bluuebunny/crossref_metadata_2025_split huggingface dataset:
CALM study: A phase II study of intratumoral coxsackievirus A21 in patients with stage IIIc and stage IV malignant melanoma.
Authors: Andtbacka Robert Hans Ingemar , Kaufman Howard , Daniels Gregory A. , Spitler Lynn E. , Lutzky Jose , Hallmeyer Sigrun , Whitman Eric D. , Nemunaitis John J. , Zhou Karl , Karpathy Roberta , Weisberg Jeffrey Ira , Shafren Darren 
Published: March 2020

TPS3128 Background: Coxsackievirus A21 (CVA21: CAVATAK) is a naturally occurring "common cold" virus. CVA21 displays potent oncolytic activity against both in vitro cultures of cancer cells and against in vivo xenografts of human cancers in mouse models of melanoma, prostate cancer, breast cancer and multiple myeloma, all which exhibit high surface ICAM-1 expression, which is used for viral entry. In mouse human melanoma xenograft CVA21 challenge models, progeny virus released from infected cells is capable of targeting adjacent cells, entering the systemic circulation, and destroying micro-metastatic foci. In a phase 1 study, two intralesional injections of CVA21 were shown to reduce or stabilize the growth of injected melanoma lesions. Methods: The CALM study investigates the efficacy and safety of intratumoral CVA21 in approximately 63 pts with treated or untreated unresectable Stage IIIC-IVM1c melanoma. Pts are treated with up to 3 x 108 TCID50 intratumorally on study days 1, 3, 5 and 8 and then every three weeks for a further 6 injections. Key eligibility criteria are ≥ 18 yrs old, ECOG 0-1, and at least 1 injectable cutaneous, sc, or nodal tumor >1.0 cm. The primary endpoint is irPFS at 6 months following tx; secondary endpoints include durable response rate and OS. A 2-stage Simon’s minimax design will be employed. Based on data from previous trials and literature, a target overall irPFS at 6 months of 22.5% versus a projected rate of 10% in the target population is selected. With an alpha level of 5% and 80% of power, a total of 54 evaluable patients will be required to test the null hypothesis that the true irPFS rate is <10% versus the alternative hypothesis that the true irPFS rate is at least 22.5%. Thirty-five patients will be treated at Stage I. If 3 or more objective responses (CR or PR) are achieved by modified RECIST 1.1 criteria in the first 35 patients, then the study will complete enrollment. Results: Currently, 21 patients have been enrolled on the study and treated with CVA21 injections. The treatment has been well tolerated. The Stage I interim efficacy endpoint of > 3 objective responses has been achieved, and the second stage of the study is proceeding with a planned enrollment of a total of 63 patients. Clinical trial information: NCT01227551.
A phase III study of the impact of a physical activity program on disease-free survival in patients with high-risk stage II or stage III colon cancer: A randomized controlled trial (NCIC CTG CO.21).
Authors: Booth Christopher M. , Courneya Kerry S. , Vardy Janette L. , Jonker Derek J. , Gill Sharlene , Brundage Michael , van der Ploeg Hidde , Dhillon Haryana M. , O'Brien Patti , Goddard Emma , Pollak Michael N. , Friedenreich Christine , Tu Dongsheng , Wong Rebecca , Meyer Ralph M. 
Published: March 2020

TPS3647 Background: Observational data indicate that physical activity (PA) is strongly associated with colon-cancer specific survival. NCIC CTG CO.21 (CHALLENGE) is designed to determine the effects of a structured PA intervention on disease-control outcomes for survivors of high-risk stage II or III colon cancer who have completed adjuvant chemotherapy within the previous 2-6 months. Methods: Phase III randomized controlled trial. Target sample size of 962 patients is powered to detect a Hazard Ratio of 0.75 for disease-free survival (DFS). Trial participants will be stratified by centre, disease stage, body mass index, and performance status, and will be randomly assigned to a structured, individualized PA intervention or to general health education materials. The PA intervention will consist of a behavioural support program and supervised PA sessions delivered over a 3-year period, beginning with regular face-to-face sessions and tapering to less frequent face-to-face or telephone sessions. The goal of the PA program is to increase weekly PA by 10 MET hours/week. The PA program is delivered by physical activity consultants trained in exercise physiology and behavior change. Outcomes: The primary endpoint is DFS. Important secondary endpoints include multiple patient-reported outcomes (including those that address fatigue), objective physical functioning, biologic correlative markers (including assessment of the insulin pathway), and an economic analysis. Current Enrollment: The study is open at 19 centers in Canada and 20 centers in Australia. Accrual as of February 4, 2013 includes 212 registered and 184 randomized patients. Summary: Cancer survivors and cancer care professionals are interested in the potential role of PA to improve multiple disease-related outcomes, but a randomized controlled trial is needed to provide compelling evidence to justify changes in health care policies and practice. Clinical trial information: NCT00819208.
Efficacy and safety of gemcitabine in combination with TH-302 compared with gemcitabine in combination with placebo in previously untreated patients with metastatic or locally advanced unresectable pancreatic adenocarcinoma: The MAESTRO trial.
Authors: Van Cutsem Eric , Fram Robert J. , Schlichting Michael , Ryan David P. 
Published: March 2020

TPS4148 Background: Tumors often consist of highly hypoxic subregions that are resistant to chemotherapy and radiotherapy. The investigational hypoxia-targeted drug TH-302 is reduced at its nitroimidazole group, and under hypoxic conditions releases the DNA alkylator bromo-isophosphoramide mustard (Br-IPM). A randomized Phase IIb trial of TH-302 in pts with metastatic or locally advanced unresectable pancreatic adenocarcinoma (PDAC) confirmed a significant PFS improvement (p=0.008) in pts treated with TH-302 at 340 mg/m2+ gemcitabine compared with gemcitabine alone (Borad et al, ESMO 2012). Skin and mucosal toxicities, mainly Grade 1/2, and myelosuppression (thrombocytopenia, neutropenia and anemia) were the most common AEs related to TH-302 and did not lead to increases in treatment discontinuation. Grade 3/4 myelosuppression was more frequent in the TH-302 + gemcitabine arm. AEs leading to treatment discontinuation as well as non-hematological serious AEs were balanced across arms. Methods: This is a Phase III, randomized, double-blind, placebo-controlled trial (NCT01746979) of gemcitabine + TH-302 compared with gemcitabine + placebo in pts with locally advanced unresectable or metastatic PDAC. The study is designed to detect a 25% risk reduction of death with 90% power and two-sided alpha of 5%. A total of 660 pts are planned to be randomized 1:1. Key eligibility criteria include histologically or cytologically confirmed disease, no prior chemotherapy or systemic therapy (except as specified in the protocol), ECOG performance status 0 – 1, and bilirubin ≤ 1.5x upper limit of normal. Randomized pts receive TH-302 + gemcitabine or gemcitabine + placebo in 4-week cycles until progressive disease, intolerable toxicity, or pt withdrawal. The primary objective is to evaluate OS. Secondary objectives include PFS, objective response, and disease control; safety and tolerability; pt-reported QoL and pain; CA 19-9 levels and PK of TH-302; exploratory pharmacogenomic markers and potential predictive biomarkers. Enrollment to the study is ongoing. Clinical trial information: NCT01746979.
Pertuzumab (P) with trastuzumab (T) and chemotherapy (CTX) in patients (pts) with HER2-positive metastatic gastric or gastroesophageal junction (GEJ) cancer: An international phase III study (JACOB).
Authors: Tabernero Josep , Hoff Paulo Marcelo , Shen Lin , Ohtsu Atsushi , Yu Ron , Eng-Wong Jennifer , Kang Yoon-Koo 
Published: March 2020

TPS4150 Background: Human epidermal growth factor receptor 2 (HER2) is overexpressed in ~20% of gastric cancers. Specific targeting of HER2 by T in combination with CTX has demonstrated significantly improved overall survival (OS) vs CTX in pts with advanced gastric or GEJ cancer (Bang Lancet 2010). In HER2-positive 1L metastatic breast cancer the combination of T plus docetaxel with a second HER2-targeted antibody, P, demonstrated significant improvement of progression-free survival (PFS) and OS vs placebo+T+docetaxel (Baselga NEJM 2012; Swain SABCS 2012). Based on these positive findings with HER2-targeted therapies in gastric and breast cancer, JACOB, a double-blind, placebo-controlled, randomized Phase III study, is designed to evaluate efficacy and safety of P+T+CTX in pts with HER2-positive 1L metastatic gastric or GEJ cancer. Methods: Pts will be randomized 1:1 to receive P+T+cisplatin+fluoropyrimidine or the same regimen replacing P with placebo, q3w (P: 840 mg; T: 8 mg/kg first dose, then 6 mg/kg; cisplatin: 80 mg/m2; 5-fluorouracil: 800 mg/m2/24 h given continuously for 120 h or capecitabine: 1000 mg/m2 bid for 14 days). P/placebo+T will be given until progressive disease (PD) or unacceptable toxicity. On or before Cycle 6, CTX should only be discontinued for PD or unacceptable toxicity. Continuation of CTX after Cycle 6 is at the discretion of pt and physician. Randomization will be stratified by region (Japan vs North America/Western Europe/Australia vs Asia [excluding Japan] vs South America/Eastern Europe), prior gastrectomy, and HER2-positivity (IHC 3+ vs IHC 2+ and ISH+). Primary endpoint: OS; secondary endpoints include PFS, objective response rate, duration of response, clinical benefit rate, safety, pharmacokinetics of P, and patient-reported outcomes. Tumor and blood samples for biomarker evaluation will be collected. The study is estimated to have 80% power to detect a significant improvement in OS at a two-sided α-level of 5% (HR=0.777), with ~502 deaths required for the primary analysis. Target enrollment is 780 pts from ~200 sites and 35 countries; FPI is planned for April 2013. NCT01774786 Clinical trial information: NCT01774786.
RILOMET-1: An international phase III multicenter, randomized, double-blind, placebo-controlled trial of rilotumumab plus epirubicin, cisplatin, and capecitabine (ECX) as first-line therapy in patients with advanced MET-positive gastric or gastroesophageal junction (G/GEJ) adenocarcinoma.
Authors: Cunningham David , Al-Batran Salah-Eddin , Davidenko Irina , Ilson David H. , Murad André M. , Tebbutt Niall C. , Jiang Yizhou , Loh Elwyn , Dubey Sarita ,   RILOMET-1 investigators
Published: March 2020

TPS4153 Background: Rilotumumab is an investigational, fully human monoclonal antibody to hepatocyte growth factor/scatter factor that inhibits signaling through the MET receptor. In a randomized phase II study in patients with advanced G/GEJ adenocarcinoma, addition of rilotumumab every 3 weeks (Q3W) to ECX showed trends toward improved overall survival (OS) and progression-free survival (PFS) compared with ECX alone. In patients with high tumor MET expression and high rilotumumab exposure, the treatment effect of rilotumumab combined with ECX was significantly enhanced. Methods: In this phase III study, patients (planned N=450) are randomized 1:1 to ECX (intravenous [IV] epirubicin 50 mg/m2 on day 1, IV cisplatin 60 mg/m2 on day 1, and oral capecitabine 625 mg/m2 twice daily on days 1−21) plus double-blind rilotumumab 15 mg/kg or placebo IV Q3W. Randomization is stratified by disease extent (locally advanced vs metastatic) and Eastern Cooperative Oncology Group (ECOG) score (0 vs 1). Key eligibility criteria include previously untreated, pathologically confirmed unresectable locally advanced or metastatic G/GEJ adenocarcinoma; ECOG score 0 or 1; ≥18 years old; MET-positive by centralized immunohistochemistry; HER2-negative; adequate organ function; and ≥6 months since neoadjuvant/adjuvant therapy. The primary endpoint is OS. Key secondary endpoints include PFS, 12-month survival rate, objective response, OS in MET expression tertiles, safety, and pharmacokinetics. An exploratory objective is to assess associations between outcomes and tumor and circulating biomarkers. Enrollment began in November 2012, and the trial continues to accrue. An independent data monitoring committee will conduct planned interim reviews for safety and efficacy. Status: recruiting participants. Sponsored by Amgen Inc. Clinical trial information: NCT01697072.
A randomized controlled trial comparing modified gemcitabine plus oxaliplatin (mGEMOX) to gemcitabine plus cisplatin in the management of unresectable gall bladder cancer.
Authors: Sharma Atul , Chaudhary Surendra Pal , Shukla N. K. , Mohanti B. K. , Deo S. V. S. , Pal Sujoy , Raina Vinod , Thulkar Sanjay , Vishnubhatla Sreenivas , Kumar Rakesh , Iyer V. K. 
Published: March 2020

TPS4162 Background: In a recently conducted study we have shown that combination of gemcitabine and oxaliplatin is superior to 5 fluorouracil and leucoverine or best supportive care. (Sharma A, Dwary AD, Mohanti BK,et al. Best supportive care compared with chemotherapy for unresectable gall bladder cancer:A randomized controlled study. J Clin Oncol. 2010; 28: 4581-4586.) In another recent publication from UK, gemcitabine and cisplatin combination was found superior to gemcitabine alone in biliary tract cancers (J W Valle, HS Wasan, DD Palmer, et al. Cisplatin plus gemcitabine versus gemcitabine for biliary tract cancer. N Eng J Med. 2010;362:1273-1281.).The current study is being planned to see whether the combination of gemcitabine and oxaliplatin is equivalent (equivalence study) to gemcitabine and cisplatin in these patients. Methods: Primary end point of the study is overall survival in subjects receiving mGEMOX or GemCis regimen. Secondary end points are: a) Comparison of progression free survival in 2 groups; b) Response rates in two groups; c) Identification of genes predictive of responses in a subset of patients; d) To evaluate role of PET CT in GBC patients predicting disease activity. Sample size was calculated taking median survival of 9.5 months in our previous study with mGEMOX and 11.7 months with GemCis. For this total of 216 patients are required (108 in each arm); to make for major protocol violation and lost to follow up additional 22 patients in each arm will be enrolled. Thus in total 260 patients (130) in each arm will be recruited. This will have alpha and beta values of 0.05 and 0.20 respectively. So far 103 patients have been enrolled and interim analysis is being planned. Treatment protocol: Cycles will be repeated every 3 weeks. Arm A- mGEMOX. Inj Oxaliplatin 80 mg/m22 hours infusion in Dextrose 5% Day 1 and 8. Inj Gemcitabine 900 mg/m2IV 30 minutes infusion day 1 and 8 maximum of 6 cycles. Arm B- GEMCIS. Inj Cisplatin 25 mg/m2PO Days 1 and 8. Inj Gemcitabine 1000 mg/m2IV 30 minutes infusion day1and 8 maximum of 8 cycles. Clinical trial information: CTRI/2010/091/001406.
Phase III randomized sequential open-label study to evaluate the efficacy and safety of sorafenib followed by pazopanib versus pazopanib followed by sorafenib in the treatment of advanced/metastatic renal cell carcinoma (SWITCH-2 study).
Authors: Gschwend Juergen , Beeker Aart , de Santis Maria , Brehmer Bernhard , Zaiss Matthias R. , Schirrmacher-Memmel Silke , Von Verschuer Ulla , Bos Monique M.E.M. , Pahernik Sascha , Grimm Marc-Oliver , Krause Steffen , Retz Margitta 
Published: March 2020

TPS4591 Background: Sorafenib (SO) and pazopanib (PA) are both effective treatments for metastatic RCC (mRCC). For optimal treatment of mRCC patients (pts) it is essential to compare efficacy and safety of different sequential 1st and 2nd line treatments. The primary endpoint of this study is to evaluate if total PFS of SO followed by PA is non-inferior to PA followed by SO. Secondary objectives include time to progression during second-line treatment; time to first-line treatment failure in each arm, and PFS in first- and second-line treatment; overall survival; disease control rate in first- and second-line, safety and tolerability, and health-related quality of life. Also, a comprehensive translational research programme is integrated. Methods: Major inclusion criteria: pts with metastatic/advanced RCC not suitable for cytokines and for whom study medication constitutes first-line therapy; 18-85 years, ECOG PS 0 or 1, MSKCC score low or intermediate; at least one measurable lesion (RECIST 1.1). 544 pts will be randomized to the sequence SO→PA or PA→SO. Treatment under each drug continues until progression or intolerable toxicity. Between 1st and 2ndline therapy will be a treatment-free period of 1-4 wks. SO and PA are given in their registered doses. Pts undergo CT/MRI after every second cycle, i.e. after every 8 wks. The experimental arm will be considered to be non-inferior as long as the lower limit of the HR 95 % confidence interval (one-sided) excludes a median total PFS lower than 13.1 mos (=non inferiority margin). 383 events need to be observed to have 80% power to reject the null hypothesis of inferiority (HR ≥1.225) when the true HR=0.95. Recruitment started in June 2012. Study centers are in Germany, The Netherlands, and Austria. Clinical trial information: NCT01613846.
CA184-095: A randomized, double-blind, phase III trial to compare the efficacy of ipilimumab (Ipi) versus placebo in asymptomatic or minimally symptomatic patients (pts) with metastatic chemotherapy-naive castration-resistant prostate cancer (CRPC).
Authors: Beer Tomasz M. , Logothetis Christopher , Sharma Padmanee , Loriot Yohann , Fizazi Karim , Bossi Alberto , Kwon Eugene D. , McHenry Brent , Gagnier Paul , Gerritsen Winald R. 
Published: March 2020

TPS5093 Background: Globally, docetaxel remains the standard of care for metastatic CRPC; however, its use may be delayed until pts develop symptoms. The presence of infiltrating leukocytes in CRPC tumors suggests a natural antitumor immune response is occurring. This is supported by an overall survival (OS) benefit reported in men with asymptomatic or minimally symptomatic metastatic CRPC who received sipuleucel-T. Ipi, a monoclonal antibody that binds CTLA-4, augments antitumoral activity of cytotoxic immune cells. Ipi demonstrated OS benefit in two phase III trials for advanced melanoma, with side effects that were managed using product-specific treatment guidelines. In phase I/II trials in metastatic CRPC, Ipi has shown clinical activity (as measured by prostate-specific antigen [PSA] declines and RECIST response) with a similar toxicity profile to that observed in melanoma. This global (149 sites in 24 countries) phase III study (ClinicalTrials.gov identifier: NCT01057810) evaluates Ipi vs placebo in chemotherapy-naïve pts with asymptomatic or minimally symptomatic CRPC without visceral metastases. Methods: The primary endpoint is OS; secondary endpoints include progression-free survival, time to pain progression, time to non-hormonal systemic therapy and safety characterization. The study is designed to detect a 9.3-month median difference (HR=0.7) in OS with 90% power and 0.05 two-sided significance. Pts are randomized at a 2:1 ratio to receive Ipi 10 mg/kg every 3 weeks for up to 4 doses or placebo as induction therapy. Eligible pts will receive maintenance therapy of blinded study drug every 12 weeks. The accrual goal is 600 pts randomized. Clinical trial information: NCT01057810. [Table: see text] [Table: see text]
Randomized double-blind, comparative study of abiraterone acetate (AA) plus low-dose prednisone (P) plus androgen deprivation therapy (ADT) versus ADT alone in newly diagnosed, high-risk, metastatic hormone-naive prostate cancer (mHNPC).
Authors: Fizazi Karim , Larsen Julie S. , Matheny Shannon , Molina Arturo , Li Jinhui , Todd Mary Beth , Yu Margaret K. , Kheoh Thian San , Tran Namphuong 
Published: March 2020

TPS5097 Background: Patients (pts) who initially present with metastatic prostate cancer (MPC) (up to 30% of men in Europe; 4% in US) typically progress to metastatic castration-resistant prostate cancer (mCRPC) with a poor prognosis. Prognostic factors impacting survival include high PSA concentration, high Gleason score, high volume of metastatic disease, and bone symptoms. AA decreases testosterone via CYP17 inhibition and is approved for treatment of mCRPC before and after docetaxel-based chemotherapy. Two recent reports (J Clin Oncol. 2012: 30 [suppl. abstr 4521 and 4556]) showed that AA + P in addition to ADT (LHRH agonist) in the neoadjuvant setting led to higher rates of undetectable PSA and complete pathologic response (cPR) or near-cPR in pts undergoing prostatectomy for high risk-localized prostate cancer than with ADT alone, suggesting a potential role for inhibiting extragonadal androgen synthesis prior to emergence of castration-resistance. Because of its benefit in mCRPC, as well as early activity in high risk-localized prostate cancer, AA is being evaluated in high risk mHNPC. Methods: Approximately 1,270 men with newly diagnosed (within 3 months of randomization) high risk mHNPC with at least 2 of 3 high risk factors (≥ 3 bone lesions, presence of visceral metastases or Gleason score ≥ 8) are being randomized to AA 1000 mg + P 5 mg daily + ADT or ADT alone. Pts are stratified by presence of visceral disease and ECOG PS (0-1 vs 2). Distant metastatic disease must be documented by positive bone scan or CT/MRI. ADT or orchiectomy within 3 mos of randomization is allowed. Continued use of anti-androgens after randomization is not allowed on study. The primary endpoint is overall survival. Secondary endpoints include radiographic PFS, time to next skeletal-related event, PSA progression, and subsequent therapy. Two interim analyses and a final analysis are planned. 300 sites from 36 countries will participate. As of February 4, 2013, one patient has entered screening. Clinical trial information: NCT01715285.