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Phase Ib Study AZD1775 in Combination With Carboplatin and Paclitaxel in Adult Asian Patients With Solid Tumours

Sponsor
AstraZeneca (Industry)
Overall Status
Completed
CT.gov ID
NCT02341456
Collaborator
(none)
19
Enrollment
7
Locations
3
Arms
41.7
Actual Duration (Months)
2.7
Patients Per Site
0.1
Patients Per Site Per Month

Study Details

Study Description

Brief 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.

Condition or Disease Intervention/Treatment Phase
Phase 1

Detailed Description

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.

Study Design

Study Type:
Interventional
Actual Enrollment :
19 participants
Allocation:
Non-Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Phase Ib, Dose Finding Study Evaluating AZD1775 in Monotherapy, in Combination With Carboplatin and Paclitaxel, and in Combination With Only Carboplatin in Adult Asian Patients With Advanced Solid Tumours
Actual Study Start Date :
Jan 16, 2015
Actual Primary Completion Date :
Dec 14, 2016
Actual Study Completion Date :
Jul 9, 2018

Arms and Interventions

Arm Intervention/Treatment
Experimental: AZD1775

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.

Drug: AZD1775
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.
Other Names:
  • MK1775

    		•
    Experimental: Paclitaxel

    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.

    Drug: Paclitaxel
    Paclitaxel is a mitotic inhibitor used in cancer chemotherapy ; it and docetaxel represent the taxane family of drugs.
    Experimental: Carboplatin

    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.

    Drug: carboplatin
    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.).

    Outcome Measures

    Primary Outcome Measures

    1. Number of Patients With Treatment-Emergent Adverse Events [Up to 21 days (1 Cycle)]

      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.

    2. Number of Treatment-Emergent Adverse Events (TEAE) [Up to 21 days (1 Cycle)]

      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.

    3. Number of Patients With Treatment-Emergent Adverse Events During AZD1775 Monotherapy Cycle by System Organ Class and Preferred Term [Up to 1 week]

      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.

    4. Number of Patients With Clinically Important Changes in Haematology and Coagulation TEAEs by System Organ Class and Preferred Term [Up to 21 days (1 Cycle)]

      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.

    5. Number of Patients With Clinically Important Abnormalities in Clinical Chemistry by Preferred Term [Up to 21 days (1 Cycle)]

      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.

    6. Number of Patients With Clinically Important Abnormalities in Vital Signs by Preferred Term [Up to 21 days (1 Cycle)]

      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.

    Secondary Outcome Measures

    1. Best Overall Response [Up to 18 months]

      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.

    2. Number of Patients With an Objective Response [Up to 18 months]

      Objective response is defined as either a complete response or a partial response.

    3. Percentage of Patients With an Objective Response [Up to 18 months]

      Objective response is defined as either a complete response or a partial response.

    4. Number of Patients With Clinical Benefit [Up to 18 months]

      Clinical benefit is defined as achieving complete response, partial response, or stable disease.

    5. Percentage of Patients With Clinical Benefit [Up to 18 months]

      Clinical benefit is defined as achieving complete response, partial response, or stable disease.

    6. Duration of Response [Up to 18 months]

      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.

    7. 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]

    8. 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]

    9. 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]

    10. 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]

    11. 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]

    12. 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]

    13. 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]

    14. 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]

    15. 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]

    16. 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]

    17. 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]

    18. 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]

    19. 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]

    20. 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]

    21. 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]

    22. 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]

    23. 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]

    24. 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]

    25. 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]

    26. 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]

    27. 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]

    28. 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]

    29. 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]

    30. 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]

    31. 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]

    32. 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]

    33. 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]

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years to 100 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    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.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Research Site Liverpool Australia 2170
    2 Research Site Melbourne Australia 3004
    3 Research Site Kashiwa Japan 277-8577
    4 Research Site Sapporo-shi Japan 003-0804
    5 Research Site Seoul Korea, Republic of 03080
    6 Research Site Seoul Korea, Republic of 05505
    7 Research Site Seoul Korea, Republic of 135-710

    Sponsors and Collaborators

    • AstraZeneca

    Investigators

    • Principal Investigator: 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

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    AstraZeneca
    ClinicalTrials.gov Identifier:
    NCT02341456
    Other Study ID Numbers:
    • D6011C00003
    First Posted:
    Jan 19, 2015
    Last Update Posted:
    Mar 25, 2019
    Last Verified:
    Mar 1, 2019
    Additional relevant MeSH terms:
    Neoplasms
    Paclitaxel
    Carboplatin
    Adavosertib

    Study Results

    Participant Flow

    Recruitment Details 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.
    Pre-assignment Detail 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.
    Arm/Group Title Cohort 1 Cohort 1a Cohort 2
    Arm/Group Description 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. 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. 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.
    Period Title: Overall Study
    STARTED 7 6 6
    COMPLETED 3 0 2
    NOT COMPLETED 4 6 4

    Baseline Characteristics

    Arm/Group Title Cohort 1 Cohort 1a Cohort 2 Total
    Arm/Group Description 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. 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. 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. Total of all reporting groups
    Overall Participants 7 6 6 19
    Age (Count of Participants)
    <=18 years
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Between 18 and 65 years
    7
    100%
    6
    100%
    5
    83.3%
    18
    94.7%
    >=65 years
    0
    0%
    0
    0%
    1
    16.7%
    1
    5.3%
    Age (years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [years]
    55.0
    (5.23)
    43.0
    (14.10)
    52.2
    (13.82)
    50.3
    (12.04)
    Sex: Female, Male (Count of Participants)
    Female
    3
    42.9%
    3
    50%
    5
    83.3%
    11
    57.9%
    Male
    4
    57.1%
    3
    50%
    1
    16.7%
    8
    42.1%
    Ethnicity (NIH/OMB) (Count of Participants)
    Hispanic or Latino
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Not Hispanic or Latino
    7
    100%
    6
    100%
    6
    100%
    19
    100%
    Unknown or Not Reported
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Race/Ethnicity, Customized (Count of Participants)
    American Indian or Alaska Native
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Asian
    7
    100%
    6
    100%
    6
    100%
    19
    100%
    Native Hawaiian or Other Pacific Islander
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Black or African American
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    White
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    More than one race
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Unknown or Not Reported
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Region of Enrollment (Number) [Number]
    Australia
    2
    28.6%
    0
    0%
    0
    0%
    2
    10.5%
    Japan
    3
    42.9%
    1
    16.7%
    1
    16.7%
    7
    36.8%
    Korea, Republic Of
    2
    28.6%
    5
    83.3%
    5
    83.3%
    12
    63.2%
    Smoking History (Count of Participants)
    Never Used Tobacco
    4
    57.1%
    4
    66.7%
    3
    50%
    11
    57.9%
    Former Smoker
    3
    42.9%
    2
    33.3%
    2
    33.3%
    7
    36.8%
    Current Smoker
    0
    0%
    0
    0%
    1
    16.7%
    1
    5.3%
    Cancer Diagnosis (Count of Participants)
    Head and Neck
    2
    28.6%
    0
    0%
    0
    0%
    2
    10.5%
    Other; Gallbladder
    1
    14.3%
    0
    0%
    0
    0%
    1
    5.3%
    Stomach
    1
    14.3%
    0
    0%
    0
    0%
    1
    5.3%
    Cervix
    1
    14.3%
    1
    16.7%
    0
    0%
    2
    10.5%
    Ovary
    1
    14.3%
    0
    0%
    1
    16.7%
    2
    10.5%
    Uterus
    1
    14.3%
    0
    0%
    1
    16.7%
    2
    10.5%
    Breast
    0
    0%
    1
    16.7%
    3
    50%
    4
    21.1%
    Pancreas
    0
    0%
    1
    16.7%
    0
    0%
    1
    5.3%
    Other; Thymic
    0
    0%
    2
    33.3%
    0
    0%
    2
    10.5%
    Skin/Soft Tissue
    0
    0%
    1
    16.7%
    0
    0%
    1
    5.3%
    Lung
    0
    0%
    0
    0%
    1
    16.7%
    1
    5.3%
    Type of Tobacco Product Used (Count of Participants)
    Cigarettes
    3
    42.9%
    2
    33.3%
    3
    50%
    8
    42.1%
    Cigars
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Cigarillo
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    No history of tobacco use
    4
    57.1%
    4
    66.7%
    3
    50%
    11
    57.9%

    Outcome Measures

    1. Primary Outcome
    Title Number of Patients With Treatment-Emergent Adverse Events
    Description 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.
    Time Frame Up to 21 days (1 Cycle)

    Outcome Measure Data

    Analysis Population Description
    All patients who received at least one dose of the investigational drug.
    Arm/Group Title Cohort 1 Cohort 1a Cohort 2
    Arm/Group Description 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. 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. 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.
    Measure Participants 7 6 6
    Patients with ≥ 1 Adverse Event (AE)
    7
    100%
    6
    100%
    6
    100%
    Patients with ≥ 1 Treatment-Emergent AE (TEAE)
    6
    85.7%
    6
    100%
    6
    100%
    Patients with TEAE Related to Treatment
    6
    85.7%
    4
    66.7%
    6
    100%
    Patients with Serious TEAE
    3
    42.9%
    0
    0%
    4
    66.7%
    Patients with Severe TEAE
    6
    85.7%
    4
    66.7%
    6
    100%
    Patients with TEAE with AZD1775 discontinued
    1
    14.3%
    0
    0%
    2
    33.3%
    Patients with TEAE with paclitaxel discontinued
    1
    14.3%
    NA
    NaN
    2
    33.3%
    Patients with TEAE with carboplatin discontinued
    0
    0%
    0
    0%
    2
    33.3%
    Patients with TEAE and fatal outcome
    1
    14.3%
    0
    0%
    1
    16.7%
    Patients with Dose-Limiting Toxicity
    1
    14.3%
    1
    16.7%
    2
    33.3%
    2. Primary Outcome
    Title Number of Treatment-Emergent Adverse Events (TEAE)
    Description 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.
    Time Frame Up to 21 days (1 Cycle)

    Outcome Measure Data

    Analysis Population Description
    All patients who received at least one dose of the investigational drug.
    Arm/Group Title Cohort 1 Cohort 1a Cohort 2
    Arm/Group Description 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. 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. 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.
    Measure Participants 7 6 6
    Number of Adverse Events (AEs)
    370
    202
    382
    Number of TEAEs
    362
    182
    381
    Number of TEAEs Related to Study Treatment
    262
    95
    263
    Number of Serious TEAEs
    9
    0
    9
    Number of Severe TEAEs
    88
    23
    101
    Number of TEAEs with AZD1775 discontinued
    3
    0
    3
    Number of TEAEs with paclitaxel discontinued
    1
    NA
    3
    Number of TEAEs with carboplatin discontinued
    0
    0
    3
    Number of TEAEs with fatal outcome
    1
    0
    2
    Number of Dose-Limiting Toxicities (DLT)
    1
    1
    2
    Number of TEAEs with DLT
    1
    1
    2
    3. Primary Outcome
    Title Number of Patients With Treatment-Emergent Adverse Events During AZD1775 Monotherapy Cycle by System Organ Class and Preferred Term
    Description 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.
    Time Frame Up to 1 week

    Outcome Measure Data

    Analysis Population Description
    All patients who received at least one dose of the investigational drug.
    Arm/Group Title Cohort 1 Cohort 1a Cohort 2
    Arm/Group Description 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. 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. 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.
    Measure Participants 7 6 6
    Patients with at least 1 TEAE in AZD1775 cycle
    1
    14.3%
    1
    16.7%
    2
    33.3%
    Gastrointestinal Disorders - Nausea
    1
    14.3%
    1
    16.7%
    1
    16.7%
    Gastrointestinal Disorders - Constipation
    0
    0%
    0
    0%
    1
    16.7%
    Gastrointestinal Disorders - Diarrhoea
    0
    0%
    1
    16.7%
    0
    0%
    Immune System Disorders - Hypersensitivity
    0
    0%
    0
    0%
    1
    16.7%
    4. Primary Outcome
    Title Number of Patients With Clinically Important Changes in Haematology and Coagulation TEAEs by System Organ Class and Preferred Term
    Description 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.
    Time Frame Up to 21 days (1 Cycle)

    Outcome Measure Data

    Analysis Population Description
    All patients who received at least one dose of the investigational drug.
    Arm/Group Title Cohort 1 Cohort 1a Cohort 2
    Arm/Group Description 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. 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. 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.
    Measure Participants 7 6 6
    Blood & Lymphatic System Disorders (BLSD) Anaemia
    6
    85.7%
    4
    66.7%
    5
    83.3%
    BLSD - Neutropenia
    3
    42.9%
    0
    0%
    2
    33.3%
    BLSD - Thrombocytopenia
    1
    14.3%
    1
    16.7%
    2
    33.3%
    BLSD - Febrile Neutropenia
    1
    14.3%
    0
    0%
    2
    33.3%
    Investigations - WBC Count Decreased
    5
    71.4%
    3
    50%
    5
    83.3%
    Investigations - Neutrophil Count Decreased
    3
    42.9%
    4
    66.7%
    3
    50%
    Investigations - Platelet Count Decreased
    4
    57.1%
    3
    50%
    3
    50%
    Investigations - Haematocrit Decreased
    1
    14.3%
    0
    0%
    0
    0%
    Investigations - Monocyte Count Decreased
    1
    14.3%
    0
    0%
    0
    0%
    5. Primary Outcome
    Title Number of Patients With Clinically Important Abnormalities in Clinical Chemistry by Preferred Term
    Description 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.
    Time Frame Up to 21 days (1 Cycle)

    Outcome Measure Data

    Analysis Population Description
    All patients who received at least one dose of the investigational drug.
    Arm/Group Title Cohort 1 Cohort 1a Cohort 2
    Arm/Group Description 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. 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. 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.
    Measure Participants 7 6 6
    Aspartate aminotransferase increased
    0
    0%
    2
    33.3%
    1
    16.7%
    Alanine aminotransferase increased
    0
    0%
    1
    16.7%
    0
    0%
    Blood alkaline phosphatase increased
    1
    14.3%
    0
    0%
    0
    0%
    Blood lactate dehydrogenase increased
    1
    14.3%
    0
    0%
    0
    0%
    C-reactive protein increased
    1
    14.3%
    0
    0%
    0
    0%
    Hypoalbuminemia
    2
    28.6%
    0
    0%
    2
    33.3%
    Hypokalemia
    1
    14.3%
    1
    16.7%
    2
    33.3%
    Hypophosphatemia
    1
    14.3%
    0
    0%
    2
    33.3%
    Dehydration
    1
    14.3%
    0
    0%
    1
    16.7%
    Hyperglycaemia
    2
    28.6%
    0
    0%
    0
    0%
    Hypocalcaemia
    0
    0%
    0
    0%
    1
    16.7%
    Hyponatraemia
    1
    14.3%
    0
    0%
    1
    16.7%
    Hypercalcaemia
    0
    0%
    0
    0%
    1
    16.7%
    Hypercholsterolaemia
    0
    0%
    0
    0%
    1
    16.7%
    Hypoglycaemia
    1
    14.3%
    0
    0%
    0
    0%
    Hypomagnesaemia
    0
    0%
    0
    0%
    1
    16.7%
    Azotemia
    1
    14.3%
    0
    0%
    0
    0%
    Hepatic function abnormal
    1
    14.3%
    0
    0%
    0
    0%
    6. Primary Outcome
    Title Number of Patients With Clinically Important Abnormalities in Vital Signs by Preferred Term
    Description 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.
    Time Frame Up to 21 days (1 Cycle)

    Outcome Measure Data

    Analysis Population Description
    All patients who received at least one dose of the investigational drug.
    Arm/Group Title Cohort 1 Cohort 1a Cohort 2
    Arm/Group Description 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. 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. 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.
    Measure Participants 7 6 6
    Pyrexia
    3
    42.9%
    1
    16.7%
    4
    66.7%
    Hypotension
    2
    28.6%
    0
    0%
    1
    16.7%
    7. Secondary Outcome
    Title Best Overall Response
    Description 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.
    Time Frame Up to 18 months

    Outcome Measure Data

    Analysis Population Description
    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.
    Arm/Group Title Cohort 1 Cohort 1a Cohort 2
    Arm/Group Description 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. 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. 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.
    Measure Participants 6 6 6
    Partial Response
    1
    14.3%
    1
    16.7%
    3
    50%
    Not Evaluable
    1
    14.3%
    2
    33.3%
    1
    16.7%
    Stable Disease
    2
    28.6%
    2
    33.3%
    2
    33.3%
    Progressive Disease
    2
    28.6%
    1
    16.7%
    0
    0%
    Complete Response
    0
    0%
    0
    0%
    0
    0%
    8. Secondary Outcome
    Title Number of Patients With an Objective Response
    Description Objective response is defined as either a complete response or a partial response.
    Time Frame Up to 18 months

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Cohort 1 Cohort 1a Cohort 2
    Arm/Group Description 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. 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. 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.
    Measure Participants 6 6 6
    Number [Participants]
    1
    14.3%
    1
    16.7%
    3
    50%
    9. Secondary Outcome
    Title Percentage of Patients With an Objective Response
    Description Objective response is defined as either a complete response or a partial response.
    Time Frame Up to 18 months

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Cohort 1 Cohort 1a Cohort 2
    Arm/Group Description 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. 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. 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.
    Measure Participants 6 6 6
    Number (95% Confidence Interval) [Percentage]
    16.7
    16.7
    50
    10. Secondary Outcome
    Title Number of Patients With Clinical Benefit
    Description Clinical benefit is defined as achieving complete response, partial response, or stable disease.
    Time Frame Up to 18 months

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Cohort 1 Cohort 1a Cohort 2
    Arm/Group Description 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. 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. 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.
    Measure Participants 6 6 6
    Number [Participants]
    3
    42.9%
    3
    50%
    5
    83.3%
    11. Secondary Outcome
    Title Percentage of Patients With Clinical Benefit
    Description Clinical benefit is defined as achieving complete response, partial response, or stable disease.
    Time Frame Up to 18 months

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Cohort 1 Cohort 1a Cohort 2
    Arm/Group Description 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. 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. 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.
    Measure Participants 6 6 6
    Number (95% Confidence Interval) [Percentage]
    50
    50
    83.3
    12. Secondary Outcome
    Title Duration of Response
    Description 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.
    Time Frame Up to 18 months

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Cohort 1 Cohort 1a Cohort 2
    Arm/Group Description 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. 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. 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.
    Measure Participants 6 6 6
    Median (95% Confidence Interval) [Weeks]
    18.1
    0.00
    20.7
    13. Secondary Outcome
    Title Peak Plasma Concentration (Cmax) of AZD1775 Following Single Dose Administration of AZD1775 Monotherapy
    Description
    Time Frame 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

    Outcome Measure Data

    Analysis Population Description
    The pharmacokinetic analysis set consisted of all dosed patients for whom an adequate PK profile was obtained.
    Arm/Group Title Cohort 1 Cohort 1a Cohort 2
    Arm/Group Description 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. 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. 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.
    Measure Participants 6 4 6
    Geometric Mean (Geometric Coefficient of Variation) [nM]
    689.1
    (51.79)
    649.2
    (10.74)
    1066
    (38)
    14. Secondary Outcome
    Title Time to Maximum Plasma Concentration (Tmax) of AZD1775 Following Single Dose Administration of AZD1775 Monotherapy
    Description
    Time Frame 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

    Outcome Measure Data

    Analysis Population Description
    The pharmacokinetic analysis set consisted of all dosed patients for whom an adequate PK profile was obtained.
    Arm/Group Title Cohort 1 Cohort 1a Cohort 2
    Arm/Group Description 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. 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. 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.
    Measure Participants 7 5 6
    Median (Full Range) [hours]
    2.02
    3.95
    3.96
    15. Secondary Outcome
    Title 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
    Description
    Time Frame 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

    Outcome Measure Data

    Analysis Population Description
    The pharmacokinetic analysis set consisted of all dosed patients for whom an adequate PK profile was obtained.
    Arm/Group Title Cohort 1 Cohort 1a Cohort 2
    Arm/Group Description 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. 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. 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.
    Measure Participants 6 4 6
    Geometric Mean (Geometric Coefficient of Variation) [nM*h]
    3521
    (44.91)
    3387
    (12.54)
    5331
    (37.42)
    16. Secondary Outcome
    Title Plasma Concentration of AZD1775 8 Hours After Single Dose Administration (C8h) of AZD1775 Monotherapy
    Description
    Time Frame 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

    Outcome Measure Data

    Analysis Population Description
    The pharmacokinetic analysis set consisted of all dosed patients for whom an adequate PK profile was obtained.
    Arm/Group Title Cohort 1 Cohort 1a Cohort 2
    Arm/Group Description 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. 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. 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.
    Measure Participants 6 4 6
    Geometric Mean (Geometric Coefficient of Variation) [nM]
    370.1
    (29.15)
    343.5
    (29.97)
    612
    (36.6)
    17. Secondary Outcome
    Title 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)
    Description
    Time Frame 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

    Outcome Measure Data

    Analysis Population Description
    The pharmacokinetic analysis set consisted of all dosed patients for whom an adequate PK profile was obtained.
    Arm/Group Title Cohort 1 Cohort 1a Cohort 2
    Arm/Group Description 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. 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. 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.
    Measure Participants 5 5 6
    Geometric Mean (Geometric Coefficient of Variation) [nM]
    705.4
    (28.03)
    654.8
    (32.27)
    1133
    (16.3)
    18. Secondary Outcome
    Title 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)
    Description
    Time Frame 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

    Outcome Measure Data

    Analysis Population Description
    The pharmacokinetic analysis set consisted of all dosed patients for whom an adequate PK profile was obtained.
    Arm/Group Title Cohort 1 Cohort 1a Cohort 2
    Arm/Group Description 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. 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. 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.
    Measure Participants 6 6 6
    Median (Full Range) [hours]
    4.00
    4.04
    4.00
    19. Secondary Outcome
    Title 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)
    Description
    Time Frame 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

    Outcome Measure Data

    Analysis Population Description
    The pharmacokinetic analysis set consisted of all dosed patients for whom an adequate PK profile was obtained.
    Arm/Group Title Cohort 1 Cohort 1a Cohort 2
    Arm/Group Description 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. 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. 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.
    Measure Participants 5 5 6
    Geometric Mean (Geometric Coefficient of Variation) [nM*h]
    4191
    (34.89)
    2902
    (33.21)
    5606
    (20.02)
    20. Secondary Outcome
    Title 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)
    Description
    Time Frame 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

    Outcome Measure Data

    Analysis Population Description
    The pharmacokinetic analysis set consisted of all dosed patients for whom an adequate PK profile was obtained.
    Arm/Group Title Cohort 1 Cohort 1a Cohort 2
    Arm/Group Description 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. 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. 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.
    Measure Participants 6 6 6
    Geometric Mean (Geometric Coefficient of Variation) [nM]
    444.6
    (27.83)
    378.2
    (27.61)
    805.9
    (27.5)
    21. Secondary Outcome
    Title 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)
    Description
    Time Frame 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

    Outcome Measure Data

    Analysis Population Description
    The pharmacokinetic analysis set consisted of all dosed patients for whom an adequate PK profile was obtained.
    Arm/Group Title Cohort 1 Cohort 1a Cohort 2
    Arm/Group Description 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. 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. 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.
    Measure Participants 6 6 5
    Geometric Mean (Geometric Coefficient of Variation) [nM]
    1271
    (30.52)
    1129
    (25.51)
    2289
    (32.82)
    22. Secondary Outcome
    Title 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)
    Description
    Time Frame 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

    Outcome Measure Data

    Analysis Population Description
    The pharmacokinetic analysis set consisted of all dosed patients for whom an adequate PK profile was obtained.
    Arm/Group Title Cohort 1 Cohort 1a Cohort 2
    Arm/Group Description 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. 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. 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.
    Measure Participants 6 6 6
    Median (Full Range) [hours]
    4.00
    3.09
    4.04
    23. Secondary Outcome
    Title 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)
    Description
    Time Frame 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

    Outcome Measure Data

    Analysis Population Description
    The pharmacokinetic analysis set consisted of all dosed patients for whom an adequate PK profile was obtained.
    Arm/Group Title Cohort 1 Cohort 1a Cohort 2
    Arm/Group Description 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. 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. 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.
    Measure Participants 6 6 5
    Geometric Mean (Geometric Coefficient of Variation) [nM*h]
    8300
    (32.85)
    7154
    (32.29)
    14870
    (34.05)
    24. Secondary Outcome
    Title 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)
    Description
    Time Frame 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

    Outcome Measure Data

    Analysis Population Description
    The pharmacokinetic analysis set consisted of all dosed patients for whom an adequate PK profile was obtained.
    Arm/Group Title Cohort 1 Cohort 1a Cohort 2
    Arm/Group Description 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. 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. 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.
    Measure Participants 6 6 6
    Geometric Mean (Geometric Coefficient of Variation) [nM]
    982
    (30.17)
    774.6
    (32.96)
    1700
    (37.6)
    25. Secondary Outcome
    Title Peak Plasma Concentration (Cmax) of Paclitaxel Following Single IV Infusion in Combination With Single Dose Oral AZD1775 and IV Carboplatin
    Description
    Time Frame 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

    Outcome Measure Data

    Analysis Population Description
    The pharmacokinetic analysis set consisted of all dosed patients for whom an adequate PK profile was obtained.
    Arm/Group Title Cohort 1 Cohort 1a Cohort 2
    Arm/Group Description 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. 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. 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.
    Measure Participants 6 0 4
    Geometric Mean (Geometric Coefficient of Variation) [ng/mL]
    4848
    (31.13)
    5361
    (4.744)
    26. Secondary Outcome
    Title 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
    Description
    Time Frame 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

    Outcome Measure Data

    Analysis Population Description
    The pharmacokinetic analysis set consisted of all dosed patients for whom an adequate PK profile was obtained.
    Arm/Group Title Cohort 1 Cohort 1a Cohort 2
    Arm/Group Description 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. 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. 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.
    Measure Participants 6 0 4
    Geometric Mean (Geometric Coefficient of Variation) [h*ng/mL]
    13100
    (36.11)
    16360
    (20.11)
    27. Secondary Outcome
    Title Plasma Concentration of Paclitaxel at the End of Infusion (Ceoi) When Given Combination With Oral AZD1775 and IV Carboplatin.
    Description
    Time Frame 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

    Outcome Measure Data

    Analysis Population Description
    The pharmacokinetic analysis set consisted of all dosed patients for whom an adequate PK profile was obtained.
    Arm/Group Title Cohort 1 Cohort 1a Cohort 2
    Arm/Group Description 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. 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. 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.
    Measure Participants 6 0 4
    Geometric Mean (Geometric Coefficient of Variation) [ng/mL]
    4791
    (32.33)
    5361
    (4.744)
    28. Secondary Outcome
    Title Time to Maximum Plasma Concentration (Tmax) of IV Paclitaxel When Given in Combination With Oral AZD1775 and IV Carboplatin
    Description
    Time Frame 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

    Outcome Measure Data

    Analysis Population Description
    The pharmacokinetic analysis set consisted of all dosed patients for whom an adequate PK profile was obtained.
    Arm/Group Title Cohort 1 Cohort 1a Cohort 2
    Arm/Group Description 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. 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. 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.
    Measure Participants 6 0 4
    Median (Full Range) [hours]
    2.99
    3.03
    29. Secondary Outcome
    Title Time to Last Detectable Concentration (Tlast) of Paclitaxel When Given in Combination With Oral AZD1775 and IV Carboplatin
    Description
    Time Frame 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

    Outcome Measure Data

    Analysis Population Description
    The pharmacokinetic analysis set consisted of all dosed patients for whom an adequate PK profile was obtained.
    Arm/Group Title Cohort 1 Cohort 1a Cohort 2
    Arm/Group Description 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. 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. 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.
    Measure Participants 6 0 4
    Median (Full Range) [hours]
    2.99
    3.03
    30. Secondary Outcome
    Title 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)
    Description
    Time Frame 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

    Outcome Measure Data

    Analysis Population Description
    The pharmacokinetic analysis set consisted of all dosed patients for whom an adequate PK profile was obtained.
    Arm/Group Title Cohort 1 Cohort 1a Cohort 2
    Arm/Group Description 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. 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. 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.
    Measure Participants 3 4 3
    Geometric Mean (Geometric Coefficient of Variation) [ng/mL]
    13300
    (17.41)
    18550
    (19.87)
    17500
    (34.93)
    31. Secondary Outcome
    Title 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)
    Description
    Time Frame 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

    Outcome Measure Data

    Analysis Population Description
    The pharmacokinetic analysis set consisted of all dosed patients for whom an adequate PK profile was obtained.
    Arm/Group Title Cohort 1 Cohort 1a Cohort 2
    Arm/Group Description 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. 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. 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.
    Measure Participants 3 4 3
    Geometric Mean (Geometric Coefficient of Variation) [h*ng/mL]
    39370
    (7.027)
    44630
    (2.552)
    51340
    (12.24)
    32. Secondary Outcome
    Title 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.
    Description
    Time Frame 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

    Outcome Measure Data

    Analysis Population Description
    The pharmacokinetic analysis set consisted of all dosed patients for whom an adequate PK profile was obtained.
    Arm/Group Title Cohort 1 Cohort 1a Cohort 2
    Arm/Group Description 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. 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. 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.
    Measure Participants 3 4 3
    Geometric Mean (Geometric Coefficient of Variation) [ng/mL]
    13300
    (17.41)
    18550
    (19.87)
    17500
    (34.93)
    33. Secondary Outcome
    Title Time to Peak Plasma Concentration of Platinum (Tmax) When Given as a 1 Hour Infusion in Combination With Oral AZD1775 and IV Paclitaxel.
    Description
    Time Frame 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

    Outcome Measure Data

    Analysis Population Description
    The pharmacokinetic analysis set consisted of all dosed patients for whom an adequate PK profile was obtained.
    Arm/Group Title Cohort 1 Cohort 1a Cohort 2
    Arm/Group Description 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. 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. 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.
    Measure Participants 3 4 3
    Median (Full Range) [hours]
    1.02
    1.02
    1.02
    34. Secondary Outcome
    Title Time to Last Detectable Concentration of Platinum (Tlast) When Given as a 1 Hour Infusion in Combination With Oral AZD1775 and IV Paclitaxel.
    Description
    Time Frame 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

    Outcome Measure Data

    Analysis Population Description
    The pharmacokinetic analysis set consisted of all dosed patients for whom an adequate PK profile was obtained.
    Arm/Group Title Cohort 1 Cohort 1a Cohort 2
    Arm/Group Description 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. 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. 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.
    Measure Participants 3 4 3
    Median (Full Range) [hours]
    7.98
    7.28
    8.00
    35. Secondary Outcome
    Title 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)
    Description
    Time Frame 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

    Outcome Measure Data

    Analysis Population Description
    The pharmacokinetic analysis set consisted of all dosed patients for whom an adequate PK profile was obtained.
    Arm/Group Title Cohort 1 Cohort 1a Cohort 2
    Arm/Group Description 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. 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. 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.
    Measure Participants 3 1 0
    Geometric Mean (Geometric Coefficient of Variation) [ng/mL]
    15960
    (26.51)
    13200
    (0)
    36. Secondary Outcome
    Title 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)
    Description
    Time Frame 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

    Outcome Measure Data

    Analysis Population Description
    The pharmacokinetic analysis set consisted of all dosed patients for whom an adequate PK profile was obtained.
    Arm/Group Title Cohort 1 Cohort 1a Cohort 2
    Arm/Group Description 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. 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. 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.
    Measure Participants 6 1 0
    Geometric Mean (Geometric Coefficient of Variation) [h*ng/mL]
    56240
    (17.2)
    48700
    (0)
    37. Secondary Outcome
    Title 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.
    Description
    Time Frame 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

    Outcome Measure Data

    Analysis Population Description
    The pharmacokinetic analysis set consisted of all dosed patients for whom an adequate PK profile was obtained.
    Arm/Group Title Cohort 1 Cohort 1a Cohort 2
    Arm/Group Description 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. 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. 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.
    Measure Participants 3 1 0
    Geometric Mean (Geometric Coefficient of Variation) [ng/mL]
    15960
    (26.51)
    12200
    (0)
    38. Secondary Outcome
    Title Time to Peak Plasma Concentration of Platinum (Tmax) When Given as a 2 Hour Infusion in Combination With Oral AZD1775 and IV Paclitaxel.
    Description
    Time Frame 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

    Outcome Measure Data

    Analysis Population Description
    The pharmacokinetic analysis set consisted of all dosed patients for whom an adequate PK profile was obtained.
    Arm/Group Title Cohort 1 Cohort 1a Cohort 2
    Arm/Group Description 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. 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. 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.
    Measure Participants 3 1 0
    Median (Full Range) [hours]
    1.97
    1.08
    39. Secondary Outcome
    Title Time to Last Detectable Concentration of Platinum (Tlast) When Given as a 2 Hour Infusion in Combination With Oral AZD1775 and IV Paclitaxel.
    Description
    Time Frame 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

    Outcome Measure Data

    Analysis Population Description
    The pharmacokinetic analysis set consisted of all dosed patients for whom an adequate PK profile was obtained.
    Arm/Group Title Cohort 1 Cohort 1a Cohort 2
    Arm/Group Description 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. 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. 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.
    Measure Participants 3 1 0
    Median (Full Range) [hours]
    7.95
    8.00

    Adverse Events

    Time Frame Up to 18 months.
    Adverse Event Reporting Description
    Arm/Group Title Cohort 1 Cohort 1a Cohort 2
    Arm/Group Description 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. 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. 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.
    All Cause Mortality
    Cohort 1 Cohort 1a Cohort 2
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 1/7 (14.3%) 1/6 (16.7%) 1/6 (16.7%)
    Serious Adverse Events
    Cohort 1 Cohort 1a Cohort 2
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 3/7 (42.9%) 0/6 (0%) 4/6 (66.7%)
    Blood and lymphatic system disorders
    Febrile neutropenia 1/7 (14.3%) 1 0/6 (0%) 0 1/6 (16.7%) 1
    Neutropenia 0/7 (0%) 0 0/6 (0%) 0 2/6 (33.3%) 3
    Gastrointestinal disorders
    Diarrhoea 0/7 (0%) 0 0/6 (0%) 0 1/6 (16.7%) 1
    Nausea 1/7 (14.3%) 1 0/6 (0%) 0 0/6 (0%) 0
    Vomiting 1/7 (14.3%) 1 0/6 (0%) 0 0/6 (0%) 0
    General disorders
    Pyrexia 1/7 (14.3%) 1 0/6 (0%) 0 0/6 (0%) 0
    Hepatobiliary disorders
    Hepatic function abnormal 1/7 (14.3%) 1 0/6 (0%) 0 0/6 (0%) 0
    Infections and infestations
    Sepsis 0/7 (0%) 0 0/6 (0%) 0 2/6 (33.3%) 2
    Clostridium difficile colitis 0/7 (0%) 0 0/6 (0%) 0 1/6 (16.7%) 1
    Investigations
    Platelet count decreased 1/7 (14.3%) 2 0/6 (0%) 0 0/6 (0%) 0
    Respiratory, thoracic and mediastinal disorders
    Acute respiratory distress syndrome 0/7 (0%) 0 0/6 (0%) 0 1/6 (16.7%) 1
    Vascular disorders
    Hypotension 1/7 (14.3%) 1 0/6 (0%) 0 0/6 (0%) 0
    Other (Not Including Serious) Adverse Events
    Cohort 1 Cohort 1a Cohort 2
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 7/7 (100%) 6/6 (100%) 6/6 (100%)
    Blood and lymphatic system disorders
    Anaemia 6/7 (85.7%) 48 4/6 (66.7%) 21 5/6 (83.3%) 37
    Neutropenia 3/7 (42.9%) 18 0/6 (0%) 0 2/6 (33.3%) 9
    Thrombocytopenia 1/7 (14.3%) 9 1/6 (16.7%) 6 2/6 (33.3%) 23
    Febrile Neutropenia 0/7 (0%) 0 0/6 (0%) 0 2/6 (33.3%) 2
    Eye disorders
    Eyelid Oedema 0/7 (0%) 0 0/6 (0%) 0 1/6 (16.7%) 1
    Gastrointestinal disorders
    Nausea 6/7 (85.7%) 36 6/6 (100%) 27 5/6 (83.3%) 37
    Abdominal pain upper 1/7 (14.3%) 1 1/6 (16.7%) 2 0/6 (0%) 0
    Constipation 2/7 (28.6%) 4 0/6 (0%) 0 3/6 (50%) 5
    Diarrhoea 5/7 (71.4%) 25 3/6 (50%) 13 4/6 (66.7%) 49
    Abdominal distension 1/7 (14.3%) 1 1/6 (16.7%) 1 1/6 (16.7%) 1
    Abdominal pain 2/7 (28.6%) 4 2/6 (33.3%) 4 2/6 (33.3%) 7
    Dyspepsia 1/7 (14.3%) 1 0/6 (0%) 0 0/6 (0%) 0
    Vomiting 5/7 (71.4%) 20 4/6 (66.7%) 15 5/6 (83.3%) 27
    Oesphageal disorder 1/7 (14.3%) 1 0/6 (0%) 0 0/6 (0%) 0
    Ileus 1/7 (14.3%) 1 0/6 (0%) 0 0/6 (0%) 0
    Dysphagia 1/7 (14.3%) 1 0/6 (0%) 0 0/6 (0%) 0
    Proctologia 1/7 (14.3%) 1 1/6 (16.7%) 1 3/6 (50%) 7
    Intestinal obstruction 0/7 (0%) 0 1/6 (16.7%) 1 0/6 (0%) 0
    Gingival pain 0/7 (0%) 0 1/6 (16.7%) 1 0/6 (0%) 0
    Anal Haemorrhage 0/7 (0%) 0 0/6 (0%) 0 1/6 (16.7%) 1
    General disorders
    Oedema 2/7 (28.6%) 2 1/6 (16.7%) 1 0/6 (0%) 0
    Fatugue 2/7 (28.6%) 3 2/6 (33.3%) 5 1/6 (16.7%) 1
    Gait disturbance 1/7 (14.3%) 1 0/6 (0%) 0 0/6 (0%) 0
    Pyrexia 3/7 (42.9%) 11 2/6 (33.3%) 4 4/6 (66.7%) 9
    Asthenia 1/7 (14.3%) 2 1/6 (16.7%) 1 2/6 (33.3%) 4
    Chills 1/7 (14.3%) 1 1/6 (16.7%) 1 0/6 (0%) 0
    Chest pain 0/7 (0%) 0 1/6 (16.7%) 1 0/6 (0%) 0
    Malaise 0/7 (0%) 0 1/6 (16.7%) 7 0/6 (0%) 0
    Immune system disorders
    Hypersensitivity 0/7 (0%) 0 0/6 (0%) 0 1/6 (16.7%) 1
    Infections and infestations
    Herpes zoster 1/7 (14.3%) 1 0/6 (0%) 0 0/6 (0%) 0
    Liver abscess 1/7 (14.3%) 1 0/6 (0%) 0 0/6 (0%) 0
    Cystitis 1/7 (14.3%) 2 0/6 (0%) 0 0/6 (0%) 0
    Bone abscess 0/7 (0%) 0 0/6 (0%) 0 1/6 (16.7%) 2
    Urinary tract infection 0/7 (0%) 0 0/6 (0%) 0 1/6 (16.7%) 1
    Anal infection 0/7 (0%) 0 0/6 (0%) 0 1/6 (16.7%) 1
    Herpes simplex 0/7 (0%) 0 0/6 (0%) 0 1/6 (16.7%) 1
    Fallopian tube abscess 0/7 (0%) 0 0/6 (0%) 0 1/6 (16.7%) 1
    Injury, poisoning and procedural complications
    Postoperative wound complication 1/7 (14.3%) 1 0/6 (0%) 0 0/6 (0%) 0
    Radiation skin injury 1/7 (14.3%) 1 0/6 (0%) 0 0/6 (0%) 0
    Rash 1/7 (14.3%) 1 0/6 (0%) 0 0/6 (0%) 0
    Postoperative pain 0/7 (0%) 0 0/6 (0%) 0 1/6 (16.7%) 2
    Investigations
    Blood lactate dehydrogenase increased 1/7 (14.3%) 2 0/6 (0%) 0 0/6 (0%) 0
    C-reactive protein increased 1/7 (14.3%) 3 0/6 (0%) 0 0/6 (0%) 0
    Hematocrit decreased 1/7 (14.3%) 3 0/6 (0%) 0 0/6 (0%) 0
    Monocyte count decreased 1/7 (14.3%) 1 0/6 (0%) 0 0/6 (0%) 0
    Platelet count decreased 4/7 (57.1%) 50 3/6 (50%) 29 3/6 (50%) 21
    White blood cell count decreased 5/7 (71.4%) 26 3/6 (50%) 10 5/6 (83.3%) 31
    Blood alklaine phosphatase increased 1/7 (14.3%) 1 0/6 (0%) 0 0/6 (0%) 0
    Neutrophil count decreased 3/7 (42.9%) 10 4/6 (66.7%) 8 3/6 (50%) 15
    Aspartate aminotransferase increased 0/7 (0%) 0 2/6 (33.3%) 6 1/6 (16.7%) 1
    Alanine aminotransferase increased 0/7 (0%) 0 1/6 (16.7%) 4 0/6 (0%) 0
    Metabolism and nutrition disorders
    Decreased appetite 4/7 (57.1%) 5 4/6 (66.7%) 10 3/6 (50%) 4
    Hyperglycaemia 3/7 (42.9%) 12 0/6 (0%) 0 0/6 (0%) 0
    Hypoalbuminemia 2/7 (28.6%) 2 0/6 (0%) 0 2/6 (33.3%) 5
    Hypomagnesaemia 1/7 (14.3%) 1 0/6 (0%) 0 1/6 (16.7%) 2
    Dehydration 1/7 (14.3%) 1 0/6 (0%) 0 1/6 (16.7%) 1
    Hypocalcaemia 1/7 (14.3%) 4 1/6 (16.7%) 1 1/6 (16.7%) 4
    Hypokalemia 1/7 (14.3%) 1 2/6 (33.3%) 2 2/6 (33.3%) 5
    Hyponatremia 1/7 (14.3%) 2 0/6 (0%) 0 1/6 (16.7%) 1
    Hypophosphatemia 1/7 (14.3%) 3 1/6 (16.7%) 1 2/6 (33.3%) 6
    Hypercalcemia 0/7 (0%) 0 0/6 (0%) 0 1/6 (16.7%) 6
    Hypercholesterolemia 0/7 (0%) 0 0/6 (0%) 0 1/6 (16.7%) 1
    Musculoskeletal and connective tissue disorders
    Back pain 2/7 (28.6%) 2 1/6 (16.7%) 1 0/6 (0%) 0
    Myalgia 2/7 (28.6%) 2 0/6 (0%) 0 2/6 (33.3%) 3
    Pain in extremity 1/7 (14.3%) 1 0/6 (0%) 0 0/6 (0%) 0
    Arthralgia 2/7 (28.6%) 2 0/6 (0%) 0 0/6 (0%) 0
    Muscle spasms 1/7 (14.3%) 1 0/6 (0%) 0 0/6 (0%) 0
    Flank pain 0/7 (0%) 0 1/6 (16.7%) 1 0/6 (0%) 0
    Musculoskeletal pain 0/7 (0%) 0 0/6 (0%) 0 1/6 (16.7%) 3
    Low back pain 0/7 (0%) 0 0/6 (0%) 0 1/6 (16.7%) 1
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Tumour pain 1/7 (14.3%) 1 0/6 (0%) 0 0/6 (0%) 0
    Nervous system disorders
    Lethargy 1/7 (14.3%) 1 0/6 (0%) 0 0/6 (0%) 0
    Neuralgia 1/7 (14.3%) 1 0/6 (0%) 0 0/6 (0%) 0
    Peripheral sensory neuropathy 2/7 (28.6%) 4 2/6 (33.3%) 2 1/6 (16.7%) 2
    Peripheral neuropathy 1/7 (14.3%) 3 0/6 (0%) 0 1/6 (16.7%) 1
    Headache 1/7 (14.3%) 1 1/6 (16.7%) 1 2/6 (33.3%) 2
    Dizziness 0/7 (0%) 0 1/6 (16.7%) 1 1/6 (16.7%) 1
    Akathisia 0/7 (0%) 0 0/6 (0%) 0 1/6 (16.7%) 1
    Psychiatric disorders
    Anxiety 1/7 (14.3%) 2 1/6 (16.7%) 2 0/6 (0%) 0
    Insomnia 1/7 (14.3%) 2 2/6 (33.3%) 2 2/6 (33.3%) 5
    Renal and urinary disorders
    Azotemia 1/7 (14.3%) 1 0/6 (0%) 0 0/6 (0%) 0
    Micturition urgency 1/7 (14.3%) 2 0/6 (0%) 0 0/6 (0%) 0
    Chromaturia 0/7 (0%) 0 0/6 (0%) 0 1/6 (16.7%) 1
    Reproductive system and breast disorders
    Vaginal haemorrhage 0/7 (0%) 0 0/6 (0%) 0 1/6 (16.7%) 1
    Respiratory, thoracic and mediastinal disorders
    Pleural effusion 2/7 (28.6%) 3 1/6 (16.7%) 1 2/6 (33.3%) 3
    Oropharyngeal discomfort 1/7 (14.3%) 1 0/6 (0%) 0 1/6 (16.7%) 1
    Productive cough 0/7 (0%) 0 2/6 (33.3%) 2 0/6 (0%) 0
    Dyspnoea 0/7 (0%) 0 2/6 (33.3%) 2 1/6 (16.7%) 2
    Sputum increased 0/7 (0%) 0 0/6 (0%) 0 1/6 (16.7%) 1
    Pneumothorax 0/7 (0%) 0 0/6 (0%) 0 1/6 (16.7%) 1
    Skin and subcutaneous tissue disorders
    Alopecia 2/7 (28.6%) 3 0/6 (0%) 0 1/6 (16.7%) 1
    Pruritus 1/7 (14.3%) 1 0/6 (0%) 0 1/6 (16.7%) 1
    Ingrown nail 1/7 (14.3%) 1 0/6 (0%) 0 1/6 (16.7%) 1
    Vascular skin disorder 1/7 (14.3%) 1 0/6 (0%) 0 0/6 (0%) 0
    Dry skin 1/7 (14.3%) 1 0/6 (0%) 0 0/6 (0%) 0
    Pruritus generalised 0/7 (0%) 0 1/6 (16.7%) 1 0/6 (0%) 0
    Hyperhydrosis 0/7 (0%) 0 1/6 (16.7%) 1 0/6 (0%) 0
    Surgical and medical procedures
    Oophorectomy 0/7 (0%) 0 0/6 (0%) 0 1/6 (16.7%) 1
    Vascular disorders
    Hypotension 2/7 (28.6%) 2 0/6 (0%) 0 1/6 (16.7%) 3
    Arteriosclerosis 1/7 (14.3%) 1 0/6 (0%) 0 0/6 (0%) 0

    Limitations/Caveats

    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.

    More Information

    Certain Agreements

    Principal Investigators are NOT employed by the organization sponsoring the study.

    There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

    Results Point of Contact

    Name/Title Lone Ottesen
    Organization AstraZeneca
    Phone 1-877-240-9479
    Email ClinicalTrialTransparency@astrazeneca.com
    Responsible Party:
    AstraZeneca
    ClinicalTrials.gov Identifier:
    NCT02341456
    Other Study ID Numbers:
    • D6011C00003
    First Posted:
    Jan 19, 2015
    Last Update Posted:
    Mar 25, 2019
    Last Verified:
    Mar 1, 2019