protocol_id stringclasses 263
values | section_number stringlengths 1 12 | title stringlengths 1 1.88k | content stringlengths 0 866k | merged_titles listlengths 0 491 |
|---|---|---|---|---|
NCT03907969 | 4.4 | End of study definition | 4.4 End of study definition The end of study is defined as the last visit of the last patient undergoing the protocol-defined assessments. The study may be terminated at individual centres if the study procedures are not being performed according to GCP, or recruitment is low. AstraZeneca may also terminate the entire ... | [] |
NCT03907969 | 5 | STUDY POPULATION | 5 STUDY POPULATION Prospective approval of protocol deviations to recruitment and enrolment criteria, also known as protocol waivers or exemptions, are not permitted. Each patient should meet all of the inclusion criteria and none of the exclusion criteria for the core and Combination Module 1 (if applicable). Under no... | [] |
NCT03907969 | 5.1 | Inclusion criteria | 5.1 Inclusion criteria The inclusion criteria that are applicable to all parts/cohorts of the study are described in this section. Please refer to Section 13.1 for additional specific criteria applicable to Combination Module 1.
Informed Consent - 1 Capable and willing to give signed informed consent which includes co... | [
"Informed Consent",
"Age",
"Type of Patient and Disease Characteristics",
"Reproduction"
] |
NCT03907969 | 5.2 | Exclusion criteria | 5.2 Exclusion criteria The exclusion criteria that are applicable to all parts/cohorts of the study are described in this section. Please also refer to Section 13.2 for additional specific criteria applicable to Combination Module 1.
Medical Conditions - 1 Any unresolved toxicities from prior therapy CTCAE Grade ≥ 2 (... | [
"Medical Conditions",
"Prior/Concomitant Therapy",
"Prior/Concurrent Clinical Study Experience",
"Diagnostic Assessments",
"Other Exclusions"
] |
NCT03907969 | 5.3 | Lifestyle restrictions | 5.3 Lifestyle restrictions | [] |
NCT03907969 | 5.3.1 | Fasting restrictions | 5.3.1 Fasting restrictions AZD7648 tablets should be swallowed whole with water on an empty stomach (no food or drink other than water for 2 hours prior to dosing and 1 hour after dosing). | [] |
NCT03907969 | 5.3.2 | Dietary restrictions | 5.3.2 Dietary restrictions During the studies, patients should avoid consuming grapefruits, Seville oranges, or other products that may contain these fruits as these may affect AZD7648 metabolism. | [] |
NCT03907969 | 5.3.3 | Contraception | 5.3.3 Contraception
Male patients - Should use barrier contraceptives (ie, by use of condoms) during sex with all partners from the time they sign consent and for 12 weeks after the last dose of study treatment. If male patients wish to father children, they should be advised to arrange for freezing of sperm samples p... | [
"Male patients",
"Female patients"
] |
NCT03907969 | 5.3.4 | Concomitant medication | 5.3.4 Concomitant medication See Section 6.5, for details in restricted or prohibited medications. | [] |
NCT03907969 | 5.3.5 | Blood donation | 5.3.5 Blood donation Patients should not donate blood whilst participating in studies of AZD7648 and for at least 12 weeks after receiving the last dose of study treatment. | [] |
NCT03907969 | 5.4 | Screen failures | 5.4 Screen failures Screen failures are defined as patients who signed the ICF to participate in the clinical study but are not subsequently dosed with study treatment. A minimal set of screen failure information is required to ensure transparent reporting of screen failure patients to meet the Consolidated Standards o... | [] |
NCT03907969 | 6 | STUDY TREATMENTS | 6 STUDY TREATMENTS Study treatment is defined as any investigational product(s) (including marketed product comparator and placebo) or medical device(s) intended to be administered to a study participant according to the study protocol. Study treatment in the Core Module refers to AZD7648 (Table 3). Further details on ... | [] |
NCT03907969 | 6.1 | Treatments administered | 6.1 Treatments administered | [] |
NCT03907969 | 6.1.1 | Investigational products | 6.1.1 Investigational products Table 3 Study treatments | Study treatment name: | AZD7648 | |-----------------------------|-----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------... | [] |
NCT03907969 | 6.1.2 | Dose escalation scheme – Core Module | 6.1.2 Dose escalation scheme – Core Module The dose escalation study flow chart for the Core Module is presented in Figure 6; further details on the dose escalation for Combination Module 1 can be found in Section 14.1.2 AZD7648 will be administered as an oral dose, initially (refer to Figure 7). The individual patient... | [
"Triggers for Additional Modules"
] |
NCT03907969 | 6.1.2.1 | Optional Expansion Cohorts | 6.1.2.1 Optional Expansion Cohorts In all modules of the study, Part A cohorts may be expanded at doses at or above the MBAD in parallel to continuing the dose escalation cohorts provided that the dose has been declared as tolerated. Using this design, tolerability and PK will be characterised in the Part A population ... | [
"Food Effect"
] |
NCT03907969 | 6.1.3 | Definition of dose-limiting toxicity | 6.1.3 Definition of dose-limiting toxicity DLTs will be evaluated during Cycle 0 and Cycle 1 of treatment. Toxicity will be graded according to the National Cancer Institute CTCAE v5.0. A DLT is defined as an AE that occurs from the first dose of study treatment up to and including Cycle 1, Day 28 (the DLT assessment p... | [
"Haematological Toxicities:",
"Non-haematological Toxicity CTCAE Grade ≥3 Including:",
"DLT Will not Include the Following:"
] |
NCT03907969 | 6.1.3.1 | Definition of Maximum Tolerated Dose and Recommended Phase II Dose | 6.1.3.1 Definition of Maximum Tolerated Dose and Recommended Phase II Dose The MTD is defined as the highest dose at which the predicted probability of a DLT is less than 25% (for monotherapy) or 30% (for combinations). At least 6 evaluable patients are required to determine the MTD (refer to Section 6.1.2 for a detail... | [] |
NCT03907969 | 6.1.3.2 | Definition of Maximum Feasible Dose | 6.1.3.2 Definition of Maximum Feasible Dose A dose and schedule will be considered to be the MFD and dose escalation will stop if: - There is evidence of saturation of absorption from emerging PK data that limits the exposure and/or - An MFD has been reached, based on a maximum number of tablets per dose or day, or the... | [] |
NCT03907969 | 6.1.4 | Safety review committee | 6.1.4 Safety review committee The SRC Remit document for this study will define the exact membership and who will be present for decisions to be made. The SRC will guide all dose escalation and cohort expansion decisions in this study. The dose or schedule for subsequent cohorts or a decision to stop recruitment will b... | [] |
NCT03907969 | 6.2 | Preparation/handling/storage/accountability | 6.2 Preparation/handling/storage/accountability The Investigator or designee must confirm appropriate temperature conditions have been maintained during transit for all study treatment received and any discrepancies are reported and resolved before use of the study treatment. Only patients enrolled in the study may rec... | [] |
NCT03907969 | 6.3 | Measures to minimise bias: randomisation and blinding | 6.3 Measures to minimise bias: randomisation and blinding This is an open-label study; no blinding is required. In case of parallel recruitment to Part A and Part B (in the combination modules), a suitable patient allocation system will be implemented to manage any potential bias. If an unscheduled assessment is perfor... | [] |
NCT03907969 | 6.4 | Treatment compliance | 6.4 Treatment compliance The first single dose of AZD7648 will be taken whilst the patient is in the clinic (Cycle 0, Day 1) and the administration of this dose will be recorded in the appropriate section of the CRF. From Cycle 1 onwards, patients will self-administer AZD7648. All patients will be required to complete ... | [] |
NCT03907969 | 6.5 | Concomitant therapy | 6.5 Concomitant therapy Unless clinically indicated, patients should avoid taking additional non-study medications that may interfere with the study treatments. Any medication or vaccine, including over-the-counter or prescription medicines, that the patient is receiving at the time of enrolment or receives during the ... | [] |
NCT03907969 | 6.5.1 | Other concomitant treatment | 6.5.1 Other concomitant treatment Other medication other than that described above, which is considered necessary for the patient's safety and wellbeing, may be given at the discretion of the Investigator and recorded in the appropriate sections of the CRF. If the Investigator, based on his medical judgement, feels tha... | [] |
NCT03907969 | 6.5.2 | Support medication | 6.5.2 Support medication There is no antidote medication for AZD7648; restricted medications are described in Appendix F. Rescue medication for PLD in Combination Module 1 will follow the local label. The use of rescue medications is allowable at any time during the study. The date and time of rescue medication adminis... | [] |
NCT03907969 | 6.6 | Dose modification | 6.6 Dose modification Details of dose escalation can be found in Section 6.1.2. Study treatment will be repeated in 28-day cycles. The dosing criteria for Day 1 of a new cycle of study treatment (blood tests should be reviewed prior to dosing) and continuation of treatment are: - ANC ≥ 1500 cells/mm3 (≥ 1.5 x 109 /L) -... | [] |
NCT03907969 | 6.7 | Treatment after the end of the study | 6.7 Treatment after the end of the study Patients are permitted to either receive standard of care therapy, or to continue to receive study treatment following the end of the study if, in the opinion of the Investigator, they are continuing to receive benefit from treatment. After discontinuation of study treatment, th... | [] |
NCT03907969 | 7 | PATIENT DISCONTINUATION OF TREATMENT AND PATIENT WITHDRAWAL | 7 PATIENT DISCONTINUATION OF TREATMENT AND PATIENT WITHDRAWAL | [] |
NCT03907969 | 7.1 | Discontinuation of study treatment | 7.1 Discontinuation of study treatment Patients may be discontinued from study treatment in the following situations. Note that discontinuation from study treatment is NOT the same as a complete withdrawal from the study: - Disease progression (confirmed progression or symptomatic deterioration or confirmed progression... | [] |
NCT03907969 | 7.1.1 | Temporary discontinuation | 7.1.1 Temporary discontinuation See Section 6.6 for further details on study treatment interruptions. | [] |
NCT03907969 | 7.1.2 | Rechallenge | 7.1.2 Rechallenge See Section 6.6 for further details on study treatment interruptions. | [] |
NCT03907969 | 7.1.3 | Procedures for discontinuation of study treatment | 7.1.3 Procedures for discontinuation of study treatment The Investigator should instruct the patient to contact the site before or at the time if study treatment is stopped. A patient that decides to discontinue study treatment will always be asked about the reason(s) and the presence of any AEs. The date of last intak... | [] |
NCT03907969 | 7.2 | Lost to follow-up | 7.2 Lost to follow-up A patient will be considered potentially lost to follow-up if he or she fails to return for scheduled visits and is unable to be contacted by the study site. The following actions must be taken if a patient fails to return to the clinic for a required study visit: - The site must attempt to contac... | [] |
NCT03907969 | 7.3 | Withdrawal from the study | 7.3 Withdrawal from the study A patient may withdraw from the study (eg, withdraw consent), at any time (study treatment and assessments) at his/her own request, without prejudice to further treatment. A patient who considers withdrawing from the study must be informed by the Investigator about modified follow-up optio... | [] |
NCT03907969 | 8 | STUDY ASSESSMENTS AND PROCEDURES | 8 STUDY ASSESSMENTS AND PROCEDURES Study procedures and their timing are summarised in the SoA. The Investigator will ensure that data are recorded on the CRF. The Web Based Data Capture system will be used for data collection and query handling. The Investigator ensures the accuracy, completeness and timeliness of the... | [] |
NCT03907969 | 8.1 | Efficacy assessments | 8.1 Efficacy assessments | [] |
NCT03907969 | 8.1.1 | Tumour assessments by CT or MRI | 8.1.1 Tumour assessments by CT or MRI RECIST 1.1 guidelines for measurable and non-measurable TLs and non-target lesions (NTLs) and the objective tumour response criteria are presented in Appendix H of this protocol. At baseline, the imaging modalities used for assessment should be contrast enhanced computed tomography... | [] |
NCT03907969 | 8.1.2 | Tumour evaluation | 8.1.2 Tumour evaluation Categorisation of objective tumour response assessment will be based on the RECIST 1.1 criteria of response: CR, PR, and SD (see Appendix H). The CR and PR will need to be confirmed. In addition, the objective tumour response assessment will also be assessed for exploratory analysis on a modifie... | [] |
NCT03907969 | 8.1.3 | Survival assessment | 8.1.3 Survival assessment In Part B of Combination Module 1, survival status will be obtained for all patients who receive study treatment. Vital status (dead or alive; date of death) will be collected every 3 months (±1 week) post-permanent discontinuation of study treatment. To aid the interpretation of the survival ... | [] |
NCT03907969 | 8.2 | Safety assessments | 8.2 Safety assessments Planned time points for all safety assessments are provided in the SoA. | [] |
NCT03907969 | 8.2.1 | Clinical safety laboratory assessments | 8.2.1 Clinical safety laboratory assessments See Table 8 for the list of clinical safety laboratory tests to be performed and to the SoA for the timing and frequency. All protocol-required laboratory assessments, as defined in the table, must be conducted in accordance with the Laboratory Manual and the SoA. The Invest... | [] |
NCT03907969 | 8.2.2 | Physical examinations | 8.2.2 Physical examinations Physical examinations will be conducted at visits described in the SoA; height will be measured at screening only. A complete physical examination will include an assessment of the following: general appearance, respiratory, cardiovascular, abdomen, pelvis, skin, head and neck (including ear... | [] |
NCT03907969 | 8.2.3 | Body weight | 8.2.3 Body weight Body weight will be recorded at each visit as indicated in the SoA. | [] |
NCT03907969 | 8.2.4 | Vital signs | 8.2.4 Vital signs - Oral temperature (in degrees Celsius), pulse rate, respiratory rate, and blood pressure will be assessed. - Blood pressure and pulse measurements will be assessed in supine or sitting position with a completely automated device. Manual techniques will be used only if an automated device is not avail... | [] |
NCT03907969 | 8.2.5 | Electrocardiograms | 8.2.5 Electrocardiograms - In Part A: triplicate 12-lead ECG will be obtained for all timepoints using an ECG machine that automatically calculates the heart rate and measures PR, QRS, QT, and QTc intervals. For triplicate ECG measurements, 3 individual ECG tracings should be obtained in succession, no more than 2 minu... | [] |
NCT03907969 | 8.2.6 | Performance status | 8.2.6 Performance status The patient's performance status will be assessed at screening using the ECOG PS scale. Patients must have an ECOG PS of 0 to 1 to be eligible for enrolment. These scales and criteria are used by doctors and researchers to assess how a patient's disease is progressing, assess how the disease af... | [] |
NCT03907969 | 8.3 | Collection of adverse events | 8.3 Collection of adverse events The Principal Investigator is responsible for ensuring that all staff involved in the study are familiar with the content of this section. The definitions of an AE or SAE can be found in Appendix B. AE will be reported by the patient (or, when appropriate, by a caregiver, surrogate, or ... | [] |
NCT03907969 | 8.3.1 | Method of detecting AEs and SAEs | 8.3.1 Method of detecting AEs and SAEs Care will be taken not to introduce bias when detecting AEs and/or SAEs. Open-ended and non-leading verbal questioning of the patient is the preferred method to inquire about AE occurrences. | [] |
NCT03907969 | 8.3.2 | Time period and frequency for collecting AE and SAE information | 8.3.2 Time period and frequency for collecting AE and SAE information AEs will be collected from time of signature of ICF throughout the treatment period and including the 28-day follow-up visit after treatment discontinuation. All SAEs will be recorded from the time of signing of ICF until the 28-day follow-up visit a... | [] |
NCT03907969 | 8.3.3 | Follow-up of AEs and SAEs | 8.3.3 Follow-up of AEs and SAEs After the initial AE/SAE report, the Investigator is required to proactively follow each patient at subsequent visits/contacts. All events will be followed until resolution, stabilization, the event is otherwise explained, or the patient is lost to follow-up. Any AEs that are unresolved ... | [] |
NCT03907969 | 8.3.4 | AE data collection | 8.3.4 AE data collection The following variables will be collected for each AE: - Adverse event (verbatim) - The date and time when the AE started and stopped - The CTCAE grade (v5.0) and changes in CTCAE grade with the date they changed - Whether the AE is serious or not - Investigator causality rating against the Inv... | [] |
NCT03907969 | 8.3.5 | Causality collection | 8.3.5 Causality collection The Investigator will assess causal relationship between study treatment and each AE, and answer 'yes' or 'no' to the question 'Do you consider that there is a reasonable possibility that the event may have been caused by the study treatment?' For SAEs, causal relationship will also be assess... | [] |
NCT03907969 | 8.3.6 | AEs based on signs and symptoms | 8.3.6 AEs based on signs and symptoms All AEs spontaneously reported by the patient or reported in response to the open question from the study site staff 'Have you had any health problems since the previous visit/you were last asked?' or revealed by observation will be collected and recorded in the CRF. When collectin... | [] |
NCT03907969 | 8.3.7 | AEs based on examinations and tests | 8.3.7 AEs based on examinations and tests The results from the CSP mandated laboratory tests and vital signs will be summarised in the CSR. Deterioration as compared to baseline in protocol-mandated laboratory values, vital signs and clinical safety laboratory tests should therefore only be reported as AEs if they fulf... | [] |
NCT03907969 | 8.3.8 | Hy's law | 8.3.8 Hy's law Cases where a patient shows elevations in liver biochemistry may require further evaluation and occurrences of AST or ALT ≥ 3 x ULN together with TBL ≥ 2 x ULN may need to be reported as SAEs. Please refer to Appendix E for further instruction on cases of increases in liver biochemistry and evaluation of... | [] |
NCT03907969 | 8.3.9 | Disease progression | 8.3.9 Disease progression Disease progression can be considered as a worsening of a patient's condition attributable to the disease for which the study treatment is being studied. It may be an increase in the severity of the disease under study and/or increases in the symptoms of the disease. The development of new, or... | [] |
NCT03907969 | 8.3.10 | New cancers | 8.3.10 New cancers The development of a new cancer should be regarded as an SAE. New primary cancers are those that are not the primary reason for the administration of the study treatment and have been identified after the patient's inclusion in this study. They do not include metastases of the original cancer. | [] |
NCT03907969 | 8.3.11 | Deaths | 8.3.11 Deaths All deaths that occur during the study treatment period, or within the protocol-defined follow-up period after the administration of the last dose of study treatment, must be reported as follows: - Death clearly resulting from disease progression should be reported to the study Investigator at the next mo... | [] |
NCT03907969 | 8.4 | Safety reporting and medical management | 8.4 Safety reporting and medical management | [] |
NCT03907969 | 8.4.1 | Reporting of SAEs | 8.4.1 Reporting of SAEs All SAEs have to be reported, whether or not considered causally related to the study treatment, or to the study procedure(s). All SAEs will be recorded in the CRF. If any SAE occurs in the course of the study, then Investigators or other site personnel inform the appropriate AstraZeneca represe... | [] |
NCT03907969 | 8.4.2 | Pregnancy | 8.4.2 Pregnancy All pregnancies and outcomes of pregnancy should be reported to AstraZeneca except for: If the pregnancy is discovered before the study patient has received any study treatment If a pregnancy is reported, the Investigator should inform the Sponsor within 24 hours of learning of the pregnancy. Abnormal p... | [] |
NCT03907969 | 8.4.2.1 | Maternal Exposure | 8.4.2.1 Maternal Exposure If a patient becomes pregnant during the course of the study, study treatment should be discontinued immediately but the patient will remain in the study. Pregnancy itself is not regarded as an AE unless there is a suspicion that the study treatment may have interfered with the effectiveness o... | [] |
NCT03907969 | 8.4.2.2 | Paternal Exposure | 8.4.2.2 Paternal Exposure Information on the pregnancy of a patient's partner must be obtained directly from the patient's partner. Therefore, prior to obtaining information on the pregnancy, the Investigator must obtain the consent of the patient's partner. Male patients must refrain from fathering a child or donating... | [] |
NCT03907969 | 8.4.3 | Overdose | 8.4.3 Overdose For this study, any dose of AZD7648 in excess of those specified in the protocol will be considered an overdose. Further details on the combination treatments can be found in the relevant combination module protocol. There is currently no specific treatment in the event of overdose of AZD7648 and possibl... | [] |
NCT03907969 | 8.4.4 | Medication error | 8.4.4 Medication error If a medication error occurs during the study, then the Investigator or other site personnel informs the appropriate AstraZeneca representatives within 1 day ie, immediately but no later than 24 hours of when he or she becomes aware of it. The designated AstraZeneca representative works with the ... | [] |
NCT03907969 | 8.4.5 | Management of IP-related toxicities | 8.4.5 Management of IP-related toxicities Details of DLTs can be found in Section 6.6. | [] |
NCT03907969 | 8.5 | Pharmacokinetics | 8.5 Pharmacokinetics Venous blood samples (2 mL) for determination of concentrations of AZD7648 and the potential metabolites (if any) in plasma will be taken at times presented in Table 10. Samples will be split to provide plasma for the primary analysis and secondary/backup analyses. The backup sample may be used for... | [
"PK Window",
"Pharmacokinetic Sampling for Food Effect (if conducted)"
] |
NCT03907969 | 8.5.1 | Determination of drug concentration | 8.5.1 Determination of drug concentration Samples for determination of AZD7648 and PLD (as total doxorubicin) concentrations in plasma, and AZD7648 concentrations in urine will be analysed by Covance on behalf of AstraZeneca, using appropriate bioanalytical methods. Full details of the analytical methods used will be d... | [] |
NCT03907969 | 8.5.2 | Determination of 4β-hydroxy cholesterol concentrations for assessment of CYP3A4 induction potential | 8.5.2 Determination of 4β-hydroxy cholesterol concentrations for assessment of CYP3A4 induction potential Blood samples will be collected from all patients at pre-dose of Cycle 0, Day 1; Cycle 1, Day 8, and Cycle 2, Day 1 in the AZD7648 monotherapy for the determination of 4β-hydroxy cholesterol concentrations in plasm... | [] |
NCT03907969 | 8.5.3 | Storage and destruction of pharmacokinetic samples | 8.5.3 Storage and destruction of pharmacokinetic samples PK samples will be disposed of after the Bioanalytical Report finalisation or 6 months after issuance of the draft Bioanalytical Report (whichever is earlier), unless requested for future analyses. Pharmacokinetic samples may be disposed of or anonymised by pooli... | [] |
NCT03907969 | 8.6 | Pharmacodynamics | 8.6 Pharmacodynamics 
Investigation of PK/PD Relationship Where possible, population modelling and simulation methods will be used as part of the evaluation to assess relationships between emerging safety, tolerability, PK and PD and covariates data. AstraZeneca will be responsible for these ana... | [
"Investigation of PK/PD Relationship"
] |
NCT03907969 | 8.6.1 | Collection of blood for pharmacodynamics biomarker analysis | 8.6.1 Collection of blood for pharmacodynamics biomarker analysis | [] |
NCT03907969 | 8.6.1.1 | Collection of peripheral blood for pharmacodynamics biomarker analysis | 8.6.1.1 Collection of peripheral blood for pharmacodynamics biomarker analysis The collection of blood-based is mandatory in all parts of the study to obtain a preliminary assessment of . Peripheral blood CCI CCI samples will be collected pre-dose and 2 to 4 hours post-dose for AZD7648 as detailed in Table 12 and the S... | [] |
NCT03907969 | 8.6.3 | Collection of tumour samples for pharmacodynamics assessments | 8.6.3 Collection of tumour samples for pharmacodynamics assessments Fresh tumour biopsies are optional for all patients, unless they are enrolled into a Part A PD expansion cohort in which case, they are mandatory. - Serial biopsies will be collected during screening, on treatment (any time in Cycle 1 between Day 3 and... | [] |
NCT03907969 | 8.7 | Genetics | 8.7 Genetics | [] |
NCT03907969 | 8.7 | 1 | 8.7.1 Approximately 10 mL blood sample for DNA isolation will be collected from patients who have consented to participate in the genetic analysis component of the study. Participation is optional. Patients who do not wish to participate in the genetic research may still participate in the study. ![](page83Figure13.jpe... | [] |
NCT03907969 | 8.7.2 | Storage and destruction of genetic samples | 8.7.2 Storage and destruction of genetic samples The processes adopted for the coding and storage of samples for genetic analysis are important to maintain patient confidentiality. Samples may be stored for a maximum of 15 years or as per local regulations from the date of the Last Patient's Last Visit, after which the... | [
"Archival Tumour Samples",
"Other Optional Samples for Biomarker Research"
] |
NCT03907969 | 8.8.1 | Storage, re-use and destruction of biomarker samples | 8.8.1 Storage, re-use and destruction of biomarker samples Samples will be stored for a maximum of 15 years from the date of the Last Patient's Last Visit, after which they will be destroyed. The results of this biomarker research will be reported either in the CSR itself or as an addendum, or separately in a scientifi... | [] |
NCT03907969 | 8.9 | Health Economics | 8.9 Health Economics Health Economics parameters are not evaluated in this study. | [] |
NCT03907969 | 9 | STATISTICAL CONSIDERATIONS | 9 STATISTICAL CONSIDERATIONS | [] |
NCT03907969 | 9.1 | Statistical hypotheses | 9.1 Statistical hypotheses No statistical hypotheses are planned in this study. | [] |
NCT03907969 | 9.2 | Sample size determination | 9.2 Sample size determination Approximately 192 evaluable patients may be enrolled in the Core Module (95 evaluable patients: 46 patients in the dose escalation (Part A) and up to 49 additional patients in optional expansion cohorts) and Combination Module 1 (97 evaluable patients: 30 patients in the dose escalation wi... | [
"Core Module: Monotherapy AZD7648"
] |
NCT03907969 | 9.3 | Populations for analyses | 9.3 Populations for analyses For purposes of analysis, the following analysis sets are defined: | Analysis set | Definition | |-------------------------------------|-----------------------------------------------------------------------------------------------------------------------------------------------------------... | [] |
NCT03907969 | 9.4 | Statistical analyses | 9.4 Statistical analyses The statistical analyses will be performed by Parexel or other designated third-party providers, under the direction of the Biostatistics Group, AstraZeneca. Further detail will be provided in the Statistical Analysis Plan (SAP). Data from each part/module will be presented separately. All pati... | [
"Demographic Data",
"Exposure"
] |
NCT03907969 | 9.4.1 | Efficacy analyses | 9.4.1 Efficacy analyses These are secondary variables. The efficacy assessment of Part A (dose escalation) will be done using ORR. All efficacy endpoints will be used in Part B (expansions) efficacy assessment.
Tumour Response Data Data will be summarised for dosed patients with measurable disease at baseline and sepa... | [
"Tumour Response Data",
"Derivation of tumour response variables",
"Percentage Best Change in TL",
"Duration of Response",
"PFS",
"ORR",
"Overall Survival"
] |
NCT03907969 | 9.4.2 | Safety analyses | 9.4.2 Safety analyses These are primary variables. All safety analyses will be performed on the safety analysis set. All patients who receive at least 1 dose of study treatment will be included in the assessment of the safety profile. At the end of the study, appropriate summaries of all safety data will be produced, a... | [
"ECG Changes"
] |
NCT03907969 | 9.4.3 | Other analyses | 9.4.3 Other analyses PK, PD, and biomarker research and pharmacogenetics exploratory analyses will be described in a separate document. The population PK analysis and PD analyses will be presented separately from the main CSR. | [] |
NCT03907969 | 9.4.3.1 | PK Analyses | 9.4.3.1 PK Analyses PK of AZD7648 is a secondary variable. The PK Analysis Set includes patients who have reportable plasma concentrations and PK parameters and who have no important protocol deviations or AEs that may impact on PK. Following single dose the following parameters maybe determined: Cmax, time to reach ma... | [
"Statistical Analysis Methods for Assessment of Pharmacokinetic Food Effect",
"COMBINATION MODULE 1 – AZD7648 AND PEGYLATED LIPOSOMAL DOXORUBICIN"
] |
NCT03907969 | 10 | PROTOCOL SUMMARY | 10 PROTOCOL SUMMARY | [] |
NCT03907969 | 10.1 | Schedule of Assessments – Combination Module 1 | 10.1 Schedule of Assessments – Combination Module 1 The SoA for the lead-in and on-treatment period for Combination Module 1 is shown in Table 13 below. Table 13 Schedule of assessments – Combination Module 1
Part A: | | Screening | | | Single Dose | | | | | | | Multiple Dose | | | | | IP | 28-day | Details | |-------... | [
"Part A:",
"Part B:"
] |
NCT03907969 | 11 | INTRODUCTION | 11 INTRODUCTION Combination Module 1 will investigate the safety, tolerability, and preliminary efficacy of AZD7648 administered in combination with PLD. | [] |
NCT03907969 | 11.1 | Study rationale | 11.1 Study rationale Doxorubicin is an inhibitor of topoisomerase-II that generates topoisomerase-DNA adducts and DSBs and used as a cancer therapy. PLD is FDA approved for treatment of ovarian cancer and multiple myeloma offering the same efficacy with less cardiotoxicity and haematotoxicity than the uncapsulated form... | [] |
NCT03907969 | 11.2 | Background | 11.2 Background As described in Section 2.2 the DNA-PK inhibitor AZD7648 is being developed as an anti-cancer therapy for patients with advanced malignancies. Combination Module 1 will investigate the safety, tolerability, PK, PD, and preliminary efficacy (anti-tumour activity) of AZD7648 in combination with PLD in pat... | [] |
NCT03907969 | 11.2.1 | Pegylated liposomal doxorubicin | 11.2.1 Pegylated liposomal doxorubicin | [] |
NCT03907969 | 11.2.1.1 | Overview of pegylated liposomal doxorubicin | 11.2.1.1 Overview of pegylated liposomal doxorubicin Doxorubicin is an inhibitor of topoisomerase 2 that generates topoisomerase-DNA adducts and DSBs and used as a cancer therapy. PLD has been approved by FDA and the European Medicines Agency for treatment of ovarian cancer and multiple myeloma offering the same effica... | [] |
NCT03907969 | 11.2.1.2 | Pegylated liposomal doxorubicin data | 11.2.1.2 Pegylated liposomal doxorubicin data
DOXIL® (FDA-approved): DOXIL is indicated for the treatment of patients with ovarian cancer whose disease has progressed or recurred after platinum-based chemotherapy. DOXIL was studied in 3 open-label, single-arm, clinical studies of 176 patients with metastatic ovarian c... | [
"DOXIL® (FDA-approved):",
"Caelyx (EMA-approved):",
"Preclinical data:"
] |
NCT03907969 | 11.3 | Benefit/risk assessment | 11.3 Benefit/risk assessment As described in Section 2.3 patients enrolled to this study have advanced cancer with a limited number of treatment options available, including chemotherapy such as PLD. The survival outcome and toxicity profile of chemotherapy in this setting mean that other active therapies are highly de... | [] |
NCT03907969 | 12 | STUDY DESIGN | 12 STUDY DESIGN | [] |
NCT03907969 | 12.1 | Overall design | 12.1 Overall design Combination Module 1 will evaluate the safety, tolerability, PK, PD, and preliminary efficacy (anti-tumour activity) of AZD7648 (given orally) in combination with PLD (given IV) as below: Part A: Dose escalation of AZD7648 in combination with PLD in approximately 30 evaluable patients with advanced ... | [] |
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