scholarly journals 694TiP DASL-HiCaP: Darolutamide augments standard therapy for localised very high-risk cancer of the prostate (ANZUP1801). A randomised phase III double-blind, placebo-controlled trial of adding darolutamide to androgen deprivation therapy and definitive or salvage radiation

2020 ◽  
Vol 31 ◽  
pp. S548-S549
Author(s):  
T. Niazi ◽  
S. Williams ◽  
I.D. Davis ◽  
M.R. Stockler ◽  
A. Martin ◽  
...  
Keyword(s):  
High Risk ◽  
Androgen Deprivation Therapy ◽  
Standard Therapy ◽  
Controlled Trial ◽  
Phase Iii ◽  
Double Blind ◽  
Double Blind Placebo ◽  
Cancer Of The Prostate ◽  
High Risk Cancer ◽  
Very High

The Oral Neurokinin-1 Antagonist Aprepitant for the Prevention of Chemotherapy-Induced Nausea and Vomiting: A Multinational, Randomized, Double-Blind, Placebo-Controlled Trial in Patients Receiving High-Dose Cisplatin—The Aprepitant Protocol 052 Study Group

2003 ◽  
Vol 21 (22) ◽  
pp. 4112-4119 ◽  
Author(s):  
Paul J. Hesketh ◽  
Steven M. Grunberg ◽  
Richard J. Gralla ◽  
David G. Warr ◽  
Fausto Roila ◽  
...  
Keyword(s):  
Standard Therapy ◽  
Therapy Group ◽  
Rescue Therapy ◽  
Controlled Trial ◽  
Complete Response ◽  
Nausea And Vomiting ◽  
Phase Iii ◽  
High Dose ◽  
Double Blind ◽  
Double Blind Placebo

Purpose: In early clinical trials with patients receiving highly emetogenic chemotherapy, the neurokinin antagonist aprepitant significantly enhanced the efficacy of a standard antiemetic regimen consisting of a type-three 5-hydroxytryptamine antagonist and a corticosteroid. This multicenter, randomized, double-blind, placebo-controlled phase III study was performed to establish definitively the superiority of the aprepitant regimen versus standard therapy in the prevention of chemotherapy-induced nausea and vomiting (CINV). Patients and Methods: Patients receiving cisplatin ≥ 70 mg/m2 for the first time were given either standard therapy (ondansetron and dexamethasone on day 1; dexamethasone on days 2 to 4) or an aprepitant regimen (aprepitant plus ondansetron and dexamethasone on day 1; aprepitant and dexamethasone on days 2 to 3; dexamethasone on day 4). Patients recorded nausea and vomiting episodes in a diary. The primary end point was complete response (no emesis and no rescue therapy) on days 1 to 5 postcisplatin, analyzed by a modified intent-to-treat approach. Treatment comparisons were made using logistic regression models. Tolerability was assessed by reported adverse events and physical and laboratory assessments. Results: The percentage of patients with complete response on days 1 to 5 was significantly higher in the aprepitant group (72.7% [n = 260] v 52.3% in the standard therapy group [n = 260]), as were the percentages on day 1, and especially on days 2 to 5 (P < .001 for all three comparisons). Conclusion: Compared with standard dual therapy, addition of aprepitant was generally well tolerated and provided consistently superior protection against CINV in patients receiving highly emetogenic cisplatin-based chemotherapy.

DASL-HiCAP (ANZUP1801): The impact of darolutamide on standard therapy for localized very high-risk cancer of the prostate—A randomized phase III double-blind, placebo-controlled trial of adding darolutamide to androgen deprivation therapy and definitive or salvage radiation in very high-risk, clinically localized prostate cancer.

2020 ◽  
Vol 38 (6_suppl) ◽  
pp. TPS385-TPS385
Author(s):  
Tamim Niazi ◽  
Scott Williams ◽  
Ian D. Davis ◽  
Martin R. Stockler ◽  
Andrew James Martin ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
High Risk ◽  
Androgen Deprivation Therapy ◽  
Androgen Deprivation ◽  
Phase Iii ◽  
Double Blind ◽  
Free Survival ◽  
One Year ◽  
The Impact ◽  
Very High

TPS385 Background: Radiation therapy (RT), plus androgen deprivation therapy (ADT) with a luteinising hormone releasing hormone analogue (LHRHA) for at least one year, is standard of care for men with very high-risk localised prostate cancer (PC), or with very high-risk features and persistent PSA after radical prostatectomy (RP). Despite this, incurable distant metastases develop within 5 years in 15% of men with very high risk features. Darolutamide is an androgen receptor antagonist with favourable tolerability. Our aim is to determine the efficacy of adding darolutamide to ADT and RT given in the setting of either primary definitive therapy (RP or RT), or adjuvant therapy for very high-risk PC. Methods: This study is a randomised (1:1) phase III placebo-controlled, double-blind trial for men planned for RT who have very high-risk localised PC, or very high-risk features with PSA persistence or rise within one year following RP. The trial will be stratified by: use of adjuvant docetaxel; pelvic nodal involvement; RP. 1100 participants will be randomised to darolutamide 600 mg or placebo twice daily for 96 weeks. Participants will receive LHRHA for 96 weeks, plus RT starting week 8-24 from randomisation. Participants are allowed nonsteroidal antiandrogen (up to 90 days) in addition to LHRHA up until randomisation. Early treatment with 6 cycles of docetaxel completed at least 4 weeks prior to RT is permitted. The primary endpoint is metastasis-free survival, with secondary endpoints overall survival, PC-specific survival, PSA-progression free survival, time to subsequent hormonal therapy, time to castration-resistance, frequency and severity of adverse events, health related quality of life, fear of recurrence. Tertiary endpoints include incremental cost-effectiveness, and identification of prognostic and/or predictive biomarkers of treatment response, safety and resistance to study treatment. Clinical trial information: NCT04136353.

DASL-HiCaP: Darolutamide augments standard therapy for localized very high-risk cancer of the prostate (ANZUP1801)—A randomized phase III double-blind, placebo-controlled trial of adding darolutamide to androgen deprivation therapy and definitive or salvage radiation.

2021 ◽  
Vol 39 (6_suppl) ◽  
pp. TPS266-TPS266
Author(s):  
Tamim Niazi ◽  
Scott Williams ◽  
Ian D. Davis ◽  
Martin R. Stockler ◽  
Andrew James Martin ◽  
...  
Keyword(s):  
High Risk ◽  
Androgen Deprivation Therapy ◽  
Background Radiation ◽  
Predictive Biomarkers ◽  
Androgen Deprivation ◽  
Phase Iii ◽  
Double Blind ◽  
Free Survival ◽  
Definitive Therapy ◽  
Very High

TPS266 Background: Radiation therapy (RT), plus androgen deprivation therapy (ADT) with a luteinizing hormone releasing hormone analogue (LHRHA), is standard of care for men with very high-risk localized prostate cancer (PC), or with very high- risk features and persistent PSA after radical prostatectomy (RP). Despite this, incurable distant metastases develop within 5 years in 15% of men with very high-risk features. Darolutamide is a structurally distinct oral androgen receptor antagonist with low blood-brain-barrier penetration, a demonstrated favorable safety profile and low potential for drug-drug interactions. Our aim is to determine the efficacy of adding darolutamide to ADT and RT in the setting of either primary definitive therapy, or adjuvant therapy for very high-risk PC. Methods: This study is a randomized (1:1) phase III placebo-controlled, double-blind trial for men planned for RT who have very high-risk localized PC; or very high-risk features with PSA persistence or rise within one year following RP. The trial will be stratified by: RP; use of adjuvant docetaxel; pelvic nodal involvement. 1100 participants will be randomized to darolutamide 600 mg or placebo twice daily for 96 weeks. Participants will receive LHRHA for 96 weeks, plus RT starting week 8-24 from randomisation. Participants are allowed nonsteroidal antiandrogen (up to 90 days) in addition to LHRHA up until randomisation. Early treatment with up to 6 cycles of docetaxel completed at least 4 weeks prior to RT is permitted. The primary endpoint is metastasis-free survival (ICECaP-validated), with secondary endpoints overall survival, PC-specific survival, PSA-progression free survival, time to subsequent hormonal therapy, time to castration-resistance, frequency and severity of adverse events, health related quality of life, fear of recurrence. Tertiary endpoints include incremental cost-effectiveness, and identification of prognostic and/or predictive biomarkers of treatment response, safety and resistance to study treatment. Clinical trial information: NCT04136353.

scholarly journals Evaluating the efficacy of a multistrain probiotic supplementation for prevention of neonatal sepsis in 0–2-month-old low birth weight infants in India—the “ProSPoNS” Study protocol for a phase III, multicentric, randomized, double-blind, placebo-controlled trial

Trials ◽  
2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Anju Pradhan Sinha ◽  
◽  
Subodh S. Gupta ◽  
Ramesh Poluru ◽  
Abhishek V. Raut ◽  
...  
Keyword(s):  
Birth Weight ◽  
High Risk ◽  
Low Birth Weight ◽  
Research Ethics ◽  
Neonatal Sepsis ◽  
Phase Iii ◽  
Low Birth Weight Infants ◽  
Probiotic Supplementation ◽  
Double Blind ◽  
Double Blind Placebo

Abstract Background Progress has been made in the reduction of under-five mortality in India; however, neonatal mortality is reducing at a slower rate. Efforts are required to bring down neonatal mortality in order to attain the Sustainable Development Goal-3. Prevention of sepsis among the high-risk, vulnerable low birth weight neonates by a newer intervention with probiotic supplementation is promising. Methods A phase III, multicenter, randomized, double-blind, placebo-controlled study is being conducted at six sites in India. A total of 6144 healthy low birth weight (LBW) infants fulfilling the eligibility criteria would be enrolled within the first week of life, after obtaining written informed consent from the parents of the infant. Randomization in 1:1 ratio, stratified by site, sex, and birth weight, would be done through an interactive web response system (IWRS) using a standard web browser and email service. Vivomixx®, a probiotic containing a mix of 8 strains of bacteria, in a suspension form standardized to deliver 10 billion CFU/ml, or an organoleptically similar placebo would be fed to enrolled infants in a 1-ml/day dose for 30 days. The follow-up of enrolled infants for 60 days would take place as per a pre-specified schedule for recording morbidities and outcome assessments at the six participating sites. Screening for morbidities would be conducted by trained field workers in the community, and sick infants would be referred to designated clinics/hospitals. A physician would examine the referred infants presenting with complaints and clinical signs, and blood samples would be collected from sick infants for diagnosis of neonatal sepsis by performing sepsis screen and blood culture. Appropriate treatment would be provided as per hospital protocol. The study would be implemented as per the MRC guideline for the management of Global Health Trials in accordance with ICH-GCP and Indian Regulatory guidelines. A contract research organization would be engaged for comprehensive monitoring and quality assurance. The final analysis would be conducted in a blinded manner as per the statistical analysis plan (SAP) to estimate the primary outcomes of sepsis, possible serious bacterial infection (PSBI), and secondary outcomes. The codes will be broken after DMC permission. The protocol has been reviewed by the Research Ethics Committee of the Liverpool School of Tropical Medicine (REC-LSTM), from Research Ethics Committees of the six subject recruitment participating sites. Discussion This adequately powered and well-designed trial would conclusively answer the question whether probiotics can prevent neonatal sepsis in the high-risk group of low birth weight infants as indicated by a pilot study in 1340 LBW infants, evidence from systematic reviews of hospital-based studies, and a primary study on healthy newborns in Orissa. Results of the study would be generalizable to India and other low–middle-income countries. Trial registration Clinical Trial Registry of India (CTRI) CTRI/2019/05/019197. Registered on 16 May 2019

Double-Blind, Placebo-Controlled Trial of Divalproex Monotherapy in the Treatment of Symptomatic Youth at High Risk for Developing Bipolar Disorder

2007 ◽  
Vol 68 (05) ◽  
pp. 781-788 ◽  
Author(s):  
Robert L. Findling ◽  
Thomas W. Frazier ◽  
Eric A. Youngstrom ◽  
Nora K. McNamara ◽  
Robert J. Stansbrey ◽  
...  
Keyword(s):  
Bipolar Disorder ◽  
High Risk ◽  
Controlled Trial ◽  
Double Blind ◽  
Double Blind Placebo
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