Voghera (pavia), Italy
Study of Perioperative Dostarlimab in Participants With Untreated T4N0 or Stage III dMMR/MSI-H Resectable Colon Cancer
Phase
3Span
387 weeksSponsor
GlaxoSmithKlineMonserrato, Sardegna
Recruiting
Taletrectinib Phase 2 Global Study in ROS1 Positive NSCLC
This is a global Phase 2, multicenter, single-arm, open label study of taletrectinib in patients of NSCLC harboring with ROS1 fusion gene. About 224 patients will be enrolled and divided into 6 cohorts, depending on past history of ROS1 TKI treatment. In the cohorts open to enrollment, taletrectinib will be administered either 400mg or 600mg once daily in 21-day cycles. In one cohort, this will be in combination with carboplatin and pemetrexed both administered by IV infusion in 21-day cycles for 4 cycles. Patients will continue with the treatment on taletrectinib until progression of disease as determined by the investigator. The tumor response evaluation will be conducted on a regular basis until progression of disease. Long-term survival follow up will be conducted as well.
Phase
2Span
304 weeksSponsor
Nuvation Bio Inc.Monserrato
Recruiting
Healthy Volunteers
Axitinib Intensification Plus Nivolumab or Nivolumab Alone After Nivolumab Plus Ipilimumab in mRCC Patients
The present study aims to demonstrate if the addition of axitinib to nivolumab maintenance after nivolumab plus ipilimumab induction can improve the rate of response considering that the incidence of partial response was 32% and 51% in Checkmate214 and Keynote426 trials respectively. This study requires 106 patients to show an improvement from 30% to 50% of the incidence of partial responses with a power of 80%, and alpha-error 0.10 (one-side p). Assuming a drop out of 10%, the final estimated number to enroll should be 118 (59 in arm A and 59 in arm B).
Phase
2Span
207 weeksSponsor
Consorzio OncotechMonserrato
Recruiting
A Phase II Randomized, Open Label Non-inferiority Study of NiraParib Maintenance After 3 vs. 6 Cycles of Platinum-based Chemotherapy in completeLy debUlked Advanced HRDpositive High-grade Ovarian Cancer patientS in First Line Therapy
This is a multicenter, randomized, open label study including patients with advanced (FIGO stage IIIA, IIIB, IIIC, or IV of the 2014 FIGO classification) HRDpositive high-grade ovarian cancer, fallopian tube cancer, primary peritoneal cancer and clear cell carcinoma of the ovary with no residual tumor mass following primary tumor debulking. The main scope of the trial is to determine recurrence free survival in patients treated with 3 cycles carboplatin + paclitaxel and maintenance therapy with niraparib vs. 6 cycles carboplatin + paclitaxel and maintenance therapy with niraparib. Patients will be randomized 1:1 to receive either 3 cycles carboplatin + paclitaxel maintenance therapy with niraparib (Arm A) or 6 cycles carboplatin + paclitaxel and maintenance therapy with niraparib (Arm B). Randomization will be performed according to the results of the NGS analysis and stratified either to BRCAm independent of LOH or LOHhigh/ BRCAwt, FIGO stage III vs. IV, and countries. In both of the arms, tumor assessments (CT or MRI) will be performed 9-12 weeks after the start of therapy (after 3rd cycle of chemotherapy), after another 9-12 weeks (during maintenance therapy in Arm A and after the 6th cycle of chemotherapy in Arm B) and every 6 months thereafter. The tumor marker CA-125 will be assessed every 12 weeks in both arms. During chemotherapy treatment, clinical visits (blood cell counts, detection of toxicity) occur at least every 3 weeks (depending on the chemotherapy regimen). Serum pregnancy tests for WOCBP occur at least every 4 weeks. During maintenance therapy with niraparib, clinical visits (blood cell counts, detection of toxicity) occur every 4 weeks for the first 11 months and every 12 weeks thereafter. Serum pregnancy tests for WOCBP occur at least every 4 weeks. Complete physical examinations will take place every 12 weeks. Safety will be monitored continuously by careful monitoring of all adverse events (AEs) and serious adverse events (SAEs). About 60 sites in 6 European countries will participate in this study to recruit 640 patients in 36 months.
Phase
2Span
416 weeksSponsor
North Eastern German Society of Gynaecological OncologyMonserrato
Recruiting
Savolitinib Plus Osimertinib Versus Platinum-based Doublet Chemotherapy in Participants With Non-Small Cell Lung Cancer Who Have Progressed on Osimertinib Treatment
This is a multicentre, Phase III, randomised, open-label study to investigate the efficacy and safety of savolitinib administered orally in combination with osimertinib versus platinum-based doublet chemotherapy in participants with EGFR mutated, MET-overexpressed and/or amplified, locally advanced or metastatic NSCLC who have progressed on first- or second-line treatment with osimertinib as the most recent therapy. Approximately 324 participants with EGFR mutated, MET-overexpressed and/or amplified, locally advanced or metastatic NSCLC will be randomly assigned to study intervention with 1:1 ratio. Patients will be treated until either objective progression of disease (PD) by Response Evaluation Criteria in Solid Tumours 1.1 (RECIST 1.1) is assessed by the investigator, unacceptable toxicity occurs, consent is withdrawn, or another discontinuation criterion is met.
Phase
3Span
229 weeksSponsor
AstraZenecaMonserrato
Recruiting
Behçet's Disease Overall Damage Index
DESIGN OF THE STUDY This observational multicenter study will be developed in 2 subsequent phases, in their turn, consisting of different steps (figure 1): 1. BODI Development 1.1) Development of a preliminary version of BODI (p-BODI) based on literature review and inspired by pre-existing tools according to OMERACT guidelines; 1.2) Delphi process aimed to review and improve the p-BODI. 2. Validation of the new tool according to OMERACT filter 2.0 2.1) Application of the BODI on a multicentre cohort of BD patients. 2.2) Assessment of face, content, construct and criterion validity, and sensitivity to change. 2.3) Assessment of reliability based on scoring exercise on clinical vignettes. All subjects involved in the study are experts in the management of BD. They will work in two different groups having different roles: - Work and facilitator group (WFG): consisting of 3 Physician from the Coordinating Centre. The tasks of the WFG are: (a) to review literature and develop a preliminary version of BODI (p-BODI), including: definition of damage, rules for scoring and identification of potential items of damage; (b) to coordinate the Delphi process for editing and optimizing p-BODI; (c) to analyse data from the validation process. - Expert Panel (EP): consisting of multidisciplinary experts in Behçet's disease and Patient's delegate from different countries. EP members will be selected and invited to participate in the study by the WFG. The tasks of the EP are to express their opinion on p-BODI and propose editing for its improvement within a Delphi process; - Clinicians group (CG): consisting of one Clinician from each Centre, with expertise in Behçet's disease but not involved in the Delphi process. The tasks of this group are: (a) to apply the BODI on 30 consecutive patients with BD (10 for Neurologist and Ophthalmologist) from each Centre involved in the study; (b) to score a set of clinical vignettes using the BODI, to assess reliability of the instrument; (c) to express an overall judgement (in an online survey) regarding to general credibility, comprehensiveness and feasibility of the BODI. The member of EP and GC, involved in the study so far, with respective affiliations, are reported below: EP members - CG members - Affiliations. - Prof. Alessandro Mathieu - Dr. Matteo Piga - Chair and Unit of Rheumatology, University and AOU of Cagliari, Monserrato - Italy; - Prof. Govoni Marcello - Dr. Lo Monaco Andrea - Department of Medical Sciences, Section of Rheumatology, AOU S. Anna, the University of Ferrara - Italy; - Prof. Iannone Florenzo - Dr. Lopalco Giuseppe - Department of Emergency and Organ Transplantation, Rheumatology Unit, University of Bari - Italy; - Prof. Neri Piergiorgio - Dr. Pirani Vittorio - Ocular Immunology Service, the Eye Clinic, Polytechnic University of Marche- Ancona - Italy; - Prof. Cantarini Luca - Dr. Orlando Ida - Rheumatology Unit, University of Siena. Policlinico Le Scotte; - Prof. Martins Silva Ana - Dr. Santos Ernestina - Neurology Department, Hospital Santo António, Centro Hospitalar do Porto - Portugal; - Prof. Vasconcelos Carlos - Prof Correia Joao; Dr. Raquel Faria - Clinical Immunology Unit, Centro Hospitalar do Porto and UMIB, ICBAS, Universidade do Porto, Portugal; - Prof. Cervera Ricard - Dr. Espinosa Gerard, Dr. Ignasi Rodriguez - Department of Autoimmune Diseases, Hospital Clinic, IDIBAPS, University of Barcelona - Spain; - Prof. Bertsias George - Dr. Nikos Kougkas - Department of Rheumatology, Clinical Immunology and Allergy, University of Crete School of Medicine - Grece; - Patient Association delegates. OPERATIVE STUDY DEVELOPMENT AND DATA ANALYSIS 1. BODI Development 1.1) Development of preliminary version of BODI (p-BODI) based on literature review and inspired to pre-existing tools A preliminary list of damaged items with respective definition will be generated after reviewing the literature and preexisting damage indices (e.g VDI for vasculitides and SLICC damage index (SDI) for systemic lupus erythematosus). 1.2) Reviewing and editing of the p-BODI by Delphi process A multi-step Delphi process, based on reaching experts consensus, will be performed in order to review and refine the p-BODI and the respective glossary. Through an online survey, each member EP will be asked to rate: (a) how strongly they agree with the general rules for damage scoring; (b) how strongly they agree to include the listed damage items within the BODI (e.g. to which extent do you agree that "Cataract" should be included in the BODI?); (c) how strongly they agree with the provided item definition. Ratings will be scored on a 5-point Likert scale (5 = strongly agree; 4 = agree; 3 = unsure; 2 = disagree; 1 = strongly disagree). The EP members will be asked to give considerations and arguments to support their opinion, especially if they score less than 4. They will also be given the opportunity to suggest alternative wordings, to suggest additional items, or to make any other comment. In the reviewed p-BODI for the subsequent Delphi round, each issue (scoring rules, damage items, item definitions) if: (a) ≥80% of EP members scores ≥4: will be included; (b) 50-79% of EP members scores ≥4: will be included in the second questionnaire after reviewing according to comments and suggestions provided in the previous round (c) <50% of EP members scores: will be excluded. The WFG has the right to make alternative decisions after reviewing the EP responses (e.g propose to change an item definition according to a suggestion from the expert panel, even if the item was scored >4 by ≥80% of EP). An anonymous feedback report will be provided with the second questionnaire, in order to offer the opportunity to reconsider and, if appropriate, to change a previous opinion in light of the anonymous responses and considerations of the other EP members. The panel members will again be asked to give their opinion on each issue in subsequent rounds until complete consensus will be achieved (all issues scored ≥4 by ≥80% of EP) and the definitive version of BODI will be developed. 2. Validation of BODI 2.1) Application of BODI on a multi-center cohort of BD patients Each CG member will be asked to apply the reviewed version of BODI on a cohort of 30 BD patients consecutively assessed in their own center. For Neurologist and Ophthalmologist, the data from 10 consecutive patients will be enough. This is because Neurologist and Ophthalmologist usually take care of the most severe neuropsychiatric and ocular cases, which might bias the real prevalence of these manifestations in the study cohort. A multicenter cohort consisting of 200-250 BD patients will be thus set up. Patients will undergo a routine clinical assessment, as scheduled in their follow-up program. No further clinical, laboratory or instrumental investigations will be performed in addition to those provided according to the good clinical practice. Any possible drug administration will be evaluated independently from the study and according to the good clinical practice. Inclusion criteria will be: a) BD diagnosis according to ICBD criteria, b) disease duration ≥12 months), c) age at enrolment ≥ 18 years. For each recruited patient data will be anonymously collected at the enrolment visit (T0). For patients with more than 5 years of follow-up at the enrollment time, investigators will be further asked to perform a 5 years retrospective BODI (Tr5). The following data will be collected (see the attached Case Report Form): - T1: demographics and medical history (gender; birthday, onset, diagnosis and enrolment date; country of origin; ethnicity; comorbidity; smoker status); cumulative clinical manifestation from onset to enrolment (oral aphthosis, genital aphthosis, skin lesions, ocular involvement, neurologic lesions, vascular lesions, pathergy test, arthritis, gastrointestinal manifestations); active clinical manifestations the enrolment visit; ongoing and past therapy; BD current activity form (BDCAF); BODI; VDI; Physician global assessment (PGA)on visual analogic scale; Patients global assessment (PtGA) on visual analogic scale; Short Form 36 (SF-36) Health Survey, • Tr5 (retrospectively): BODI 2.2) Assessment of face, content, construct, criterion validity and sensitivity to change Validation will be performed according to the principles of OMERACT Filter 2.0, thus according to the criteria of (A) truth, (B) discrimination and (C) feasibility will be assessed. A.1. Face validity. Since BODI will be developed through literature review and consensus between an expert in BD management, face validity criteria should be automatically met. However, face validity will be further tested by asking each CG member to complete a questionnaire investigating the suitability of the tool. A.2. Content validity. To assure content validity, the presence of damage identified by CG but not classifiable in BODI will be assessed. Content validity will be further tested by asking each CG member to complete a questionnaire relating to the comprehensiveness of the instrument. A.3. Construct validity. It will be assessed analyzing the agreement between results of damage assessment on our validation cohort by BODI and other damage assessment tool. Since there are no other specific and validate instruments for damage amassment in Behçet disease, SLICC and VDI will be used as a surrogate. Correlation between the different indices results will be evaluated by Pearson's or Spearman's correlation coefficients. A.4. Criterion Validity. Criterion validity represents the correlation with results of measurement with the new tool and other long-term outcomes related to the phenomenon we are measuring. Since we expect that damage correlates with quality of life, disability and mortality, a correlation between BODI score and SF-36, HAQ and in the future also with mortality rate will be assessed. B.1. Reliability. Clinical vignettes will be created from real cases to test the reliability of the BODI. Thus, inter-observer agreement (kappa) will be assessed by asking a physician from every center to assess the same clinical vignettes. B.2. Sensitivity to change. The ability of the BODI to record the accumulation of damage over time will be examined by determining the change in BODI score over 5 years of follow-up on the validation cohort. The average increase of BODI score from T1 to T2 will be calculated and will be tested by the Mann-Whitney test. C. Feasibility. To test feasibility each CG member will be asked to complete a questionnaire relating to the ease of use, consumption of time and interpretability of the instrument.
Phase
N/ASpan
126 weeksSponsor
University of CagliariMonserrato
Recruiting
A Study of Guselkumab Administered Subcutaneously in Bio-naive Participants With Active Psoriatic Arthritis Axial Disease
PsA is a chronic inflammatory musculoskeletal disease that has 6 disease domains, and axial disease represents one of the domains. Guselkumab is a fully human immunoglobulin (Ig) G1 lambda monoclonal antibody (mAb) that by binding to the p19 protein subunit of interleukin (IL)-23, blocks the binding of extracellular IL-23 to the cell surface IL-23 receptor, inhibiting IL-23-mediated intracellular signaling, activation, and cytokine production. This study will consist of a screening phase (up to 6 weeks), a treatment phase (up to 48 weeks, including a placebo-controlled period from Week 0 to Week 24 and an active-controlled treatment phase from Week 24 to Week 48), and a safety follow-up phase (up to Week 60). The efficacy assessments will include assessment such as Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) score and the safety assessments will include evaluations of physical examinations, vital signs, electrocardiograms, clinical laboratory tests, and adverse events. The overall duration of the study will be up to 14 months.
Phase
4Span
272 weeksSponsor
Janssen Research & Development, LLCMonserrato
Recruiting
Determine Effectiveness of Anifrolumab In SYstemic Sclerosis (DAISY)
This is a multicenter, randomized, double-blind, placebo-controlled, Phase III study to evaluate the efficacy and safety of anifrolumab in the treatment of adult participants with Systemic Sclerosis (SSc) who may be taking one or a combination of protocol-specified standard therapies. The use of one of the following standard immunosuppressant therapies is permitted at a stable dose, but not mandated: hydroxychloroquine, mycophenolate mofetil (MMF), mycophenolic acid or mycophenolate sodium (MPA/MPS), methotrexate, azathioprine, tacrolimus, and oral glucocorticoids. MMF or MPA/MPS, azathioprine, and methotrexate may be used in combination with hydroxychloroquine and/or low-dose oral glucocorticoids [≤ 10 mg/day]. Approximately 306 eligible participants will be randomized in a 1:1 ratio to receive either anifrolumab (or matching placebo) given subcutaneously once weekly for 52 weeks. The study will be stratified by the following factors: - Interstitial lung disease (ILD) (yes, no) at Week 0 (Day1); - MMF or MPA/MPS use (yes ,no) at Week 0 (Day 1); and - Disease duration, defined as the time from the first non-Raynaud's symptom attributable to SSc (<18 months, ≥ 18 months) at Week 0 (Day 1) Study treatment will be administered subcutaneously via an accessorized prefilled syringe by study staff or by the participant or carer, either in the clinic or at home, with most doses being administered at home. The study consists of 4 periods: a 6-week screening period, a 52-week, double-blind, placebo-controlled period, a 52-week open-label active treatment period, and a 12-week safety follow-up period. There are a total of 16 study visits with most visits in the treatment period occurring every 8 to 12 weeks. The periods are described below: - Screening Period: This may involve one or more visits to the study site. - Double Blind Treatment Period: Treatment Period when participants will receive once weekly injections of anifrolumab or matching placebo. Participation will involve in-clinic study visits at Weeks 0 (Day 1), 1, 4, 8*, 16, 24, 36, 48 and 52. *The visit at Week 8 may be either by telephone or in person. - Open Label Treatment Period: At Week 52, all participants will be given anifrolumab (subcutaneous) once weekly for 52 weeks (last dose at Week 103). Participation will involve in-clinic study visits at Weeks 52, 53*, 56, 64, 76. 88 and 104. *The visit at Week 53 may be either by telephone or in person. - Safety Follow-up Period: All participants will return to the clinic for a 12-week post treatment visit. This will occur post Double Blind Treatment Period (Week 52 or Double Blind Period early discontinuation) or post Open Label Treatment Period (Week 104 or Open Label Period early discontinuation).
Phase
3Span
217 weeksSponsor
AstraZenecaMonserrato
Recruiting
A Study of Trastuzumab DeRuxtecan for Patients With Advanced HER2-pOsitive GaStric or GastroesoPhageal Junction AdEnocarcinoma Who Have Received a PrIor Trastuzumab-based Regimen Accompanied by a Disease RegistrY of Patients Treated With Conventional Therapies (PROSPERITY)
This non-interventional study will investigate the effectiveness of T-DXd, the patients demographic and clinical characteristics, treatment patterns including prophylactic medications and interventions for reduction of serious adverse events (SAEs), serious adverse drug reactions (ADRs) and safety event of interest (SEIs), tolerability, and patient survey of T-DXd, in cases with advanced HER2-positive gastric or GEJ adenocarcinoma receiving T-DXd as second line of treatment and beyond treatment option. Patients will be treated according to the proposed indication statement in the Summary of Product Characteristics (SmPC). No investigational drug will be administered in this study. Data on conventional therapy (including platinum-fluoropyrimidine doublet chemotherapy, nivolumab, ramucirumab-paclitaxel, ramucirumab monotherapy, taxane or irinotecan, and pembrolizumab monotherapy) will also be collected in a disease registry part of the study.
Phase
N/ASpan
196 weeksSponsor
Daiichi Sankyo Europe, GmbH, a Daiichi Sankyo CompanyMonserrato
Recruiting
A Study of the Efficacy and Safety of Belimumab in Adults With Systemic Sclerosis Associated Interstitial Lung Disease
Phase
2/3Span
200 weeksSponsor
GlaxoSmithKlineMonserrato, Sardegna
Recruiting