided alpha level of 0.025. Progress: Protocol was activated in January 2011. As of January 27, 2012, 486 of 3260 patients have been enrolled. Supported by NCI U10-12027, -37377, 69651, 69974, and Genentech, Inc.
ARTemis: Randomized trial with neoadjuvant chemotherapy for patients with early breast cancer.
Authors: Earl Helena Margaret , Blenkinsop C , Grybowicz L , Vallier A-L , Cameron David A. , Bartlett John M.S. , Murray Nicholas , Caldas Carlos , Thomas J , Dunn Janet A , Higgins Helen B , Hiller Louise , Hayward Larry 
Published: March 2020

TPS1144 Background: Bevacizumab is a new humanised monoclonal antibody which targets vascular endothelial growth factor (VEGF) and thereby the neoangiogenic process in cancer. Bevacizumab 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 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). Whereas the GEPARQUINTO trial reported significant benefit only in the triple negative patients (pCR 27.8% vs 36.4% p=0.021). Methods: 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. Results: Recruitment into ARTemis began in April 2009 and as of January 2012 had recruited 469 (59%). ARTemis is due to complete recruitment by Dec 2012 and the first planned interim analysis of the primary outcome will be Dec 2013. Conclusion: The IDSMC reviewed the trial in June 2011 and recommended continuation of recruitment to this important trial given there were no safety concerns, and results from the other neoadjuvant studies (NSABP-B40 and GEPARQUINTO) are conflicting.
Trial of exercise in ovarian cancer survivors.
Authors: Irwin Melinda , Gottlieb Linda , Cartmel Brenda , Ercolano Elizabeth , Rothbard Marianna , Zhou Yang , Schwartz Peter E. , Ligibel Jennifer A. , Von Gruenigen Vivian E. , Risch Harvey 
Published: March 2020

TPS1614 Background: Physical activity (PA) has been associated with improved QOL and survival in breast and colorectal cancer survivors, yet no study has examined the effect of exercise on ovarian cancer outcomes. The purpose of our NCI-funded trial is to examine, in 230 women diagnosed with Stage I-IV ovarian cancer, the impact of exercise vs. attention control on: QOL, body composition, and serum markers associated with ovarian cancer. This abstract presents preliminary recruitment and adherence results. Methods: Women are being recruited via Connecticut Tumor Registry and Yale Cancer Center into the Women’s Activity and Lifestyle Study in Connecticut (WALC). We are also recruiting patients nationally via self-referral and collaboration with medical oncologists at DFCI and Summa Akron City Hospital. Women are randomly assigned to exercise (n = 115) or attention control (n = 115). Both groups receive weekly telephone calls for six months from a certified health educator to discuss ovarian cancer health topics. In addition, the exercise group receives PA counseling to participate in 150 min/wk of aerobic exercise (primarily brisk walking) for six months. Results: Study recruitment began in March, 2010 and will be ongoing through December, 2013. As of December 31, 2011, we have identified 556 potentially eligible women. Of these, 145 are recently diagnosed and are awaiting screening, 115 were unable to be contacted, and 296 have completed the telephone screening. Of the 270, 46% were ineligible (e.g., already exercising, physical limitations); 30% were not interested, 24% (n = 66) have been randomized, and 9% (n = 24) are undergoing baseline visits. On average, women are 62 years old, diagnosed 1.8 years in the past, with primarily stage III disease. Thirty-three patients have completed the trial, with high adherence among women randomized to exercise (average 141 min/wk of exercise reported and 75% of exercisers participating in at least 150 min/wk of exercise). Conclusions: Women are interested in and able to participate in exercise after an ovarian cancer diagnosis. Our trial could suggest a unique and important role for exercise in ovarian cancer care given that physical and functional aspects of QOL are often the most compromised in ovarian cancer patients.
A phase Ib/II study testing the safety and efficacy of combined inhibition of the AKT/PI3K and AR signaling pathways in castration-resistant prostate cancer: GDC-0068 or GDC-0980 with abiraterone acetate versus abiraterone acetate.
Authors: Funke Roel Peter , Zhu Jin , Meng Raymond D. , Yan Yibing , Musib Luna C. , Talluto Craig Charles , Patel Premal H. 
Published: March 2020

TPS2616 Background: Loss of PTEN, leading to activation of the AKT/PI3K pathway is frequent and associated with poor prognosis in prostate cancer. In addition, AR and AKT/PI3K cross-regulate by reciprocal feedback and combined inhibition of both pathways resulted in improved preclinical efficacy. This study is designed to evaluate the effect of combined inhibition of AR pathway (with abiraterone) and AKT/PI3K pathway (with either GDC-0068 or GDC-0980). GDC-0068 is a potent, selective ATP-competitive inhibitor of AKT1, 2, and 3. Preclinical studies showed that cell and tumor models with PTEN loss are more likely to be sensitive to GDC-0068. GDC-0068 was generally well tolerated in phase I and a MTD of 600 mg daily was identified. GDC-0980 is a potent pan-inhibitor of Class I PI3K and inhibits wild-type and mutated p110α isoforms, as well as mTOR kinase. The recommended phase II dose (RP2D) for single-agent GDC-0980 is 40 mg daily. Methods: This study will enroll CRPC patients previously treated with docetaxel. In phase Ib, the RP2D will be determined separately for GDC-0068 and GDC-0980 in combination with abiraterone 1000 mg qd and prednisone 5mg bid. In phase II, patients will be randomized 1:1:1 to receive GDC-0068 + abiraterone, GDC-0980 + abiraterone, or placebo + abiraterone. The primary endpoint of phase II is PFS measured by PCWG2 in all patients and in patients with PTEN loss. Secondary endpoints include OS, PSA response rate, ORR, safety, Pharmacokinetics and biomarker analyses. The effect of each treatment on the number of circulating tumor cells will be assessed. Primary and secondary analyses will include all randomized patients and will be conducted according to assigned treatment arm. Kaplan-Meier methodology will be used to estimate median PFS for each arm. Up to 24 patients are planned to be enrolled in phase Ib; 240 patients (80 per arm) are planned for phase II. This study is open for accrual; to date 2 patients have been enrolled in phase Ib.
A phase I study of 1-methyl-D-tryptophan in combination with docetaxel in metastatic solid tumors.
Authors: Jackson Erica , Minton Susan E. , Ismail-Khan Roohi , Han Heather , Neuger Anthony , Antonia Scott , Sullivan Daniel , Soliman Hatem Hussein 
Published: March 2020

TPS2620 Background: The indoleamine 2, 3 dioxygenase pathway (IDO) can create immune suppression and unresponsiveness to tumor antigens in tumor-bearing hosts. 1-methyl-D-tryptophan (1-MT), an oral inhibitor of the IDO pathway, showed favorable toxicity profile and biologic activity in prior studies. Remarkably, in prior animal models (MMTV-neu mice), 1-MT in combination with chemotherapy produced 30% greater tumor regressions. Based on this data, a phase I trial was initiated to study the synergism of 1-MT with docetaxel. The primary goal of this trial is to determine the MTD and toxicity for the combination of docetaxel and oral 1-MT. A secondary endpoint will be to determine the PK data and the overall response rate. Methods: This phase I study utilizes a 3+3 design comprised of five dose levels. Dose levels 1-4 will evaluate docetaxel 60mg/m2 IV d1 q3wks plus 1-MT at 300mg, 600mg, 1000mg, and 2000mg PO BID d1-21 respectively. Dose level 5 is docetaxel 75mg/m2 IV d1 q3wks + 1-MT 2000mg PO BID d1-21. Eligibility for this study includes patients with measurable metastatic solid malignancy, no prior docetaxel for metastatic disease, age ≥18, life expectancy >4 months, and adequate organ/marrow function. Patients will be excluded if they meet any of the following criteria: chemotherapy within the past 3 weeks, untreated brain metastases, active autoimmune disease, or GI disease causing malabsorption. In addition, any patients who have received prior immunotherapy such as ipilimumab are excluded. Treatment will continue until disease progression, unacceptable toxicity, or patient/physician discretion. Accrual to dose level 3 is complete and dose level 4 accrual is underway. The PK of 1-MT and docetaxel will also be characterized, using an HPLC assay. PK measurements for 1-MT are drawn on C1D1 after a single dose of 1-MT is given and then on C1D8 after the morning dose of 1-MT is given. (Drawn at 0,1,2,4,8,12,24, and 48 hours) Because IDO is hypothesized to cause regulatory T cell expansion, circulating Tregs will be quantified utilizing flow cytometry for CD4+CD25+ FoxP3+ cells. (NCT01191216)
A phase I trial of riluzole and sorafenib in patients with advanced solid tumors and melanoma.
Authors: Mehnert Janice M. , Semlani Neha , Wen Yvonne , Tan Antoinette R. , Moss Rebecca Anne , Adams Shari , Stein Mark N. , Ross Mikel , Kane Michael P. , Gibbon Darlene , Wright John Joseph , Aisner Joseph , Chen Suzie , Goydos James S 
Published: March 2020

TPS3112 Background: Metabotropic glutamate receptor 1 (GRM1) has been identified as a potential therapeutic target in melanoma. Over 60% of human melanomas express this cell surface glutamate receptor and excitation of GRM1 results in the activation of MAPK and PI3K/AKT pathways. Riluzole, an oral GRM1 blocking agent, results in growth arrest of melanoma cells in vitro and in vivo. We previously reported that administration of riluzole to melanoma patients suppressed activity of the PI3K/AKT and MAPK pathways in paired tumor samples (Yip Clin Cancer Res 2009). In preclinical studies, the efficacy of riluzole was attenuated in melanoma cells harboring BRAFV600E mutations, but sorafenib, a RAF kinase inhibitor, enhanced the effect of riluzole on these cells. The combination of riluzole and sorafenib was additive or synergistic in both BRAF mutant and BRAF wildtype melanoma cells in vitro and in BRAF wildtype cells in a xenograft model (Lee HJ Clin Cancer Res 2011). We thus designed a phase I trial to test the combination of riluzole with sorafenib in patients with solid tumors and advanced melanoma. Methods: The primary objective of this trial is identification of the maximum tolerated dose (MTD). An expansion cohort at the MTD is planned for patients with advanced melanoma to examine the correlation of clinical or radiographic response with signaling through the MAPK and PI3K/AKT pathways and with GRM1 receptor status of individual tumors. Eligible patients must have advanced solid tumors (phase I) or stage III unresectable/stage IV melanoma with biopsiable tumor (expansion cohort) and ECOG PS ≤ 2. Riluzole will be administered at 100 mg twice daily combined with sorafenib beginning at 200 mg daily and escalating in subsequent cohorts at 200 mg increments. Correlative studies: Tumors will be assessed for BRAF and NRAS mutational status. Pretreatment tumor blocks will be examined for GRM1 receptor status by immunohistochemistry. Pre and post treatment levels of pERK and pAKT will be measured in paired tumor samples to assess effects of treatment on MAPK and PI3K signaling. Limited sampling pharmacokinetic studies will be performed. Progress: Accrual to three cohorts is complete without DLT. Accrual to the final planned cohort is in progress.
A randomized, phase II, multicenter, double-blind, placebo-controlled study evaluating onartuzumab (MetMAb) in combination with mFOLFOX6 plus bevacizumab in patients with metastatic colorectal cancer.
Authors: Bendell Johanna C. , Ervin Thomas J. , Gallinson David H. , Singh Jaswinder , Wallace James Alfred , Saleh Mansoor N. , Vallone Marcy , Hack Stephen Paul 
Published: March 2020

TPS3640 Background: Dysregulation of the HGF/Met (Met) pathway has been linked with poor prognosis in colorectal cancer. Crosstalk between the Met and vascular endothelial growth factor (VEGF) pathways may be important during tumorigenesis. Aberrant activation of the HGF/Met pathway may promote angiogenesis via tumor cell secretion of angiogenic factors or directly activating endothelial cells. Onartuzumab (MetMAb) is a monovalent, monoclonal antibody that specifically binds to the Met receptor. The combination of onartuzumab and VEGF inhibition in preclinical models resulted in enhanced antitumor activity over either treatment alone. Preclinical efficacy data support the combination of onartuzumab with platinum agents. In phase I studies, onartuzumab has been generally well tolerated alone and in combination with bevacizumab. Adverse events most commonly associated with onartuzumab are peripheral edema and fatigue. Methods: This is a randomized, two-arm, phase II study in patients with previously untreated metastatic colorectal cancer. Patients (n=188) will be randomized (1:1) to either mFOLFOX6/bevacizumab/placebo or mFOLFOX6/bevacizumab/onartuzumab. Oxaliplatin will be discontinued after 8 cycles with remaining drugs continued until progression. The primary endpoint of this study is PFS in all patients. PFS by Met IHC diagnostic status (Met positive vs Met negative) will also be analyzed. Secondary endpoints include OS, ORR, safety, and biomarker analyses. Primary and secondary analyses will include all randomized patients and will be conducted according to assigned treatment arm. Kaplan–Meier methodology will be used to estimate median PFS for each treatment arm. An estimate of HR with 95% CI will be determined using a Cox regression model. Safety will be assessed in all patients receiving at least one dose of any treatment. This study is open for accrual; further details can be found on ClinicalTrials.gov (NCT01418222).
ATTACHE: A phase III, multicenter, randomized comparison of chemotherapy given prior to and post surgical resection versus chemotherapy given post surgical resection for hepatic metastases from colorectal cancer.
Authors: Fawcett Jonathan , Sjoquist Katrin Marie , Padbury Rob , Christophi Christopher , Tebbutt Niall Christopher , Pilgrim Charles Henry Caldow , Gebski Val , Wong Nicole , Aiken Christine , Goldstein David ,   Australasian Gastro-Intestinal Trials Group (AGITG)
Published: March 2020

TPS3643 Background: No randomized studies have directly compared the role of peri-operative to adjuvant chemotherapy for resectable liver metastases. Benefit from post operative compared to peri-operative treatment has been suggested in a recent retrospective study of 499 patients with resected colorectal liver metastases which showed improved survival with entirely post-operative chemotherapy. Given this data and that of the small randomised trials demonstrating improved surgical outcomes with adjuvant chemotherapy, the role of entirely post-operative chemotherapy as a means of improving outcomes while reducing the negative effects of pre-operative treatment needs to be examined. Methods: 200 patients randomized 1:1 to 6 months of treatment post-operatively or 3 months of treatment pre-operatively and 3 months post-operatively. Site investigators will nominate chemotherapy schedule (mFOLFOX6, XELOX or FOLFIRI when adjuvant oxaliplatin received previously) prior to randomisation. Primary endpoint: proportion of patients in each arm with surgical complications within 30 days. Secondary endpoints: proportion of patients completing planned chemotherapy, post operative mortality rate (in each group), tolerability and safety of treatment, response rate by RECIST V1.1 and CEA, time to progression, time to treatment failure, overall survival, QoL (EORTC QLQ-C30 and QLQ-LMC21). A planned prospective meta-analysis with MRC (UK) and NSABP C-11 trials will have sufficient power to examine the effect of schedule (peri- or post-operative) on progression free survival (PFS). Eligibility: Patients with histologically proven colorectal cancer with radiologically confirmed, resectable liver metastases without evidence of extra-hepatic disease are eligible. Patients with synchronous metastases who have undergone resection of the primary tumour are eligible but patients requiring combined resection of primary cancer and liver metastatic disease are excluded. Patients with involved hilar nodes or wound implant metastases will not be eligible. Trial Status: Study opened to accrual August 2011.