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This is a phase Ib, open-label, multicentre study of AZD1775 administered orally in monotherapy and in combination with carboplatin and paclitaxel to Asian patients with advanced solid tumours.
This is a phase Ib, open label, multicentre study of AZD1775 administered orally in monotherapy and in combination with carboplatin and paclitaxel in Asian patients with advanced solid tumours. The study design allows escalation or de-escalation of AZD1775 in combination with carboplatin and paclitaxel with intensive safety monitoring to ensure the safety of the patients. Approximately 12 evaluable patients will be enrolled in the dose-finding portion of this study. The total number of patients will depend upon the number of combination dose level evaluations necessary to define the recommended dose for further clinical evaluation. The proposed combination doses are : Dose level-1; Dose level 1; Dose level 2 (if Dose Level 1 tolerated). All combination doses other than Combination Dose level 1 may be subject to change by the SRC in light of emerging data. At least 3 and up to 6 evaluable patients will be required for each dose finding cohort. Once the recommended dose for further clinical evaluation is established, additional 3 to 6 patients may be enrolled to the cohort where the recommended dose has been defined to further characterise the safety, tolerability, pharmacokinetics, and efficacy profiles of AZD1775 in combination with paclitaxel and carboplatin. If this dose is subsequently found to be non-tolerated, alternative doses and/or schedules may be explored. This will be determined by the SRC.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| AZD1775 | Experimental | AZD1775 will be administered orally as a single dose on Day 1 Cycle 0. Following a 5±2 days washout period, AZD1775 (5 doses BID over 2.5 days) will be taken in combination with paclitaxel and carboplatin in each 21-day cycle for 6 cycles. Following 6 cycles of combination treatment, patients may continue on AZD1775 monotherapy (5 doses BID Day 1 to Day 2.5 in each 21-day cycle) at the investigator's discretion. |
|
| Paclitaxel | Experimental | Commercially available paclitaxel will be administered at a dosage of 175 mg/m2 as a 3-hour IV infusion on Cycle Day 1 of a 21-day cycle for 6 cycles. |
|
| Carboplatin | Experimental | Following the paclitaxel infusion, carboplatin will be administered at a dose of AUC 5 as an IV infusion on Cycle Day 1 of a 21-day cycle for 6 cycles. According to the Cancer Therapy Evaluation Program Information Letter Regarding the AUC Based Dosing of Carboplatin, the maximum carboplatin dose should not exceed the target AUC (mg*min/mL)*150 mL/min, but it may be less (Ivy et al 2010). For this study, the maximum dose of carboplatin cannot exceed a total dose of 750 mg. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| AZD1775 | Drug | AZD1775 is a highly selective, adenosine-triphosphate (ATP) competitive, small-molecule inhibitor of the WEE1 kinase that sensitizes tumour cells to cytotoxic agents and is being developed for the treatment of advanced solid tumours and p53 pathway deficient malignancies. Gemcitabine is a nucleoside analog used as chemotherapy. |
| Measure | Description | Time Frame |
|---|---|---|
| Number of Patients With Treatment-Emergent Adverse Events | The number of patients with treatment-emergent adverse events was analyzed on the safety analysis set which was comprised of all patients who received at least one dose of the investigational drug. | Up to 21 days (1 Cycle) |
| Number of Treatment-Emergent Adverse Events (TEAE) | The number of treatment-emergent adverse events was counted in the safety analysis set which was comprised of all patients who received at least one dose of the investigational drug. | Up to 21 days (1 Cycle) |
| Number of Patients With Treatment-Emergent Adverse Events During AZD1775 Monotherapy Cycle by System Organ Class and Preferred Term | The number of patients with TEAEs during AZD1775 Monotherapy Cycle was analyzed in the safety analysis set which was comprised of all patients who received at least one dose of the investigational drug. | Up to 1 week |
| Number of Patients With Clinically Important Changes in Haematology and Coagulation TEAEs by System Organ Class and Preferred Term | The number of patients with clinically important changes in haematology and coagulation TEAEs was analyzed in the safety analysis set which was comprised of all patients who received at least one dose of the investigational drug. | Up to 21 days (1 Cycle) |
| Number of Patients With Clinically Important Abnormalities in Clinical Chemistry by Preferred Term | The number of patients with clinically important changes in clinical chemistry TEAEs was analyzed in the safety analysis set which was comprised of all patients who received at least one dose of the investigational drug. | Up to 21 days (1 Cycle) |
| Measure | Description | Time Frame |
|---|---|---|
| Best Overall Response | The number of subjects with best overall response in CR, PR, NE, SD, PD subcategory. Best overall response is calculated based on the overall visit responses from each RECIST assessment. | Up to 18 months |
| Number of Patients With an Objective Response |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Dr. Paul De Souza, MD | Liverpool Hospital, New South Wales | Principal Investigator |
| Dr. Jason Lickliter, MD | Nucleus Network Limited, Victoria | Principal Investigator |
| Dr. Noboru Yamamoto, MD | NCC Hospital | Principal Investigator |
| Dr Toshihiko Doi, MD | NCC Hospital (East) | Principal Investigator |
| Prof Yung Ju Bang | Seoul National University Hospital | Principal Investigator |
| Prof Sang Prof Sang | Asan Medical Centre | Principal Investigator |
| Prof Keunchil Park | Samsung Medical Centre | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Research Site | Liverpool | 2170 | Australia | |||
| Research Site |
Total 21 subjects were consented to participate in the study. One (1) subject was screen failure, and one (1) other subject withdrew prior to treatment; Nineteen (19) subjects received treatment under the protocol.
The study was conducted at 7 clinical investigational sites located in Australia (2), Japan (2), and South Korea (3). A total of 21 subjects consented and 19 were enrolled between January 14, 2015 and June 13, 2016.
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| ID | Title | Description |
|---|---|---|
| FG000 | Cohort 1 | Subjects in Cohort 1 received a single oral dose of 175 mg of AZD1775 monotherapy followed 5 ± 2 days later by combination therapy consisting of 5 oral doses of 175 mg AZD1775 given 12 hours apart on days 1, 2, and 3 and single doses of intravenous paclitaxel (175 mg/m²) and intravenous carboplatin (AUC 5) given on day 1 of 21 day cycles. |
| FG001 | Cohort 1a | Subjects in Cohort 1a received a single oral dose of 175 mg of AZD1775 monotherapy followed 5 ± 2 days later by combination therapy consisting of 5 oral doses of 175 mg AZD1775 given 12 hours apart on days 1, 2, and 3 and single doses of intravenous carboplatin (AUC 5) given on day 1 of 21 day cycles. |
| FG002 | Cohort 2 | Subjects in Cohort 2 received a single oral dose of 225 mg of AZD1775 monotherapy followed 5 ± 2 days later by combination therapy consisting of 5 oral doses of 225 mg AZD1775 given 12 hours apart on days 1, 2, and 3 and single doses of intravenous paclitaxel (175 mg/m²) and intravenous carboplatin (AUC 5) given on day 1 of 21 day cycles. |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
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The Baseline Analysis Population is comprised of all participants who received at least one dose of study drug.
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| ID | Title | Description |
|---|---|---|
| BG000 | Cohort 1 | Subjects in Cohort 1 received a single oral dose of 175 mg of AZD1775 monotherapy followed 5 ± 2 days later by combination therapy consisting of 5 oral doses of 175 mg AZD1775 given 12 hours apart on days 1, 2, and 3 and single doses of intravenous paclitaxel (175 mg/m²) and intravenous carboplatin (AUC 5) given on day 1 of 21 day cycles. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Number of Patients With Treatment-Emergent Adverse Events | The number of patients with treatment-emergent adverse events was analyzed on the safety analysis set which was comprised of all patients who received at least one dose of the investigational drug. | All patients who received at least one dose of the investigational drug. | Posted | Number | Participants | Up to 21 days (1 Cycle) |
|
Up to 18 months.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Cohort 1 | Subjects in Cohort 1 received a single oral dose of 175 mg of AZD1775 monotherapy followed 5 ± 2 days later by combination therapy consisting of 5 oral doses of 175 mg AZD1775 given 12 hours apart on days 1, 2, and 3 and single doses of intravenous paclitaxel (175 mg/m²) and intravenous carboplatin (AUC 5) given on day 1 of 21 day cycles. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Febrile neutropenia | Blood and lymphatic system disorders | MedDRA Version 19.1 | Non-systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anaemia | Blood and lymphatic system disorders | MedDRA Version 19.1 | Non-systematic Assessment |
In the secondary outcome measure Duration of Response for which data are reported as weeks (95% CI) several instances occurred where the 95% CI could not be calculated.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Lone Ottesen | AstraZeneca | 1-877-240-9479 | ClinicalTrialTransparency@astrazeneca.com |
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| ID | Term |
|---|---|
| C549567 | adavosertib |
| D017239 | Paclitaxel |
| D016190 | Carboplatin |
| ID | Term |
|---|---|
| D043823 | Taxoids |
| D043822 | Cyclodecanes |
| D003516 | Cycloparaffins |
| D006840 | Hydrocarbons, Alicyclic |
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|
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| Paclitaxel | Drug | Paclitaxel is a mitotic inhibitor used in cancer chemotherapy ; it and docetaxel represent the taxane family of drugs. |
|
| carboplatin | Drug | Carboplatin is a chemotherapy drug used against some forms of cancer (mainly ovarian carcinoma, lung, head and neck cancers as well as endometrial, esophageal, bladder, breast and cervical; central nervous system or germ cell tumors; osteogenic sarcoma, and as preparation for a stem cell or bone marrow transplant.). |
|
| Number of Patients With Clinically Important Abnormalities in Vital Signs by Preferred Term | The number of patients with clinically important changes in vital sign TEAEs was analyzed in the safety analysis set which was comprised of all patients who received at least one dose of the investigational drug. | Up to 21 days (1 Cycle) |
Objective response is defined as either a complete response or a partial response. |
| Up to 18 months |
| Percentage of Patients With an Objective Response | Objective response is defined as either a complete response or a partial response. | Up to 18 months |
| Number of Patients With Clinical Benefit | Clinical benefit is defined as achieving complete response, partial response, or stable disease. | Up to 18 months |
| Percentage of Patients With Clinical Benefit | Clinical benefit is defined as achieving complete response, partial response, or stable disease. | Up to 18 months |
| Duration of Response | The duration of response is defined as the time in weeks from the date of first documented overall response occurrence of CR or PR, (whichever was recorded first) to the earliest date that progressive disease/death was documented. If progression or death has not been documented, a patient's DoR was censored at the date of last tumour assessment. | Up to 18 months |
| Peak Plasma Concentration (Cmax) of AZD1775 Following Single Dose Administration of AZD1775 Monotherapy | PK Samples collected in all treatment groups on Cycle 0 Day 1, Cycle 1 Day 1, and Cycle 1 Day 3 before the first (morning) dose of AZD1775 (predose) and at 1, 2, 4, 6, and 8 hours postdose |
| Time to Maximum Plasma Concentration (Tmax) of AZD1775 Following Single Dose Administration of AZD1775 Monotherapy | PK Samples will be collected in all treatment groups on Cycle 0 Day 1, Cycle 1 Day 1, and Cycle 1 Day 3 before the first (morning) dose of AZD1775 (predose) and at 1, 2, 4, 6, and 8 hours postdose |
| Area Under the Plasma Concentration-time Curve From Zero to the Time of the Last Measurable Concentration (AUC0-t) Following Single Dose Administration of AZD1775 Monotherapy | PK Samples will be collected in all treatment groups on Cycle 0 Day 1, Cycle 1 Day 1, and Cycle 1 Day 3 before the first (morning) dose of AZD1775 (predose) and at 1, 2, 4, 6, and 8 hours postdose |
| Plasma Concentration of AZD1775 8 Hours After Single Dose Administration (C8h) of AZD1775 Monotherapy | PK Samples will be collected in all treatment groups on Cycle 0 Day 1, Cycle 1 Day 1, and Cycle 1 Day 3 before the first (morning) dose of AZD1775 (predose) and at 1, 2, 4, 6, and 8 hours postdose |
| Peak Plasma Concentration (Cmax) of AZD1775 Following Oral Dose of AZD1775 in Combination With IV Infusion of Paclitaxel and Carboplatin (Cohorts 1 and 2) or Carboplatin Alone (Cohort 1a) | AZ1775:C0D1, C1D1, & C1D3 before AZD1775 dose and at 1,2,4,6&8 hrs postdose. Paclitaxel:C1D1 before paclitaxel infusion & at 1.5,3,4,6&8 hrs after start of infusion Carboplatin:C1D1 before carboplatin infusion &at 1,2,4,6&8 hrs after start of infusion |
| Time to Maximum Plasma Concentration (Tmax) of AZD1775 Following Single Dose of AZD1775 in Combination With IV Paclitaxel and Carboplatin (Cohorts 1 and 2) or Carboplatin Alone (Cohort 1a) | AZ1775:C0D1, C1D1, & C1D3 before AZD1775 dose and at 1,2,4,6&8 hrs postdose. Paclitaxel:C1D1 before paclitaxel infusion & at 1.5,3,4,6&8 hrs after start of infusion Carboplatin:C1D1 before carboplatin infusion &at 1,2,4,6&8 hrs after start of infusion |
| Area Under the Plasma Concentration-time Curve From Zero to the Time of the Last Measurable Concentration (AUC0-t) Following Single Dose of AZD1775 in Combination With IV Paclitaxel and Carboplatin (Cohorts 1 and 2) or Carboplatin Alone (Cohort 1a) | AZ1775:C0D1, C1D1, & C1D3 before AZD1775 dose and at 1,2,4,6&8 hrs postdose. Paclitaxel:C1D1 before paclitaxel infusion & at 1.5,3,4,6&8 hrs after start of infusion Carboplatin:C1D1 before carboplatin infusion &at 1,2,4,6&8 hrs after start of infusion |
| Plasma Concentration of AZD1775 8 Hours After Single Dose Administration (C8h) of AZD1775 in Combination With IV Paclitaxel and Carboplatin (Cohorts 1 and 2) or Carboplatin Alone (Cohort 1a) | AZ1775:C0D1, C1D1, & C1D3 before AZD1775 dose and at 1,2,4,6&8 hrs postdose. Paclitaxel:C1D1 before paclitaxel infusion & at 1.5,3,4,6&8 hrs after start of infusion Carboplatin:C1D1 before carboplatin infusion &at 1,2,4,6&8 hrs after start of infusion |
| Peak Plasma Concentration (Cmax) of AZD1775 at Steady State When Given in Combination With IV Infusion of Paclitaxel and Carboplatin (Cohorts 1 and 2) or Carboplatin Alone (Cohort 1a) | AZ1775:C0D1, C1D1, & C1D3 before AZD1775 dose and at 1,2,4,6&8 hrs postdose. Paclitaxel:C1D1 before paclitaxel infusion & at 1.5,3,4,6&8 hrs after start of infusion Carboplatin:C1D1 before carboplatin infusion &at 1,2,4,6&8 hrs after start of infusion |
| Time to Maximum Plasma Concentration (Tmax) of AZD1775 at Steady State When Given in Combination With IV Paclitaxel and Carboplatin (Cohorts 1 and 2) or Carboplatin Alone (Cohort 1a) | AZ1775:C0D1, C1D1, & C1D3 before AZD1775 dose and at 1,2,4,6&8 hrs postdose. Paclitaxel:C1D1 before paclitaxel infusion & at 1.5,3,4,6&8 hrs after start of infusion Carboplatin:C1D1 before carboplatin infusion &at 1,2,4,6&8 hrs after start of infusion |
| Area Under the Plasma Concentration-time Curve From Zero to the Time of the Last Measurable Concentration (AUC0-t) at Steady State for AZD1775 in Combination With IV Paclitaxel and Carboplatin (Cohorts 1 and 2) or Carboplatin Alone (Cohort 1a) | AZ1775:C0D1, C1D1, & C1D3 before AZD1775 dose and at 1,2,4,6&8 hrs postdose. Paclitaxel:C1D1 before paclitaxel infusion & at 1.5,3,4,6&8 hrs after start of infusion Carboplatin:C1D1 before carboplatin infusion &at 1,2,4,6&8 hrs after start of infusion |
| Plasma Concentration of AZD1775 8 Hours After Administration (C8h) at Steady State in Combination With IV Paclitaxel and Carboplatin (Cohorts 1 and 2) or Carboplatin Alone (Cohort 1a) | AZ1775:C0D1, C1D1, & C1D3 before AZD1775 dose and at 1,2,4,6&8 hrs postdose. Paclitaxel:C1D1 before paclitaxel infusion & at 1.5,3,4,6&8 hrs after start of infusion Carboplatin:C1D1 before carboplatin infusion &at 1,2,4,6&8 hrs after start of infusion |
| Peak Plasma Concentration (Cmax) of Paclitaxel Following Single IV Infusion in Combination With Single Dose Oral AZD1775 and IV Carboplatin | AZ1775:C0D1, C1D1, & C1D3 before AZD1775 dose and at 1,2,4,6&8 hrs postdose. Paclitaxel:C1D1 before paclitaxel infusion & at 1.5,3,4,6&8 hrs after start of infusion Carboplatin:C1D1 before carboplatin infusion &at 1,2,4,6&8 hrs after start of infusion |
| Area Under the Plasma Concentration-time Curve (AUC0-t) of Paclitaxel Following Single IV Infusion in Combination With Single Dose Oral AZD1775 and IV Carboplatin | AZ1775:C0D1, C1D1, & C1D3 before AZD1775 dose and at 1,2,4,6&8 hrs postdose. Paclitaxel:C1D1 before paclitaxel infusion & at 1.5,3,4,6&8 hrs after start of infusion Carboplatin:C1D1 before carboplatin infusion &at 1,2,4,6&8 hrs after start of infusion |
| Plasma Concentration of Paclitaxel at the End of Infusion (Ceoi) When Given Combination With Oral AZD1775 and IV Carboplatin. | AZ1775:C0D1, C1D1, & C1D3 before AZD1775 dose and at 1,2,4,6&8 hrs postdose. Paclitaxel:C1D1 before paclitaxel infusion & at 1.5,3,4,6&8 hrs after start of infusion Carboplatin:C1D1 before carboplatin infusion &at 1,2,4,6&8 hrs after start of infusion |
| Time to Maximum Plasma Concentration (Tmax) of IV Paclitaxel When Given in Combination With Oral AZD1775 and IV Carboplatin | AZ1775:C0D1, C1D1, & C1D3 before AZD1775 dose and at 1,2,4,6&8 hrs postdose. Paclitaxel:C1D1 before paclitaxel infusion & at 1.5,3,4,6&8 hrs after start of infusion Carboplatin:C1D1 before carboplatin infusion &at 1,2,4,6&8 hrs after start of infusion |
| Time to Last Detectable Concentration (Tlast) of Paclitaxel When Given in Combination With Oral AZD1775 and IV Carboplatin | AZ1775:C0D1, C1D1, & C1D3 before AZD1775 dose and at 1,2,4,6&8 hrs postdose. Paclitaxel:C1D1 before paclitaxel infusion & at 1.5,3,4,6&8 hrs after start of infusion Carboplatin:C1D1 before carboplatin infusion &at 1,2,4,6&8 hrs after start of infusion |
| Peak Plasma Concentration (Cmax) of Platinum Following Single IV Infusion of Carboplatin Over 1 Hour in Combination With Single Oral Dose AZD1775 Alone (Cohort 1a) or With IV Paclitaxel (Cohorts 1 and 2) | AZ1775:C0D1, C1D1, & C1D3 before AZD1775 dose and at 1,2,4,6&8 hrs postdose. Paclitaxel:C1D1 before paclitaxel infusion & at 1.5,3,4,6&8 hrs after start of infusion Carboplatin:C1D1 before carboplatin infusion &at 1,2,4,6&8 hrs after start of infusion |
| Area Under Plasma Concentration-time Curve From 0 to Last Measurable Conc. (AUC0-t) of Platinum Following Single IV Infusion of Carboplatin Over 1 Hour in Combination With Single Oral Dose AZD1775 Alone (Cohort 1a) or With IV Paclitaxel (Cohorts 1 & 2) | AZ1775:C0D1, C1D1, & C1D3 before AZD1775 dose and at 1,2,4,6&8 hrs postdose. Paclitaxel:C1D1 before paclitaxel infusion & at 1.5,3,4,6&8 hrs after start of infusion Carboplatin:C1D1 before carboplatin infusion &at 1,2,4,6&8 hrs after start of infusion |
| Plasma Concentration of Platinum at the End of Infusion (Ceoi) When Given as a 1 Hour Infusion in Combination With Oral AZD1775 and IV Paclitaxel. | AZ1775:C0D1, C1D1, & C1D3 before AZD1775 dose and at 1,2,4,6&8 hrs postdose. Paclitaxel:C1D1 before paclitaxel infusion & at 1.5,3,4,6&8 hrs after start of infusion Carboplatin:C1D1 before carboplatin infusion &at 1,2,4,6&8 hrs after start of infusion |
| Time to Peak Plasma Concentration of Platinum (Tmax) When Given as a 1 Hour Infusion in Combination With Oral AZD1775 and IV Paclitaxel. | AZ1775:C0D1, C1D1, & C1D3 before AZD1775 dose and at 1,2,4,6&8 hrs postdose. Paclitaxel:C1D1 before paclitaxel infusion & at 1.5,3,4,6&8 hrs after start of infusion Carboplatin:C1D1 before carboplatin infusion &at 1,2,4,6&8 hrs after start of infusion |
| Time to Last Detectable Concentration of Platinum (Tlast) When Given as a 1 Hour Infusion in Combination With Oral AZD1775 and IV Paclitaxel. | AZ1775:C0D1, C1D1, & C1D3 before AZD1775 dose and at 1,2,4,6&8 hrs postdose. Paclitaxel:C1D1 before paclitaxel infusion & at 1.5,3,4,6&8 hrs after start of infusion Carboplatin:C1D1 before carboplatin infusion &at 1,2,4,6&8 hrs after start of infusion |
| Peak Plasma Concentration (Cmax) of Platinum Following Single IV Infusion of Carboplatin Over 2 Hours in Combination With Single Oral Dose AZD1775 Alone (Cohort 1a) or With IV Paclitaxel (Cohorts 1 and 2) | AZ1775:C0D1, C1D1, & C1D3 before AZD1775 dose and at 1,2,4,6&8 hrs postdose. Paclitaxel:C1D1 before paclitaxel infusion & at 1.5,3,4,6&8 hrs after start of infusion Carboplatin:C1D1 before carboplatin infusion &at 1,2,4,6&8 hrs after start of infusion |
| Area Under Plasma Concentration-time Curve From 0 to Last Measurable Conc. (AUC0-t) of Platinum Following Single IV Infusion of Carboplatin Over 2 Hours in Combination With Single Oral Dose AZD1775 Alone (Cohort 1a) or With IV Paclitaxel (Cohorts 1 & 2) | AZ1775:C0D1, C1D1, & C1D3 before AZD1775 dose and at 1,2,4,6&8 hrs postdose. Paclitaxel:C1D1 before paclitaxel infusion & at 1.5,3,4,6&8 hrs after start of infusion Carboplatin:C1D1 before carboplatin infusion &at 1,2,4,6&8 hrs after start of infusion |
| Plasma Concentration of Platinum at the End of Infusion (Ceoi) When Given as a 2 Hour Infusion in Combination With Oral AZD1775 and IV Paclitaxel. | AZ1775:C0D1, C1D1, & C1D3 before AZD1775 dose and at 1,2,4,6&8 hrs postdose. Paclitaxel:C1D1 before paclitaxel infusion & at 1.5,3,4,6&8 hrs after start of infusion Carboplatin:C1D1 before carboplatin infusion &at 1,2,4,6&8 hrs after start of infusion |
| Time to Peak Plasma Concentration of Platinum (Tmax) When Given as a 2 Hour Infusion in Combination With Oral AZD1775 and IV Paclitaxel. | AZ1775:C0D1, C1D1, & C1D3 before AZD1775 dose and at 1,2,4,6&8 hrs postdose. Paclitaxel:C1D1 before paclitaxel infusion & at 1.5,3,4,6&8 hrs after start of infusion Carboplatin:C1D1 before carboplatin infusion &at 1,2,4,6&8 hrs after start of infusion |
| Time to Last Detectable Concentration of Platinum (Tlast) When Given as a 2 Hour Infusion in Combination With Oral AZD1775 and IV Paclitaxel. | AZ1775:C0D1, C1D1, & C1D3 before AZD1775 dose and at 1,2,4,6&8 hrs postdose. Paclitaxel:C1D1 before paclitaxel infusion & at 1.5,3,4,6&8 hrs after start of infusion Carboplatin:C1D1 before carboplatin infusion &at 1,2,4,6&8 hrs after start of infusion |
| Melbourne |
| 3004 |
| Australia |
| Research Site | Kashiwa | 277-8577 | Japan |
| Research Site | Sapporo | 003-0804 | Japan |
| Research Site | Seoul | 03080 | South Korea |
| Research Site | Seoul | 05505 | South Korea |
| Research Site | Seoul | 135-710 | South Korea |
| Withdrawal by Subject |
|
| Moved to local access programme. |
|
| Physician Decision |
|
| BG001 |
| Cohort 1a |
Subjects in Cohort 1a received a single oral dose of 175 mg of AZD1775 monotherapy followed 5 ± 2 days later by combination therapy consisting of 5 oral doses of 175 mg AZD1775 given 12 hours apart on days 1, 2, and 3 and single doses of intravenous carboplatin (AUC 5) given on day 1 of 21 day cycles. |
| BG002 | Cohort 2 | Subjects in Cohort 2 received a single oral dose of 225 mg of AZD1775 monotherapy followed 5 ± 2 days later by combination therapy consisting of 5 oral doses of 225 mg AZD1775 given 12 hours apart on days 1, 2, and 3 and single doses of intravenous paclitaxel (175 mg/m²) and intravenous carboplatin (AUC 5) given on day 1 of 21 day cycles. |
| BG003 | Total | Total of all reporting groups |
| Participants |
|
| Age, Continuous | Mean | Standard Deviation | years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Race/Ethnicity, Customized | Count of Participants | Participants |
|
| Region of Enrollment | Number | Participants |
|
| Smoking History | Count of Participants | Participants |
|
| Cancer Diagnosis | Count of Participants | Participants |
|
| Type of Tobacco Product Used | Count of Participants | Participants |
|
| Cohort 1a |
Subjects in Cohort 1a received a single oral dose of 175 mg of AZD1775 monotherapy followed 5 ± 2 days later by combination therapy consisting of 5 oral doses of 175 mg AZD1775 given 12 hours apart on days 1, 2, and 3 and single doses of intravenous carboplatin (AUC 5) given on day 1 of 21 day cycles. |
| OG002 | Cohort 2 | Subjects in Cohort 2 received a single oral dose of 225 mg of AZD1775 monotherapy followed 5 ± 2 days later by combination therapy consisting of 5 oral doses of 225 mg AZD1775 given 12 hours apart on days 1, 2, and 3 and single doses of intravenous paclitaxel (175 mg/m²) and intravenous carboplatin (AUC 5) given on day 1 of 21 day cycles. |
|
|
| Primary | Number of Treatment-Emergent Adverse Events (TEAE) | The number of treatment-emergent adverse events was counted in the safety analysis set which was comprised of all patients who received at least one dose of the investigational drug. | All patients who received at least one dose of the investigational drug. | Posted | Number | TEAE | Up to 21 days (1 Cycle) |
|
|
|
| Primary | Number of Patients With Treatment-Emergent Adverse Events During AZD1775 Monotherapy Cycle by System Organ Class and Preferred Term | The number of patients with TEAEs during AZD1775 Monotherapy Cycle was analyzed in the safety analysis set which was comprised of all patients who received at least one dose of the investigational drug. | All patients who received at least one dose of the investigational drug. | Posted | Number | Participants | Up to 1 week |
|
|
|
| Primary | Number of Patients With Clinically Important Changes in Haematology and Coagulation TEAEs by System Organ Class and Preferred Term | The number of patients with clinically important changes in haematology and coagulation TEAEs was analyzed in the safety analysis set which was comprised of all patients who received at least one dose of the investigational drug. | All patients who received at least one dose of the investigational drug. | Posted | Number | Participants | Up to 21 days (1 Cycle) |
|
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| Primary | Number of Patients With Clinically Important Abnormalities in Clinical Chemistry by Preferred Term | The number of patients with clinically important changes in clinical chemistry TEAEs was analyzed in the safety analysis set which was comprised of all patients who received at least one dose of the investigational drug. | All patients who received at least one dose of the investigational drug. | Posted | Number | Participants | Up to 21 days (1 Cycle) |
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| Primary | Number of Patients With Clinically Important Abnormalities in Vital Signs by Preferred Term | The number of patients with clinically important changes in vital sign TEAEs was analyzed in the safety analysis set which was comprised of all patients who received at least one dose of the investigational drug. | All patients who received at least one dose of the investigational drug. | Posted | Number | Participants | Up to 21 days (1 Cycle) |
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| Secondary | Best Overall Response | The number of subjects with best overall response in CR, PR, NE, SD, PD subcategory. Best overall response is calculated based on the overall visit responses from each RECIST assessment. | Best overall response was analyzed in the Evaluable-for-Response set, comprised of all patients who received at least one dose of the investigational drug and who had measurable disease at baseline. | Posted | Number | Participants | Up to 18 months |
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| Secondary | Number of Patients With an Objective Response | Objective response is defined as either a complete response or a partial response. | Posted | Number | Participants | Up to 18 months |
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| Secondary | Percentage of Patients With an Objective Response | Objective response is defined as either a complete response or a partial response. | Posted | Number | 95% Confidence Interval | Percentage | Up to 18 months |
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| Secondary | Number of Patients With Clinical Benefit | Clinical benefit is defined as achieving complete response, partial response, or stable disease. | Posted | Number | Participants | Up to 18 months |
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| Secondary | Percentage of Patients With Clinical Benefit | Clinical benefit is defined as achieving complete response, partial response, or stable disease. | Posted | Number | 95% Confidence Interval | Percentage | Up to 18 months |
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| Secondary | Duration of Response | The duration of response is defined as the time in weeks from the date of first documented overall response occurrence of CR or PR, (whichever was recorded first) to the earliest date that progressive disease/death was documented. If progression or death has not been documented, a patient's DoR was censored at the date of last tumour assessment. | Posted | Median | 95% Confidence Interval | Weeks | Up to 18 months |
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| Secondary | Peak Plasma Concentration (Cmax) of AZD1775 Following Single Dose Administration of AZD1775 Monotherapy | The pharmacokinetic analysis set consisted of all dosed patients for whom an adequate PK profile was obtained. | Posted | Geometric Mean | Geometric Coefficient of Variation | nM | PK Samples collected in all treatment groups on Cycle 0 Day 1, Cycle 1 Day 1, and Cycle 1 Day 3 before the first (morning) dose of AZD1775 (predose) and at 1, 2, 4, 6, and 8 hours postdose |
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| Secondary | Time to Maximum Plasma Concentration (Tmax) of AZD1775 Following Single Dose Administration of AZD1775 Monotherapy | The pharmacokinetic analysis set consisted of all dosed patients for whom an adequate PK profile was obtained. | Posted | Median | Full Range | hours | PK Samples will be collected in all treatment groups on Cycle 0 Day 1, Cycle 1 Day 1, and Cycle 1 Day 3 before the first (morning) dose of AZD1775 (predose) and at 1, 2, 4, 6, and 8 hours postdose |
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| Secondary | Area Under the Plasma Concentration-time Curve From Zero to the Time of the Last Measurable Concentration (AUC0-t) Following Single Dose Administration of AZD1775 Monotherapy | The pharmacokinetic analysis set consisted of all dosed patients for whom an adequate PK profile was obtained. | Posted | Geometric Mean | Geometric Coefficient of Variation | nM*h | PK Samples will be collected in all treatment groups on Cycle 0 Day 1, Cycle 1 Day 1, and Cycle 1 Day 3 before the first (morning) dose of AZD1775 (predose) and at 1, 2, 4, 6, and 8 hours postdose |
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| Secondary | Plasma Concentration of AZD1775 8 Hours After Single Dose Administration (C8h) of AZD1775 Monotherapy | The pharmacokinetic analysis set consisted of all dosed patients for whom an adequate PK profile was obtained. | Posted | Geometric Mean | Geometric Coefficient of Variation | nM | PK Samples will be collected in all treatment groups on Cycle 0 Day 1, Cycle 1 Day 1, and Cycle 1 Day 3 before the first (morning) dose of AZD1775 (predose) and at 1, 2, 4, 6, and 8 hours postdose |
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| Secondary | Peak Plasma Concentration (Cmax) of AZD1775 Following Oral Dose of AZD1775 in Combination With IV Infusion of Paclitaxel and Carboplatin (Cohorts 1 and 2) or Carboplatin Alone (Cohort 1a) | The pharmacokinetic analysis set consisted of all dosed patients for whom an adequate PK profile was obtained. | Posted | Geometric Mean | Geometric Coefficient of Variation | nM | AZ1775:C0D1, C1D1, & C1D3 before AZD1775 dose and at 1,2,4,6&8 hrs postdose. Paclitaxel:C1D1 before paclitaxel infusion & at 1.5,3,4,6&8 hrs after start of infusion Carboplatin:C1D1 before carboplatin infusion &at 1,2,4,6&8 hrs after start of infusion |
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| Secondary | Time to Maximum Plasma Concentration (Tmax) of AZD1775 Following Single Dose of AZD1775 in Combination With IV Paclitaxel and Carboplatin (Cohorts 1 and 2) or Carboplatin Alone (Cohort 1a) | The pharmacokinetic analysis set consisted of all dosed patients for whom an adequate PK profile was obtained. | Posted | Median | Full Range | hours | AZ1775:C0D1, C1D1, & C1D3 before AZD1775 dose and at 1,2,4,6&8 hrs postdose. Paclitaxel:C1D1 before paclitaxel infusion & at 1.5,3,4,6&8 hrs after start of infusion Carboplatin:C1D1 before carboplatin infusion &at 1,2,4,6&8 hrs after start of infusion |
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| Secondary | Area Under the Plasma Concentration-time Curve From Zero to the Time of the Last Measurable Concentration (AUC0-t) Following Single Dose of AZD1775 in Combination With IV Paclitaxel and Carboplatin (Cohorts 1 and 2) or Carboplatin Alone (Cohort 1a) | The pharmacokinetic analysis set consisted of all dosed patients for whom an adequate PK profile was obtained. | Posted | Geometric Mean | Geometric Coefficient of Variation | nM*h | AZ1775:C0D1, C1D1, & C1D3 before AZD1775 dose and at 1,2,4,6&8 hrs postdose. Paclitaxel:C1D1 before paclitaxel infusion & at 1.5,3,4,6&8 hrs after start of infusion Carboplatin:C1D1 before carboplatin infusion &at 1,2,4,6&8 hrs after start of infusion |
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| Secondary | Plasma Concentration of AZD1775 8 Hours After Single Dose Administration (C8h) of AZD1775 in Combination With IV Paclitaxel and Carboplatin (Cohorts 1 and 2) or Carboplatin Alone (Cohort 1a) | The pharmacokinetic analysis set consisted of all dosed patients for whom an adequate PK profile was obtained. | Posted | Geometric Mean | Geometric Coefficient of Variation | nM | AZ1775:C0D1, C1D1, & C1D3 before AZD1775 dose and at 1,2,4,6&8 hrs postdose. Paclitaxel:C1D1 before paclitaxel infusion & at 1.5,3,4,6&8 hrs after start of infusion Carboplatin:C1D1 before carboplatin infusion &at 1,2,4,6&8 hrs after start of infusion |
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| Secondary | Peak Plasma Concentration (Cmax) of AZD1775 at Steady State When Given in Combination With IV Infusion of Paclitaxel and Carboplatin (Cohorts 1 and 2) or Carboplatin Alone (Cohort 1a) | The pharmacokinetic analysis set consisted of all dosed patients for whom an adequate PK profile was obtained. | Posted | Geometric Mean | Geometric Coefficient of Variation | nM | AZ1775:C0D1, C1D1, & C1D3 before AZD1775 dose and at 1,2,4,6&8 hrs postdose. Paclitaxel:C1D1 before paclitaxel infusion & at 1.5,3,4,6&8 hrs after start of infusion Carboplatin:C1D1 before carboplatin infusion &at 1,2,4,6&8 hrs after start of infusion |
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| Secondary | Time to Maximum Plasma Concentration (Tmax) of AZD1775 at Steady State When Given in Combination With IV Paclitaxel and Carboplatin (Cohorts 1 and 2) or Carboplatin Alone (Cohort 1a) | The pharmacokinetic analysis set consisted of all dosed patients for whom an adequate PK profile was obtained. | Posted | Median | Full Range | hours | AZ1775:C0D1, C1D1, & C1D3 before AZD1775 dose and at 1,2,4,6&8 hrs postdose. Paclitaxel:C1D1 before paclitaxel infusion & at 1.5,3,4,6&8 hrs after start of infusion Carboplatin:C1D1 before carboplatin infusion &at 1,2,4,6&8 hrs after start of infusion |
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| Secondary | Area Under the Plasma Concentration-time Curve From Zero to the Time of the Last Measurable Concentration (AUC0-t) at Steady State for AZD1775 in Combination With IV Paclitaxel and Carboplatin (Cohorts 1 and 2) or Carboplatin Alone (Cohort 1a) | The pharmacokinetic analysis set consisted of all dosed patients for whom an adequate PK profile was obtained. | Posted | Geometric Mean | Geometric Coefficient of Variation | nM*h | AZ1775:C0D1, C1D1, & C1D3 before AZD1775 dose and at 1,2,4,6&8 hrs postdose. Paclitaxel:C1D1 before paclitaxel infusion & at 1.5,3,4,6&8 hrs after start of infusion Carboplatin:C1D1 before carboplatin infusion &at 1,2,4,6&8 hrs after start of infusion |
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| Secondary | Plasma Concentration of AZD1775 8 Hours After Administration (C8h) at Steady State in Combination With IV Paclitaxel and Carboplatin (Cohorts 1 and 2) or Carboplatin Alone (Cohort 1a) | The pharmacokinetic analysis set consisted of all dosed patients for whom an adequate PK profile was obtained. | Posted | Geometric Mean | Geometric Coefficient of Variation | nM | AZ1775:C0D1, C1D1, & C1D3 before AZD1775 dose and at 1,2,4,6&8 hrs postdose. Paclitaxel:C1D1 before paclitaxel infusion & at 1.5,3,4,6&8 hrs after start of infusion Carboplatin:C1D1 before carboplatin infusion &at 1,2,4,6&8 hrs after start of infusion |
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| Secondary | Peak Plasma Concentration (Cmax) of Paclitaxel Following Single IV Infusion in Combination With Single Dose Oral AZD1775 and IV Carboplatin | The pharmacokinetic analysis set consisted of all dosed patients for whom an adequate PK profile was obtained. | Posted | Geometric Mean | Geometric Coefficient of Variation | ng/mL | AZ1775:C0D1, C1D1, & C1D3 before AZD1775 dose and at 1,2,4,6&8 hrs postdose. Paclitaxel:C1D1 before paclitaxel infusion & at 1.5,3,4,6&8 hrs after start of infusion Carboplatin:C1D1 before carboplatin infusion &at 1,2,4,6&8 hrs after start of infusion |
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| Secondary | Area Under the Plasma Concentration-time Curve (AUC0-t) of Paclitaxel Following Single IV Infusion in Combination With Single Dose Oral AZD1775 and IV Carboplatin | The pharmacokinetic analysis set consisted of all dosed patients for whom an adequate PK profile was obtained. | Posted | Geometric Mean | Geometric Coefficient of Variation | h*ng/mL | AZ1775:C0D1, C1D1, & C1D3 before AZD1775 dose and at 1,2,4,6&8 hrs postdose. Paclitaxel:C1D1 before paclitaxel infusion & at 1.5,3,4,6&8 hrs after start of infusion Carboplatin:C1D1 before carboplatin infusion &at 1,2,4,6&8 hrs after start of infusion |
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| Secondary | Plasma Concentration of Paclitaxel at the End of Infusion (Ceoi) When Given Combination With Oral AZD1775 and IV Carboplatin. | The pharmacokinetic analysis set consisted of all dosed patients for whom an adequate PK profile was obtained. | Posted | Geometric Mean | Geometric Coefficient of Variation | ng/mL | AZ1775:C0D1, C1D1, & C1D3 before AZD1775 dose and at 1,2,4,6&8 hrs postdose. Paclitaxel:C1D1 before paclitaxel infusion & at 1.5,3,4,6&8 hrs after start of infusion Carboplatin:C1D1 before carboplatin infusion &at 1,2,4,6&8 hrs after start of infusion |
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| Secondary | Time to Maximum Plasma Concentration (Tmax) of IV Paclitaxel When Given in Combination With Oral AZD1775 and IV Carboplatin | The pharmacokinetic analysis set consisted of all dosed patients for whom an adequate PK profile was obtained. | Posted | Median | Full Range | hours | AZ1775:C0D1, C1D1, & C1D3 before AZD1775 dose and at 1,2,4,6&8 hrs postdose. Paclitaxel:C1D1 before paclitaxel infusion & at 1.5,3,4,6&8 hrs after start of infusion Carboplatin:C1D1 before carboplatin infusion &at 1,2,4,6&8 hrs after start of infusion |
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| Secondary | Time to Last Detectable Concentration (Tlast) of Paclitaxel When Given in Combination With Oral AZD1775 and IV Carboplatin | The pharmacokinetic analysis set consisted of all dosed patients for whom an adequate PK profile was obtained. | Posted | Median | Full Range | hours | AZ1775:C0D1, C1D1, & C1D3 before AZD1775 dose and at 1,2,4,6&8 hrs postdose. Paclitaxel:C1D1 before paclitaxel infusion & at 1.5,3,4,6&8 hrs after start of infusion Carboplatin:C1D1 before carboplatin infusion &at 1,2,4,6&8 hrs after start of infusion |
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| Secondary | Peak Plasma Concentration (Cmax) of Platinum Following Single IV Infusion of Carboplatin Over 1 Hour in Combination With Single Oral Dose AZD1775 Alone (Cohort 1a) or With IV Paclitaxel (Cohorts 1 and 2) | The pharmacokinetic analysis set consisted of all dosed patients for whom an adequate PK profile was obtained. | Posted | Geometric Mean | Geometric Coefficient of Variation | ng/mL | AZ1775:C0D1, C1D1, & C1D3 before AZD1775 dose and at 1,2,4,6&8 hrs postdose. Paclitaxel:C1D1 before paclitaxel infusion & at 1.5,3,4,6&8 hrs after start of infusion Carboplatin:C1D1 before carboplatin infusion &at 1,2,4,6&8 hrs after start of infusion |
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| Secondary | Area Under Plasma Concentration-time Curve From 0 to Last Measurable Conc. (AUC0-t) of Platinum Following Single IV Infusion of Carboplatin Over 1 Hour in Combination With Single Oral Dose AZD1775 Alone (Cohort 1a) or With IV Paclitaxel (Cohorts 1 & 2) | The pharmacokinetic analysis set consisted of all dosed patients for whom an adequate PK profile was obtained. | Posted | Geometric Mean | Geometric Coefficient of Variation | h*ng/mL | AZ1775:C0D1, C1D1, & C1D3 before AZD1775 dose and at 1,2,4,6&8 hrs postdose. Paclitaxel:C1D1 before paclitaxel infusion & at 1.5,3,4,6&8 hrs after start of infusion Carboplatin:C1D1 before carboplatin infusion &at 1,2,4,6&8 hrs after start of infusion |
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| Secondary | Plasma Concentration of Platinum at the End of Infusion (Ceoi) When Given as a 1 Hour Infusion in Combination With Oral AZD1775 and IV Paclitaxel. | The pharmacokinetic analysis set consisted of all dosed patients for whom an adequate PK profile was obtained. | Posted | Geometric Mean | Geometric Coefficient of Variation | ng/mL | AZ1775:C0D1, C1D1, & C1D3 before AZD1775 dose and at 1,2,4,6&8 hrs postdose. Paclitaxel:C1D1 before paclitaxel infusion & at 1.5,3,4,6&8 hrs after start of infusion Carboplatin:C1D1 before carboplatin infusion &at 1,2,4,6&8 hrs after start of infusion |
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| Secondary | Time to Peak Plasma Concentration of Platinum (Tmax) When Given as a 1 Hour Infusion in Combination With Oral AZD1775 and IV Paclitaxel. | The pharmacokinetic analysis set consisted of all dosed patients for whom an adequate PK profile was obtained. | Posted | Median | Full Range | hours | AZ1775:C0D1, C1D1, & C1D3 before AZD1775 dose and at 1,2,4,6&8 hrs postdose. Paclitaxel:C1D1 before paclitaxel infusion & at 1.5,3,4,6&8 hrs after start of infusion Carboplatin:C1D1 before carboplatin infusion &at 1,2,4,6&8 hrs after start of infusion |
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| Secondary | Time to Last Detectable Concentration of Platinum (Tlast) When Given as a 1 Hour Infusion in Combination With Oral AZD1775 and IV Paclitaxel. | The pharmacokinetic analysis set consisted of all dosed patients for whom an adequate PK profile was obtained. | Posted | Median | Full Range | hours | AZ1775:C0D1, C1D1, & C1D3 before AZD1775 dose and at 1,2,4,6&8 hrs postdose. Paclitaxel:C1D1 before paclitaxel infusion & at 1.5,3,4,6&8 hrs after start of infusion Carboplatin:C1D1 before carboplatin infusion &at 1,2,4,6&8 hrs after start of infusion |
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| Secondary | Peak Plasma Concentration (Cmax) of Platinum Following Single IV Infusion of Carboplatin Over 2 Hours in Combination With Single Oral Dose AZD1775 Alone (Cohort 1a) or With IV Paclitaxel (Cohorts 1 and 2) | The pharmacokinetic analysis set consisted of all dosed patients for whom an adequate PK profile was obtained. | Posted | Geometric Mean | Geometric Coefficient of Variation | ng/mL | AZ1775:C0D1, C1D1, & C1D3 before AZD1775 dose and at 1,2,4,6&8 hrs postdose. Paclitaxel:C1D1 before paclitaxel infusion & at 1.5,3,4,6&8 hrs after start of infusion Carboplatin:C1D1 before carboplatin infusion &at 1,2,4,6&8 hrs after start of infusion |
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| Secondary | Area Under Plasma Concentration-time Curve From 0 to Last Measurable Conc. (AUC0-t) of Platinum Following Single IV Infusion of Carboplatin Over 2 Hours in Combination With Single Oral Dose AZD1775 Alone (Cohort 1a) or With IV Paclitaxel (Cohorts 1 & 2) | The pharmacokinetic analysis set consisted of all dosed patients for whom an adequate PK profile was obtained. | Posted | Geometric Mean | Geometric Coefficient of Variation | h*ng/mL | AZ1775:C0D1, C1D1, & C1D3 before AZD1775 dose and at 1,2,4,6&8 hrs postdose. Paclitaxel:C1D1 before paclitaxel infusion & at 1.5,3,4,6&8 hrs after start of infusion Carboplatin:C1D1 before carboplatin infusion &at 1,2,4,6&8 hrs after start of infusion |
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| Secondary | Plasma Concentration of Platinum at the End of Infusion (Ceoi) When Given as a 2 Hour Infusion in Combination With Oral AZD1775 and IV Paclitaxel. | The pharmacokinetic analysis set consisted of all dosed patients for whom an adequate PK profile was obtained. | Posted | Geometric Mean | Geometric Coefficient of Variation | ng/mL | AZ1775:C0D1, C1D1, & C1D3 before AZD1775 dose and at 1,2,4,6&8 hrs postdose. Paclitaxel:C1D1 before paclitaxel infusion & at 1.5,3,4,6&8 hrs after start of infusion Carboplatin:C1D1 before carboplatin infusion &at 1,2,4,6&8 hrs after start of infusion |
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| Secondary | Time to Peak Plasma Concentration of Platinum (Tmax) When Given as a 2 Hour Infusion in Combination With Oral AZD1775 and IV Paclitaxel. | The pharmacokinetic analysis set consisted of all dosed patients for whom an adequate PK profile was obtained. | Posted | Median | Full Range | hours | AZ1775:C0D1, C1D1, & C1D3 before AZD1775 dose and at 1,2,4,6&8 hrs postdose. Paclitaxel:C1D1 before paclitaxel infusion & at 1.5,3,4,6&8 hrs after start of infusion Carboplatin:C1D1 before carboplatin infusion &at 1,2,4,6&8 hrs after start of infusion |
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| Secondary | Time to Last Detectable Concentration of Platinum (Tlast) When Given as a 2 Hour Infusion in Combination With Oral AZD1775 and IV Paclitaxel. | The pharmacokinetic analysis set consisted of all dosed patients for whom an adequate PK profile was obtained. | Posted | Median | Full Range | hours | AZ1775:C0D1, C1D1, & C1D3 before AZD1775 dose and at 1,2,4,6&8 hrs postdose. Paclitaxel:C1D1 before paclitaxel infusion & at 1.5,3,4,6&8 hrs after start of infusion Carboplatin:C1D1 before carboplatin infusion &at 1,2,4,6&8 hrs after start of infusion |
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| 1 |
| 7 |
| 3 |
| 7 |
| 7 |
| 7 |
| EG001 | Cohort 1a | Subjects in Cohort 1a received a single oral dose of 175 mg of AZD1775 monotherapy followed 5 ± 2 days later by combination therapy consisting of 5 oral doses of 175 mg AZD1775 given 12 hours apart on days 1, 2, and 3 and single doses of intravenous carboplatin (AUC 5) given on day 1 of 21 day cycles. | 1 | 6 | 0 | 6 | 6 | 6 |
| EG002 | Cohort 2 | Subjects in Cohort 2 received a single oral dose of 225 mg of AZD1775 monotherapy followed 5 ± 2 days later by combination therapy consisting of 5 oral doses of 225 mg AZD1775 given 12 hours apart on days 1, 2, and 3 and single doses of intravenous paclitaxel (175 mg/m²) and intravenous carboplatin (AUC 5) given on day 1 of 21 day cycles. | 1 | 6 | 4 | 6 | 6 | 6 |
| Neutropenia | Blood and lymphatic system disorders | MedDRA Version 19.1 | Non-systematic Assessment |
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| Diarrhoea | Gastrointestinal disorders | MedDRA Version 19.1 | Non-systematic Assessment |
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| Nausea | Gastrointestinal disorders | MedDRA Version 19.1 | Non-systematic Assessment |
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| Vomiting | Gastrointestinal disorders | MedDRA Version 19.1 | Non-systematic Assessment |
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| Sepsis | Infections and infestations | MedDRA Version 19.1 | Non-systematic Assessment |
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| Clostridium difficile colitis | Infections and infestations | MedDRA Version 19.1 | Non-systematic Assessment |
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| Pyrexia | General disorders | MedDRA Version 19.1 | Non-systematic Assessment |
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| Hepatic function abnormal | Hepatobiliary disorders | MedDRA Version 19.1 | Non-systematic Assessment |
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| Platelet count decreased | Investigations | MedDRA Version 19.1 | Non-systematic Assessment |
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| Acute respiratory distress syndrome | Respiratory, thoracic and mediastinal disorders | MedDRA Version 19.1 | Non-systematic Assessment |
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| Hypotension | Vascular disorders | MedDRA Version 19.1 | Non-systematic Assessment |
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| Neutropenia | Blood and lymphatic system disorders | MedDRA Version 19.1 | Non-systematic Assessment |
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| Thrombocytopenia | Blood and lymphatic system disorders | MedDRA Version 19.1 | Non-systematic Assessment |
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| Febrile Neutropenia | Blood and lymphatic system disorders | MedDRA Version 19.1 | Non-systematic Assessment |
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| Eyelid Oedema | Eye disorders | MedDRA Version 19.1 | Non-systematic Assessment |
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| Nausea | Gastrointestinal disorders | MedDRA Version 19.1 | Non-systematic Assessment |
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| Abdominal pain upper | Gastrointestinal disorders | MedDRA Version 19.1 | Non-systematic Assessment |
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| Constipation | Gastrointestinal disorders | MedDRA Version 19.1 | Non-systematic Assessment |
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| Diarrhoea | Gastrointestinal disorders | MedDRA Version 19.1 | Non-systematic Assessment |
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| Abdominal distension | Gastrointestinal disorders | MedDRA Version 19.1 | Non-systematic Assessment |
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| Abdominal pain | Gastrointestinal disorders | MedDRA Version 19.1 | Non-systematic Assessment |
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| Dyspepsia | Gastrointestinal disorders | MedDRA Version 19.1 | Non-systematic Assessment |
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| Vomiting | Gastrointestinal disorders | MedDRA Version 19.1 | Non-systematic Assessment |
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| Oesphageal disorder | Gastrointestinal disorders | MedDRA Version 19.1 | Non-systematic Assessment |
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| Ileus | Gastrointestinal disorders | MedDRA Version 19.1 | Non-systematic Assessment |
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| Dysphagia | Gastrointestinal disorders | MedDRA Version 19.1 | Non-systematic Assessment |
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| Proctologia | Gastrointestinal disorders | MedDRA Version 19.1 | Non-systematic Assessment |
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| Intestinal obstruction | Gastrointestinal disorders | MedDRA Version 19.1 | Non-systematic Assessment |
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| Gingival pain | Gastrointestinal disorders | MedDRA Version 19.1 | Non-systematic Assessment |
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| Anal Haemorrhage | Gastrointestinal disorders | MedDRA Version 19.1 | Non-systematic Assessment |
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| Oedema | General disorders | MedDRA Version 19.1 | Non-systematic Assessment |
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| Fatugue | General disorders | MedDRA Version 19.1 | Non-systematic Assessment |
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| Gait disturbance | General disorders | MedDRA Version 19.1 | Non-systematic Assessment |
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| Pyrexia | General disorders | MedDRA Version 19.1 | Non-systematic Assessment |
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| Asthenia | General disorders | MedDRA Version 19.1 | Non-systematic Assessment |
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| Chills | General disorders | MedDRA Version 19.1 | Non-systematic Assessment |
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| Chest pain | General disorders | MedDRA Version 19.1 | Non-systematic Assessment |
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| Malaise | General disorders | MedDRA Version 19.1 | Non-systematic Assessment |
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| Hypersensitivity | Immune system disorders | MedDRA Version 19.1 | Non-systematic Assessment |
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| Herpes zoster | Infections and infestations | MedDRA Version 19.1 | Non-systematic Assessment |
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| Liver abscess | Infections and infestations | MedDRA Version 19.1 | Non-systematic Assessment |
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| Cystitis | Infections and infestations | MedDRA Version 19.1 | Non-systematic Assessment |
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| Bone abscess | Infections and infestations | MedDRA Version 19.1 | Non-systematic Assessment |
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| Urinary tract infection | Infections and infestations | MedDRA Version 19.1 | Non-systematic Assessment |
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| Anal infection | Infections and infestations | MedDRA Version 19.1 | Non-systematic Assessment |
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| Herpes simplex | Infections and infestations | MedDRA Version 19.1 | Non-systematic Assessment |
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| Fallopian tube abscess | Infections and infestations | MedDRA Version 19.1 | Non-systematic Assessment |
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| Postoperative wound complication | Injury, poisoning and procedural complications | MedDRA Version 19.1 | Non-systematic Assessment |
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| Radiation skin injury | Injury, poisoning and procedural complications | MedDRA Version 19.1 | Non-systematic Assessment |
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| Rash | Injury, poisoning and procedural complications | MedDRA Version 19.1 | Non-systematic Assessment |
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| Postoperative pain | Injury, poisoning and procedural complications | MedDRA Version 19.1 | Non-systematic Assessment |
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| Blood lactate dehydrogenase increased | Investigations | MedDRA Version 19.1 | Non-systematic Assessment |
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| C-reactive protein increased | Investigations | MedDRA Version 19.1 | Non-systematic Assessment |
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| Hematocrit decreased | Investigations | MedDRA Version 19.1 | Non-systematic Assessment |
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| Monocyte count decreased | Investigations | MedDRA Version 19.1 | Non-systematic Assessment |
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| Platelet count decreased | Investigations | MedDRA Version 19.1 | Non-systematic Assessment |
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| White blood cell count decreased | Investigations | MedDRA Version 19.1 | Non-systematic Assessment |
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| Blood alklaine phosphatase increased | Investigations | MedDRA Version 19.1 | Non-systematic Assessment |
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| Neutrophil count decreased | Investigations | MedDRA Version 19.1 | Non-systematic Assessment |
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| Aspartate aminotransferase increased | Investigations | MedDRA Version 19.1 | Non-systematic Assessment |
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| Alanine aminotransferase increased | Investigations | MedDRA Version 19.1 | Non-systematic Assessment |
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| Decreased appetite | Metabolism and nutrition disorders | MedDRA Version 19.1 | Non-systematic Assessment |
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| Hyperglycaemia | Metabolism and nutrition disorders | MedDRA Version 19.1 | Non-systematic Assessment |
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| Hypoalbuminemia | Metabolism and nutrition disorders | MedDRA Version 19.1 | Non-systematic Assessment |
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| Hypomagnesaemia | Metabolism and nutrition disorders | MedDRA Version 19.1 | Non-systematic Assessment |
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| Dehydration | Metabolism and nutrition disorders | MedDRA Version 19.1 | Non-systematic Assessment |
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| Hypocalcaemia | Metabolism and nutrition disorders | MedDRA Version 19.1 | Non-systematic Assessment |
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| Hypokalemia | Metabolism and nutrition disorders | MedDRA Version 19.1 | Non-systematic Assessment |
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| Hyponatremia | Metabolism and nutrition disorders | MedDRA Version 19.1 | Non-systematic Assessment |
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| Hypophosphatemia | Metabolism and nutrition disorders | MedDRA Version 19.1 | Non-systematic Assessment |
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| Hypercalcemia | Metabolism and nutrition disorders | MedDRA Version 19.1 | Non-systematic Assessment |
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| Hypercholesterolemia | Metabolism and nutrition disorders | MedDRA Version 19.1 | Non-systematic Assessment |
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| Back pain | Musculoskeletal and connective tissue disorders | MedDRA Version 19.1 | Non-systematic Assessment |
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| Myalgia | Musculoskeletal and connective tissue disorders | MedDRA Version 19.1 | Non-systematic Assessment |
|
| Pain in extremity | Musculoskeletal and connective tissue disorders | MedDRA Version 19.1 | Non-systematic Assessment |
|
| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA Version 19.1 | Non-systematic Assessment |
|
| Muscle spasms | Musculoskeletal and connective tissue disorders | MedDRA Version 19.1 | Non-systematic Assessment |
|
| Flank pain | Musculoskeletal and connective tissue disorders | MedDRA Version 19.1 | Non-systematic Assessment |
|
| Musculoskeletal pain | Musculoskeletal and connective tissue disorders | MedDRA Version 19.1 | Non-systematic Assessment |
|
| Low back pain | Musculoskeletal and connective tissue disorders | MedDRA Version 19.1 | Non-systematic Assessment |
|
| Lethargy | Nervous system disorders | MedDRA Version 19.1 | Non-systematic Assessment |
|
| Neuralgia | Nervous system disorders | MedDRA Version 19.1 | Non-systematic Assessment |
|
| Peripheral sensory neuropathy | Nervous system disorders | MedDRA Version 19.1 | Non-systematic Assessment |
|
| Peripheral neuropathy | Nervous system disorders | MedDRA Version 19.1 | Non-systematic Assessment |
|
| Headache | Nervous system disorders | MedDRA Version 19.1 | Non-systematic Assessment |
|
| Dizziness | Nervous system disorders | MedDRA Version 19.1 | Non-systematic Assessment |
|
| Akathisia | Nervous system disorders | MedDRA Version 19.1 | Non-systematic Assessment |
|
| Tumour pain | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA Version 19.1 | Non-systematic Assessment |
|
| Anxiety | Psychiatric disorders | MedDRA Version 19.1 | Non-systematic Assessment |
|
| Insomnia | Psychiatric disorders | MedDRA Version 19.1 | Non-systematic Assessment |
|
| Azotemia | Renal and urinary disorders | MedDRA Version 19.1 | Non-systematic Assessment |
|
| Micturition urgency | Renal and urinary disorders | MedDRA Version 19.1 | Non-systematic Assessment |
|
| Chromaturia | Renal and urinary disorders | MedDRA Version 19.1 | Non-systematic Assessment |
|
| Vaginal haemorrhage | Reproductive system and breast disorders | MedDRA Version 19.1 | Non-systematic Assessment |
|
| Pleural effusion | Respiratory, thoracic and mediastinal disorders | MedDRA Version 19.1 | Non-systematic Assessment |
|
| Oropharyngeal discomfort | Respiratory, thoracic and mediastinal disorders | MedDRA Version 19.1 | Non-systematic Assessment |
|
| Productive cough | Respiratory, thoracic and mediastinal disorders | MedDRA Version 19.1 | Non-systematic Assessment |
|
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA Version 19.1 | Non-systematic Assessment |
|
| Sputum increased | Respiratory, thoracic and mediastinal disorders | MedDRA Version 19.1 | Non-systematic Assessment |
|
| Pneumothorax | Respiratory, thoracic and mediastinal disorders | MedDRA Version 19.1 | Non-systematic Assessment |
|
| Alopecia | Skin and subcutaneous tissue disorders | MedDRA Version 19.1 | Non-systematic Assessment |
|
| Pruritus | Skin and subcutaneous tissue disorders | MedDRA Version 19.1 | Non-systematic Assessment |
|
| Ingrown nail | Skin and subcutaneous tissue disorders | MedDRA Version 19.1 | Non-systematic Assessment |
|
| Vascular skin disorder | Skin and subcutaneous tissue disorders | MedDRA Version 19.1 | Non-systematic Assessment |
|
| Dry skin | Skin and subcutaneous tissue disorders | MedDRA Version 19.1 | Non-systematic Assessment |
|
| Pruritus generalised | Skin and subcutaneous tissue disorders | MedDRA Version 19.1 | Non-systematic Assessment |
|
| Hyperhydrosis | Skin and subcutaneous tissue disorders | MedDRA Version 19.1 | Non-systematic Assessment |
|
| Oophorectomy | Surgical and medical procedures | MedDRA Version 19.1 | Non-systematic Assessment |
|
| Hypotension | Vascular disorders | MedDRA Version 19.1 | Non-systematic Assessment |
|
| Arteriosclerosis | Vascular disorders | MedDRA Version 19.1 | Non-systematic Assessment |
|
Not provided
Not provided
| D006844 |
| Hydrocarbons, Cyclic |
| D006838 | Hydrocarbons |
| D009930 | Organic Chemicals |
| D004224 | Diterpenes |
| D013729 | Terpenes |
| D056831 | Coordination Complexes |
|
| Number of TEAEs Related to Study Treatment |
|
| Number of Serious TEAEs |
|
| Number of Severe TEAEs |
|
| Number of TEAEs with AZD1775 discontinued |
|
| Number of TEAEs with paclitaxel discontinued |
|
| Number of TEAEs with carboplatin discontinued |
|
| Number of TEAEs with fatal outcome |
|
| Number of Dose-Limiting Toxicities (DLT) |
|
| Number of TEAEs with DLT |
|
|
| Gastrointestinal Disorders - Constipation |
|
| Gastrointestinal Disorders - Diarrhoea |
|
| Immune System Disorders - Hypersensitivity |
|
|
| BLSD - Thrombocytopenia |
|
| BLSD - Febrile Neutropenia |
|
| Investigations - WBC Count Decreased |
|
| Investigations - Neutrophil Count Decreased |
|
| Investigations - Platelet Count Decreased |
|
| Investigations - Haematocrit Decreased |
|
| Investigations - Monocyte Count Decreased |
|
|
| Blood alkaline phosphatase increased |
|
| Blood lactate dehydrogenase increased |
|
| C-reactive protein increased |
|
| Hypoalbuminemia |
|
| Hypokalemia |
|
| Hypophosphatemia |
|
| Dehydration |
|
| Hyperglycaemia |
|
| Hypocalcaemia |
|
| Hyponatraemia |
|
| Hypercalcaemia |
|
| Hypercholsterolaemia |
|
| Hypoglycaemia |
|
| Hypomagnesaemia |
|
| Azotemia |
|
| Hepatic function abnormal |
|
| Title | Measurements |
|---|---|
|
| Title | Measurements |
|---|---|
|
| Stable Disease |
|
| Progressive Disease |
|
| Complete Response |
|