Phase 1
Completed N=19
Phase Ib Study AZD1775 in Combination With Carboplatin and Paclitaxel in Adult Asian Patients With Solid Tumours
Advanced Solid Tumours
Source: ClinicalTrials.gov NCT02341456 ↗
Enrolled (actual)
19
Serious AEs
36.8%
Results posted
Mar 2019
Primary outcomePrimary: Number of Patients With Treatment-Emergent Adverse Events — 7; 6; 6; 6 Participants
Summary
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.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Number of Patients With Treatment-Emergent Adverse Events |
7; 6; 6; 6; 6; 6 | — |
| PRIMARY Number of Treatment-Emergent Adverse Events (TEAE) |
370; 202; 382; 362; 182; 381 | — |
| PRIMARY Number of Patients With Treatment-Emergent Adverse Events During AZD1775 Monotherapy Cycle by System Organ Class and Preferred Term |
1; 1; 2; 1; 1; 1 | — |
| PRIMARY Number of Patients With Clinically Important Changes in Haematology and Coagulation TEAEs by System Organ Class and Preferred Term |
6; 4; 5; 3; 0; 2 | — |
| PRIMARY Number of Patients With Clinically Important Abnormalities in Clinical Chemistry by Preferred Term |
0; 2; 1; 0; 1; 0 | — |
| PRIMARY Number of Patients With Clinically Important Abnormalities in Vital Signs by Preferred Term |
3; 1; 4; 2; 0; 1 | — |
| SECONDARY Best Overall Response |
1; 1; 3; 1; 2; 1 | — |
| SECONDARY Number of Patients With an Objective Response |
1; 1; 3 | — |
| SECONDARY Percentage of Patients With an Objective Response |
16.7; 16.7; 50 | — |
| SECONDARY Number of Patients With Clinical Benefit |
3; 3; 5 | — |
| SECONDARY Percentage of Patients With Clinical Benefit |
50; 50; 83.3 | — |
| SECONDARY Duration of Response |
18.1; 0.00; 20.7 | — |
| SECONDARY Peak Plasma Concentration (Cmax) of AZD1775 Following Single Dose Administration of AZD1775 Monotherapy |
689.1; 649.2; 1066 | — |
| SECONDARY Time to Maximum Plasma Concentration (Tmax) of AZD1775 Following Single Dose Administration of AZD1775 Monotherapy |
2.02; 3.95; 3.96 | — |
| 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 |
3521; 3387; 5331 | — |
| SECONDARY Plasma Concentration of AZD1775 8 Hours After Single Dose Administration (C8h) of AZD1775 Monotherapy |
370.1; 343.5; 612 | — |
| 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) |
705.4; 654.8; 1133 | — |
| 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) |
4.00; 4.04; 4.00 | — |
| 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) |
4191; 2902; 5606 | — |
| 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) |
444.6; 378.2; 805.9 | — |
| 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) |
1271; 1129; 2289 | — |
| 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) |
4.00; 3.09; 4.04 | — |
| 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) |
8300; 7154; 14870 | — |
| 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) |
982; 774.6; 1700 | — |
| SECONDARY Peak Plasma Concentration (Cmax) of Paclitaxel Following Single IV Infusion in Combination With Single Dose Oral AZD1775 and IV Carboplatin |
4848; 5361 | — |
| 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 |
13100; 16360 | — |
| SECONDARY Plasma Concentration of Paclitaxel at the End of Infusion (Ceoi) When Given Combination With Oral AZD1775 and IV Carboplatin. |
4791; 5361 | — |
| SECONDARY Time to Maximum Plasma Concentration (Tmax) of IV Paclitaxel When Given in Combination With Oral AZD1775 and IV Carboplatin |
2.99; 3.03 | — |
| SECONDARY Time to Last Detectable Concentration (Tlast) of Paclitaxel When Given in Combination With Oral AZD1775 and IV Carboplatin |
2.99; 3.03 | — |
| 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) |
13300; 18550; 17500 | — |
| 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) |
39370; 44630; 51340 | — |
| 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. |
13300; 18550; 17500 | — |
| SECONDARY Time to Peak Plasma Concentration of Platinum (Tmax) When Given as a 1 Hour Infusion in Combination With Oral AZD1775 and IV Paclitaxel. |
1.02; 1.02; 1.02 | — |
| SECONDARY Time to Last Detectable Concentration of Platinum (Tlast) When Given as a 1 Hour Infusion in Combination With Oral AZD1775 and IV Paclitaxel. |
7.98; 7.28; 8.00 | — |
| 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) |
15960; 13200 | — |
| 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) |
56240; 48700 | — |
| 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. |
15960; 12200 | — |
| SECONDARY Time to Peak Plasma Concentration of Platinum (Tmax) When Given as a 2 Hour Infusion in Combination With Oral AZD1775 and IV Paclitaxel. |
1.97; 1.08 | — |
| SECONDARY Time to Last Detectable Concentration of Platinum (Tlast) When Given as a 2 Hour Infusion in Combination With Oral AZD1775 and IV Paclitaxel. |
7.95; 8.00 | — |
Eligibility Criteria
Inclusion Criteria
- Histological or cytological confirmation of a locally advanced or metastatic solid tumour, excluding lymphoma, that failed to respond to standard therapy, progressed despite standard therapy, or for which standard therapy does not exist.
- At least 1 measureable lesion that can be accurately assessed at baseline by computerised tomography (CT) or magnetic resonance imaging (MRI) for solid tumours assessed using RECIST v1.1.
- World Health Organisation performance status 0 to 1 with no deterioration over the previous 2 weeks and a minimum life expectancy of ≥12 weeks.
Exclusion Criteria
- Any cytotoxic chemotherapy, investigational agents or other anticancer drugs from a previous treatment regimen or clinical study within 14 days (if investigational agent does not have well characterised PK profile) or 5 × half-lives of the first dose of study treatment
- Patient has had prescription or non-prescription drugs or other products (ie, grapefruit juice) known to be sensitive to CYP3A4 substrates or CYP3A4 substrates with a narrow therapeutic index, or to be moderate to strong inhibitors or inducers of CYP3A4, which cannot be discontinued 2 weeks before Day 1 of dosing and withheld throughout the study until 2 weeks after the last dose of study drug. Co-administration of aprepitant during this study is prohibited.
- AZD1775 is an inhibitor of breast cancer resistance protein (BCRP). The use of statins including Atorvastatin which are substrates for BCRP are therefore prohibited and patients should be moved on to non-BCRP alternatives.
Data sourced from ClinicalTrials.gov (NCT02341456). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.