protocol_id stringclasses 263
values | section_number stringlengths 1 12 | title stringlengths 1 1.88k | content stringlengths 0 866k | merged_titles listlengths 0 491 |
|---|---|---|---|---|
NCT03392532 | 10.1 | Informed Consent and Screening | The Investigator or delegate must explain the purpose and nature of the study, and have the subject read, sign, and date the IRB/IEC-approved informed consent document. The subject must sign the ICF BEFORE any study-specific procedures or assessments can be performed, including study-specific screening procedures. Addi... | [] |
NCT03392532 | 10.2 | Description of Study Procedures and Assessments | Detailed descriptions of assessments and procedures are provided in the MOP. The Investigator is responsible for ensuring responsibilities for all procedures and assessments are delegated to appropriately qualified site personnel. | [] |
NCT03392532 | 10.2.1 | Demographics | Obtain demographic information including age, race, ethnicity, and sex. | [] |
NCT03392532 | 10.2.2 | Medical History | Collect medical history information, including information on all medications used within the past 30 days. Include herbal therapies, vitamins, and all over-the-counter as well as
D oc u me nt: Versi o n: 1 . 0 ; C U R R E N T ; M o s t - R e c e n t ; E f f e c t i v e T D O C - 0 0 5 4 4 9 9
Pa ge 3 5 of 5 4 St at ... | [
"1 0. 2. 3 I n vesti g ati o n al Pro d uct c o m pli a nce",
"1 0. 2. 4 A d verse E ve nt C ollecti o n: S afet y Assess me nt",
"1 0. 2. 5 Slit L a m p Bi o micr osc o p y: S afet y Assess me nt",
"1 0. 2. 6 De vice Deficie ncies: S afet y Assess me nt",
"1 0. 2. 7 A d diti o n al St u d y Assess me nts E... |
NCT03392532 | 11 | ADVERSE EVENTS AND DEVICE DEFICIENCIES | [] | |
NCT03392532 | 11.1 | General Information | An AE is any untoward medical occurrence, unintended disease or injury, or untoward clinical signs (including abnormal laboratory findings) in subjects, users, or other persons, whether or not related to the investigational medical device (test article). Refer to the Glossary of Terms and figures below for categories o... | [
"S pecific E ve nts Rele v a nt t o t his Pr ot oc ol",
"Seri o us A dverse Eve nts",
"Si g nific a nt N o n Seri o us A dverse Eve nts",
"Device Deficie ncies",
"1 1. 2 M o nit ori n g f or A d verse E ve nts",
"1 1. 3 Pr oce d ures f or Rec or di n g a n d Re p orti n g",
"I nte nsit y a n d C a us al... |
NCT03392532 | 11.4 | Return product analysis | Study Sponsor representatives and their contact information are provided in the MOP that accompanies this protocol.
Alcon products associated with device deficiencies and/or product related AEs must be returned and must include the Complaint # which will be provided by Study Sponsor after the case is entered in the St... | [] |
NCT03392532 | 11.5 | Unmasking of the Study Treatment | Masked information on the identity of the assigned medical device should not be disclosed during the study (See Section 9.4). If the treatment code needs to be broken in the interest of subject safety, the Investigator is encouraged to contact an appropriate Study Sponsor representative prior to unmasking the informati... | [] |
NCT03392532 | 11.6 | Follow-Up of Subjects with Adverse Events | The Investigator is responsible for adequate and safe medical care of subjects during the study and for ensuring that appropriate medical care and relevant follow-up procedures are maintained after the study.
The Investigator should provide the Study Sponsor with any new safety information (which includes new AEs and ... | [] |
NCT03392532 | 11.7 | Pregnancy in the Clinical Study | Women of childbearing potential or women who are pregnant at the time of study entry are not excluded from participation. Pregnancy should be included in the Medical History section of the eCRF when a pregnant woman enters the study. Pregnancy is not reportable as an AE; however, complications may be reportable and wil... | [] |
NCT03392532 | 12 | ANALYSIS PLAN | Continuous variables will be summarized using the number of observations, mean, standard deviation (SD), median, minimum and maximum, as well as confidence intervals (CI) or confidence limits where applicable. Categorical variables will be summarized with counts and percentages from each category. Any deviations to the... | [] |
NCT03392532 | 12.1 | Subject Evaluability | Final subject evaluability must be determined prior to breaking the code for masked lens sequence assignment and locking the database, based upon the Deviations and Evaluability Plan. | [] |
NCT03392532 | 12.2 | Analysis Sets | [] | |
NCT03392532 | 12.2.1 | Safety Analysis Set | Safety analyses will be conducted using the safety analysis set on a treatment-emergent basis.
Document: Version:
Page 45 of 54 Status: Effective TDOC-0054499 1.0; CURRENT; Most-Recent; Effective Protocol - Clinical 17-Nov-2017
As such, the safety analysis set will include all subjects/eyes exposed to any study le... | [] |
NCT03392532 | 12.2.2 | Full Analysis Set | The full analysis set (FAS) is the set of all randomized subjects who are exposed to any study lenses evaluated in this study. | [] |
NCT03392532 | 12.2.3 | Per Protocol Analysis Set | The per protocol (PP) analysis set is a subset of FAS and excludes all data/subjects which have met any of the critical deviation or evaluability criteria identified in the DEP. | [] |
NCT03392532 | 12.3 | Demographic and Baseline Characteristics | Demographic and baseline characteristics will be summarized by lens sequence and overall. Counts and percentages will be presented for categorical variables such as sex, age group, race, and ethnicity. N, mean, SD, median, minimum, and maximum will be presented for continuous variables such as age. | [] |
NCT03392532 | 12.4 | Effectiveness Analyses | | This study defines 1 primary, | effectiveness |
|-----------------------------------------------------------------------------------------|---------------------------------|
| endpoints. All effectiveness evaluations will use the FAS as the p... | [] |
NCT03392532 | 12.4.1 | Analysis of Primary Effectiveness Endpoint(s) | The primary endpoint is the percent of AOHG toric with axis orientation within ±30 degrees from the 90° axis (ideal location), 10 min after lens insertion. This percentage is calculated for the binary variable derived based on axis location of each lens, as defined below:
Yes – if the absolute difference between the a... | [] |
NCT03392532 | 12.4.1.1 | Statistical Hypotheses | No inferences are to be made on the primary effectiveness endpoint; therefore no hypotheses are formulated. | [] |
NCT03392532 | 12.4.1.2 | Analysis Methods | Frequency and percentage of lenses classified as 'Yes' will be provided for AOHG toric and AO toric, and a two-sided CI will be calculated.
A threshold of 90% (as a minimum) has been established for this endpoint based upon historical data. Therefore, percent of 'Yes' for AOHG toric lenses will be compared numerically... | [
"1 2. 5 H a n dli n g of Missi n g D at a",
"1 2. 6 S afet y A n al ys es"
] |
NCT03392532 | 12.7 | Interim Analyses and Reporting | There are no plans to conduct an interim analysis and no criteria by which the study would be terminated early based upon statistical determination | [] |
NCT03392532 | 12.8 | Sample Size Justification | Although inferential testing is not planned for the primary effectiveness endpoint, expected precision of the observed results is provided. A two-sided 95% confidence interval for a single proportion will extend approximately 0.10 from the observed value when the expected proportion is 0.90, with a sample size of 30.
... | [] |
NCT03392532 | 13 | DATA HANDLING AND ADMINISTRATIVE REQUIREMENTS | [] | |
NCT03392532 | 13.1 | Subject Confidentiality | The Investigator must ensure that the subject's anonymity is maintained throughout the course of the study. In particular, the Investigator must keep an enrollment log with confidential identifying information that corresponds to the subject numbers and initials of each study participant. At the end of the clinical stu... | [] |
NCT03392532 | 13.2 | Completion of Source Documents and Case Report Forms | The nature and location of all source documents will be identified to ensure that original data required to complete the CRFs exist and are accessible for verification by the site monitor, and all discrepancies shall be appropriately documented via the query resolution process. Site monitors are appointed by the Study ... | [
"1 3. 3 D at a Re vie w a n d Cl arific ati o ns"
] |
NCT03392532 | 13.4 | Sponsor and Monitoring Responsibilities | The Study Sponsor will designate a monitor to conduct the appropriate site visits at the appropriate intervals according to the study monitoring plan. The clinical investigation will be monitored to ensure that the rights and well-being of the subjects are protected, the reported data are accurate, complete, and verifi... | [
"1 3. 5 Re g ul at or y D oc u me nt ati o n a n d Rec or ds Rete nti o n",
"1 3. 6 Q u alit y Ass ur a nce a n d Q u alit y C o ntr ol",
"1 4 E T HI C S",
"1 5 R E F E R E N C E S",
"1 5. 1 Refere nces a p p lic a ble f or all cli nic al st u dies",
"1 5. 1. 1 U S refere nces a p plic a ble f or cli nic ... |
NCT03483103 | 1 | INTRODUCTION | [] | |
NCT03483103 | 1.1 | B-cell Non-Hodgkin Lymphoma | It is estimated that approximately 72,000 new cases of non-Hodgkin lymphoma (NHL) will be diagnosed and approximately 20,000 patients will die of their disease in the United States in 2019 [\(Siegel 2019\)](#page-88-0). NHL is the seventh most common cancer in the US, accounting for 4.2% of new cancers and 3.3% of all ... | [] |
NCT03483103 | 1.2 | CD19 as a Therapeutic Target | CD19 is a 95-kDa glycoprotein present on B-cells from early development until differentiation into plasma cells [\(Stamenkovic 1988\)](#page-88-0). It is a member of the immunoglobulin superfamily and a component of a B cell surface signal transduction complex that positively regulates signal transduction through the B... | [] |
NCT03483103 | 1.3 | CD19-Targeted Chimeric Antigen Receptors | CD19-specific chimeric antigen receptors (CARs) are single chain variable fragments (scFv) fused to a transmembrane domain and cytoplasmic signaling domains. Expression of the CD19-directed CAR in autologous T cells is achieved by ex vivo transfection using a recombinant retroviral or lentiviral vector. The CAR is expr... | [] |
NCT03483103 | 1.4 | JCAR017 Investigational Drug Product | The final JCAR017 investigational drug product includes 2 individually formulated CD8+ CAR + and CD4+ T CAR+ cell suspensions in media containing dimethyl sulfoxide (DMSO) that are thawed and infused separately. JCAR017 is administered by intravenous (IV) infusion.
The CD19-specific CAR and truncated human epidermal g... | [] |
NCT03483103 | 1.5 | Clinical Experience with JCAR017 | Study 017001 is an open-label, multicenter, Phase 1 study to determine the antitumor activity, pharmacokinetics (PK), and safety of JCAR017 in adult subjects with R/R DLBCL NOS (de novo and transformed from indolent lymphoma), high-grade B-cell lymphoma with MYC and BCL2 and/or BCL6 rearrangements with DLBCL histology,... | [] |
NCT03483103 | 2 | STUDY PURPOSE AND RATIONALE | Data from Juno Study 017001 demonstrate that treatment with JCAR017 in subjects with aggressive B-cell NHL who have failed 2 or more lines of therapy results in encouraging efficacy results and an acceptable safety profile. Outcomes of patients who have failed front-line therapy are poor, and additional options are nee... | [] |
NCT03483103 | 2.1 | Rationale for JCAR017 Dose Level | As noted in Section [1.5,](#page-28-0) JCAR017 at flat doses of 50×106 CAR+ T cells and 100×106 CAR+ T cells has resulted in durable responses and has demonstrated an acceptable safety profile in the third- or greater line treatment of R/R aggressive DLBCL. Additionally, as of 07 Jul 2017, a trend toward improved ORR a... | [] |
NCT03483103 | 2.2 | Rationale for Study Design | The purpose of this Phase 2 study is to evaluate the efficacy and safety of JCAR017 in adult subjects with aggressive B-NHL who have failed front-line therapy and are not eligible for HSCT. There is no approved standard of care for this population. A non-randomized design was chosen because of the lack of effective the... | [] |
NCT03483103 | 2.3 | Rationale for Lymphodepleting Chemotherapy | As noted in Section [1.5,](#page-28-0) preliminary data available from subjects with R/R NHL in Study 017001 suggest that the low-intensity lymphodepleting chemotherapy regimen used, cyclophosphamide (300 mg/m2 /day × 3 days) combined with fludarabine (30 mg/m2 /day × 3 days), in combination with JCAR017 has adequate s... | [] |
NCT03483103 | 2.4 | Rationale for Endpoints | The efficacy endpoints to be assessed in this study are standard endpoints for the assessment of aggressive B-cell NHL. Disease response will be determined according to the
"Recommendations for Initial Evaluation, Staging, and Response Assessment of Hodgkin and Non-Hodgkin Lymphoma: The Lugano Classification" [\(Cheso... | [] |
NCT03483103 | 2.5 | Risk/Benefit Summary | As discussed in Section [1.1,](#page-23-0) options for treatment of R/R subjects are limited. Transplantineligible subjects have especially limited treatment options as they are not eligible for the most commonly used second-line treatment (HSCT). Administration of JCAR017 has resulted in durable responses in subjects ... | [] |
NCT03483103 | 3 | STUDY OBJECTIVES AND ENDPOINTS | The objectives and corresponding endpoints for the study are presented in [Table](#page-31-1) 2. Efficacy analyses will be based on response assessments per the Independent Review Committee (IRC).
Table 2: Study Objectives and Endpoints
| Objective ... | [] |
NCT03483103 | 4 | STUDY DESIGN AND INVESTIGATIONAL PLAN | [] | |
NCT03483103 | 4.1 | Overall Study Design | This is an open-label, multicenter, Phase 2 study to determine the antitumor activity, PK, and safety of JCAR017 in subjects who have relapsed from, or are refractory to, front-line immunochemotherapy for aggressive B-cell NHL and are ineligible for transplant. Subjects will be treated with lymphodepleting chemotherapy... | [] |
NCT03483103 | 4.2 | Study Duration and Duration of Subject Participation | The duration of study for each subject is approximately 2 years, and the estimated total time from first subject first visit for all subjects to complete the study is approximately 4 years. | [] |
NCT03483103 | 4.3 | Study Completion | A subject is considered to have completed the study if he/she has completed the last scheduled visit shown in the Schedule of Evaluations.
The end of the study is defined as the date of the last scheduled assessment shown in the Schedule of Evaluations for the last subject in the trial. | [] |
NCT03483103 | 4.4 | Study Oversight | [] | |
NCT03483103 | 4.4.1 | Data Safety Monitoring Board | An independent DSMB will review cumulative study data approximately semiannually over the course of the study to evaluate safety, protocol conduct, and scientific validity and integrity of the trial. Subject safety will be evaluated, and the DSMB will provide advice to the Sponsor and study Investigators, as specified ... | [] |
NCT03483103 | 4.4.2 | Independent Review Committee | An IRC will be established to determine response and progression status, as described in more detail in Section [8.3.1.](#page-61-0) | [] |
NCT03483103 | 4.5 | Suspension or Early Termination of the Study | The study can be suspended or terminated at any time by the Sponsor, the Food and Drug Administration (FDA), at the recommendation of the DSMB, or at the recommendation of an IRB. Circumstances that may warrant suspension or termination include, but are not limited to:
- Determination of unexpected, significant, or un... | [] |
NCT03483103 | 5 | STUDY POPULATION | [] | |
NCT03483103 | 5.1 | Inclusion Criteria | Subjects must meet all the following criteria to be enrolled into this study:
- 1. Age ≥ 18 years at the time of consent
- 2. Signed written informed consent obtained prior to any study procedures
- 3. Confirmation of R/R aggressive B-cell NHL of the following histologies at relapse:
- a. DLBCL, not otherwise specif... | [
"Partner's vasectomy"
] |
NCT03483103 | 12 | Male subjects must: | - a. Practice true abstinence3 (which must be reviewed on a monthly basis) or agree to use a condom during sexual contact with a pregnant female or a female of childbearing potential for 12 months after lymphodepleting chemotherapy even if he has undergone a successful vasectomy.
- b. There are insufficient exposure da... | [
"5.2. Exclusion Criteria",
"5.3. Removal of Subjects from Treatment or Study",
"5.3.1. Screen Failures",
"5.3.2. Subject Discontinuation Prior to Receiving Study Treatment",
"5.3.3. Subject Discontinuation from Further Study Treatment",
"5.3.4. Subject Withdrawal from Study",
"5.3.5. Replacement of Stud... |
NCT03483103 | 12 | CONTACT INFORMATION | [] | |
NCT03483103 | 12.1 | Study Sponsor | Juno Therapeutics, Inc. A wholly owned subsidiary of Celgene Corporation 400 Dexter Ave North, Suite 1200 Seattle, WA 98109 Phone: 206-582-1600 www.junotherapeutics.com | [] |
NCT03483103 | 12.2 | Global Drug Safety | | | Pharmacovigilance at Celgene Corporation: | | |
|--------|-------------------------------------------|---------|--|
| Email: | | or fax: | | | [] |
NCT03483103 | 13 | REFERENCES | Abramson JS, Palomba ML, Gordon LI, et al. Pivotal safety and efficacy results from TRANSCEND NHL 001, a multicenter Phase 1 study of lisocabtagene maraleucel (liso-cel) in relapsed/refractory (R/R) large B-cell lymphomas. [abstract]. Blood 2019;134(Suppl 1):241.
Abramson JS, Palomba ML, Gordon LI, et al. High durable... | [
"APPENDIX A. SCHEDULES OF EVALUATIONS",
"Schedule of Evaluations Footnotes:",
"APPENDIX B. RECOMMENDATIONS FOR INITIAL EVALUATION, STAGING, AND RESPONSE ASSESSMENT OF HODGKIN AND NON-HODGKIN LYMPHOMA: THE LUGANO CLASSIFICATION",
"APPENDIX C. COCKCROFT-GAULT EQUATION FOR CALCULATING ESTIMATED CREATININE CLEARA... |
NCT03693300 | 1 | PROTOCOL SUMMARY | [] | |
NCT03693300 | 1.1 | Synopsis |
A Phase II, Open-Label, Multi-Centre, International Safety Study of Durvalumab Following Sequential Chemotherapy and Radiation Therapy in Patients with Stage III, Unresectable Non-Small Cell Lung Cancer (PACIFIC 6)
This study is being conducted to provide safety, efficacy, and quality of life (QoL) data to complemen... | [
"Protocol Title:",
"Rationale:",
"Tumour assessments",
"Progression during treatment",
"Follow-up of patients post discontinuation of study drug",
"Overall survival",
"Steering Committee",
"Interim analysis",
"Statistical methods"
] |
NCT03693300 | 1.2 | Schedule of assessments | The procedures for the screening and treatment periods in this study are presented in Table 1, and the procedures for the follow-up period are presented in Table 2 (Schedule of assessments [SoA]).
Whenever vital sign assessments and blood draws are scheduled for the same nominal time, the assessments should occur in t... | [] |
NCT03693300 | 2 | INTRODUCTION | Lung cancer has been the most common cancer in the world for several decades (WHO 2012). In 2012, there were an estimated 1.8 million new cases, representing 12.9% of all new cancers. It was also the most common cause of death from cancer worldwide, with 1.59 million deaths (19.4% of the total). NSCLC represents approx... | [] |
NCT03693300 | 2.1 | Study rationale | Prior to the PACIFIC Study, minimal advances had been made for the treatment of patients with unresectable Stage III NSCLC. The treatment of choice in patients with unresectable stage IIIA and IIIB NSCLC has been cCRT (Postmus et al 2017, NCCN 2018). If cCRT is not feasible, including in frail patients who are unable t... | [] |
NCT03693300 | 2.2 | Background | [] | |
NCT03693300 | 2.2.1 | Unmet need and potential role of immunotherapies in NSCLC | The addition of systemic therapy to radiation therapy has been reported to improve survival of patients with NSCLC in studies that have used cisplatin-based systemic therapy regimens (Aupérin et al 2006, Non-small Cell Lung Cancer Collaborative Group 1995). cCRT has been found to be more beneficial than sCRT (Fournel e... | [] |
NCT03693300 | 2.2.2 | Immunotherapies | It is increasingly understood that cancers are recognised by the immune system, and under some circumstances, the immune system may control or even eliminate tumours (Dunn et al 2004).
PD-L1 is part of a complex system of receptors and ligands that are involved in controlling T cell activation. The PD-1 receptor (clus... | [] |
NCT03693300 | 2.2.3 | Durvalumab (MEDI4736) | Durvalumab (MEDI4736) is a human mAb of the immunoglobulin G (IgG) 1 kappa subclass that blocks the interaction of PD-L1 (but not programmed cell death ligand-2) with PD-1 on T cells and CD80 (B7.1) on immune cells. It is being developed by AstraZeneca/MedImmune for use in the treatment of cancer (MedImmune is a wholly... | [] |
NCT03693300 | 2.3 | Benefit/risk assessment | The majority of the safety and efficacy data currently available for durvalumab (MEDI4736) are based on the first-in-human, single-agent study (Study 1108) in patients with advanced solid tumours, the study of durvalumab (MEDI4736) monotherapy in NSCLC (Study D4191C00003 [ATLANTIC]), and the study of durvalumab (MEDI47... | [] |
NCT03693300 | 2.3.1 | Potential benefits | The efficacy of durvalumab (MEDI4736) was evaluated in the PACIFIC Study, a multi-centre, randomised, double-blind, placebo-controlled study in patients with unresectable Stage III NSCLC who completed at least 2 cycles of concurrent platinum-based chemotherapy and definitive radiation within 42 days prior to initiation... | [] |
NCT03693300 | 2.3.2 | Overall risks | Monoclonal antibodies directed against immune checkpoint proteins, such as PD-L1, aim to boost endogenous immune responses directed against tumour cells. By stimulating the immune system, however, there is the potential for adverse effects on normal tissues.
Most adverse drug reactions seen with the immune checkpoint ... | [] |
NCT03693300 | 2.3.2.1 | Durvalumab (MEDI4736) risks | Risks with durvalumab (MEDI4736) include, but are not limited to, diarrhoea/colitis, pneumonitis/ILD, endocrinopathies (i.e., events of hypophysitis/hypopituitarism, adrenal insufficiency, hyper- and hypo-thyroidism, type I diabetes mellitus [DM] and diabetes insipidus), hepatitis/increases in transaminases, nephritis/... | [] |
NCT03693300 | 2.3.3 | Overall benefit/risk | In summary, the potential for clinical benefit associated with inhibition of the PD-1/PD-L1 pathway, supported by the clinical benefit in terms of PFS and ORR observed in earlier studies in patients with NSCLC, including the pivotal Phase III PACIFIC Study, outweighs the known and potential risks based on the AEs repor... | [] |
NCT03693300 | 3 | OBJECTIVES AND ENDPOINTS | The study objectives and corresponding endpoints/variables are listed in Table 3.
Table 3 Study objectives
| OBJECTIVE | ENDPOINT/VARIA... | [
"Investigational product, dosage and mode of administration",
"Tumour response assessments",
"Overall survival assessments",
"Schedule of assessments",
"Interim analysis",
"End of analysis portion of study"
] |
NCT03693300 | 4.1.1 | Study Conduct Mitigation During Study Disruptions Due to Cases of Civil Crisis, Natural Disaster, or Public Health Crisis | The guidance given below supersedes instructions provided elsewhere in this CSP and should be implemented only during cases of civil crisis, natural disaster or public health crisis (eg, during quarantines and resulting site closures, regional travel restrictions and considerations if site personnel or study patients b... | [] |
NCT03693300 | 4.2 | Scientific rationale for study design | [] | |
NCT03693300 | 4.2.1 | Rationale for study safety endpoints | This study is designed to further evaluate the safety of durvalumab (MEDI4736) monotherapy, using a fixed-dosing regimen, in unresectable Stage III NSCLC patients who have not progressed following definitive, platinum-based sCRT. This study is designed to complement and expand the safety database from the ongoing Phase... | [] |
NCT03693300 | 4.2.2 | Rationale for study efficacy endpoints | The secondary aim of this study is to determine the efficacy of durvalumab (MEDI4736) 1500 mg q4w in terms of PFS and OS. PFS has been found to be correlated with OS in previous CRT studies (Mauguen et al 2013). Although the OS benefit has exceeded the PFS benefit in other studies of immune checkpoint inhibitors in adv... | [] |
NCT03693300 | 4.2.3 | Rationale for other study exploratory endpoints | 
 | [] |
NCT03693300 | 4.2.4 | Rationale for treatment duration | Treatment in this study will continue up to 24 months or until RECIST 1.1-defined PD and Investigator determination that the patient is no longer benefitting from treatment with IP, or until another discontinuation criterion is met (see Section 7.1). This guidance is supported by data from the CheckMate-153 Study that ... | [] |
NCT03693300 | 4.2.5 | Timing of treatment with durvalumab (MEDI4736) relative to sequential chemoradiation therapy | Non-clinical data show that both chemotherapy and ionising radiation up-regulate PD-L1 expression (Deng et al 2014, Zhang et al 2008). In addition, chemotherapy and radiotherapy both release new antigens leaving the cancer to act as an in situ vaccine that can elicit tumour-specific T cells. Thus, starting durvalumab (... | [] |
NCT03693300 | 4.3 | Justification for dose | This study will utilise a fixed dose for durvalumab (MEDI4736) treatment (1500 mg q4w IV). Based on an average body weight of 75 kg, a fixed dose of 1500 mg of durvalumab (MEDI4736) q4w is equivalent to a weight-based dose of 20 mg/kg q4w. | [] |
NCT03693300 | 4.3.1 | Durvalumab (MEDI4736) monotherapy dose rationale | A durvalumab (MEDI4736) dose of 20 mg/kg q4w is supported by in-vitro data, non-clinical activity, clinical PK/pharmacodynamics (PDx), biomarkers, and activity data from Study 1108 in patients with advanced solid tumours and from a Phase I study performed in Japanese patients with advanced solid tumour (D4190C00002).
... | [
"Pharmacokinetics/pharmacodynamics data",
"Clinical data"
] |
NCT03693300 | 4.3.2 | Rationale for fixed dosing | A population PK model was developed for durvalumab (MEDI4736) using monotherapy data from Study 1108 and the PACIFIC Study (n=1310, doses including 10 mg/kg q2w or 15 mg/kg q3w or 20 mg/kg q4w; solid tumours). Population PK analysis indicated only minor impact of body weight on the PK of durvalumab (MEDI4736) (coeffici... | [] |
NCT03693300 | 4.3.3 | Predictive biomarkers and rationale for an unselected population in the PACIFIC 6 Study | For this study, enrolment is not restricted to any biomarker-defined sub-population, but where possible, these patient characteristics are assessed in an exploratory manner and in the context of this study and other studies.
In the PACIFIC Study, benefit was also observed irrespective of PD-L1 status. Indeed, no signi... | [] |
NCT03693300 | 4.4 | End of study definition | The end of the study is defined as the last visit of the last patient undergoing the study. A patient is considered to have completed the study when he/she has completed his/her last study visit per protocol.
The final DCO is planned to occur when the last patient had the opportunity to receive durvalumab (MEDI4736) f... | [] |
NCT03693300 | 5 | STUDY POPULATION | Prospective approval of protocol deviations to recruitment and enrolment criteria, also known as protocol waivers or exemptions, is not permitted.
Each patient should meet all of the inclusion criteria and none of the exclusion criteria for this study in order to receive IP treatment. Under no circumstances can there ... | [] |
NCT03693300 | 5.1 | Inclusion criteria | For inclusion in the study, patients should fulfil the following criteria:
- 1 Capable of giving signed informed consent, which includes compliance with the requirements and restrictions listed in the ICF and in this protocol.
- 2 Provision of signed and dated, written ICF prior to any mandatory study specific procedu... | [
"Informed consent",
"Age",
"Type of patient and disease characteristics",
"Weight",
"Sex",
"Reproduction"
] |
NCT03693300 | 5.2 | Exclusion criteria | Patients should not enter the study if any of the following exclusion criteria are fulfilled:
- 1 Patients with locally-advanced NSCLC whose disease has progressed following platinum-based sCRT.
- 2 Patients who have disease considered for surgical treatment as part of their care plan, such as Pancoast or superior sul... | [
"Medical conditions",
"Prior/concomitant therapy",
"Prior/concurrent clinical study experience",
"Other exclusions"
] |
NCT03693300 | 5.3 | Lifestyle restrictions | The following restrictions apply while the patient is receiving IP and for the specified times before and after:
- 1 Female patients of childbearing potential
- (a) Female patients of childbearing potential who are not abstinent and intend to be sexually active with a non-sterilized male partner must use at least 1 ... | [] |
NCT03693300 | 5.4 | Patient enrolment | All patients will be centrally assigned to study drug using an Interactive Voice Response System (IVRS)/Interactive Web Response System (IWRS). Before the study is initiated, the telephone number and call-in directions for the IVRS and/or the log-in information and directions for the IWRS will be provided to each site.... | [] |
NCT03693300 | 5.5 | Procedures for handling incorrectly enrolled patients | Patients who fail to meet the eligibility criteria should not, under any circumstances, be enrolled or receive the study drug. There can be no exceptions to this rule. Patients who are enrolled, but subsequently found not to meet all the eligibility criteria, must not be initiated on treatment, and must be withdrawn fr... | [] |
NCT03693300 | 5.6 | Screen failures | Screen failures are patients who do not fulfil the eligibility criteria for the study, and therefore must not be dosed. These patients should have the reason for study withdrawal recorded as "screen failure". This reason for study withdrawal is only valid for screen failures (ie, not for patients who are assigned IP tr... | [] |
NCT03693300 | 6 | STUDY TREATMENTS | Study treatment is defined as any IPs (including marketed product comparator and placebo) intended to be administered to a study participant according to the study protocol. Study treatment in this study refers to durvalumab (MEDI4736). | [] |
NCT03693300 | 6.1 | Treatments administered | [] | |
NCT03693300 | 6.1.1 | Investigational product | AstraZeneca will supply durvalumab (MEDI4736) (described in Table 5).
Table 5 Study treatment
| Study treatment name | Durvalumab (MEDI4736) | |
|--------------------------|------------------------------------------------... | [
"Preparation of durvalumab (MEDI4736) doses for administration with an IV bag"
] |
NCT03693300 | 6.1.2 | Dose and treatment regimens | Patients will receive 1500 mg durvalumab (MEDI4736) monotherapy via IV infusion q4w for up to a maximum of 24 months from Cycle 1 Day 1 (up to 26 doses/cycles) with the last administration at Week 104 (Figure 3). The study drug should be discontinued prior to 24 months if there is clinical progression or confirmed radi... | [] |
NCT03693300 | 6.1.3 | Duration of treatment and criteria for treatment through progression and discontinuation | Patients with CR, PR, or SD (based on Investigator assessment) following completion of sCRT will receive durvalumab (MEDI4736) treatment for a maximum of 24 months or until RECIST 1.1‑defined PD (unless the Investigator considers the patient continues to receive benefit from the IP), initiation of alternative cancer th... | [
"Treatment after final overall survival data cut-off"
] |
NCT03693300 | 6.1.4 | Storage | The Investigator, or an approved representative (eg, pharmacist), will ensure that all IP is stored in a secured area, at refrigerated temperatures (2°C to 8°C) and in accordance with applicable regulatory requirements. A temperature log will be used to record the temperature of the storage area. Temperature excursions... | [] |
NCT03693300 | 6.2 | Measures to minimise bias: randomisation and blinding | Not applicable. | [] |
NCT03693300 | 6.3 | Treatment compliance | All administrations of the IP should be recorded in the appropriate sections of the electronic case report form (eCRF).
Any change from the dosing schedule, dose interruptions, dose reductions, and dose discontinuations should be recorded in the eCRF.
Treatment compliance will be ensured by reconciliation of site dru... | [] |
NCT03693300 | 6.4 | Concomitant therapy | The Investigator must be informed as soon as possible about any medication taken from the time of screening until the end of the clinical treatment phase of the study (ie, until 90 days after last dose of IP), including the follow-up period following the last dose of IP.
Any medication or vaccine including over-the-co... | [] |
NCT03693300 | 6.4.1 | Other concomitant treatment | Medication, other than the supportive medication listed in Table 7, that is considered necessary for the patient's safety and well-being, may be given at the discretion of the Investigator and recorded in the appropriate sections of the eCRF. | [] |
NCT03693300 | 6.4.2 | Durvalumab (MEDI4736) drug-drug interactions | There is no information to date on drug-drug interactions with durvalumab (MEDI4736) either pre-clinically or in patients. As durvalumab (MEDI4736) is an mAb and therefore a protein, it will be degraded to small peptides and amino acids and will be eliminated by renal and reticuloendothelial clearance. It is therefore ... | [] |
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