Clincosm LogoSign in Get a demo

Ph II Trial of Carboplatin and Pemetrexed With or Without AZD1775 for Untreated Lung Cancer

Sponsor
AstraZeneca (Industry)
Overall Status
Terminated
CT.gov ID
NCT02087241
Collaborator
(none)
22
Enrollment
8
Locations
2
Arms
15
Duration (Months)
2.8
Patients Per Site
0.2
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The aim of this study is to combine AZD1775 with standard front-line chemotherapy in subjects with advanced NSCLC.

Condition or Disease Intervention/Treatment Phase
Phase 2

Detailed Description

This is a randomised, phase II trial comparing AZD1775 plus pemetrexed and carboplatin followed by maintenance AZD1775 and pemetrexed versus pemetrexed and carboplatin followed by maintenance pemetrexed in patients with previously untreated metastatic non-squamous NSCLC with TP53 mutations. The primary endpoint of the trial is assessment of progression-free survival (PFS).

Study Design

Study Type:
Interventional
Actual Enrollment :
22 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:
Treatment
Official Title:
A Phase II Study of AZD1775 Plus Pemetrexed and Carboplatin Followed by a Randomised Comparison of Pemetrexed and Carboplatin With or Without AZD1775 in Patients With Previously Untreated Stage IV Non-Squamous Non-Small-Cell Lung Cancer
Study Start Date :
Mar 1, 2014
Actual Primary Completion Date :
Jun 1, 2015
Actual Study Completion Date :
Jun 1, 2015

Arms and Interventions

Arm Intervention/Treatment
Experimental: AZD1775 + carboplatin + pemetrexed

Randomised: AZD1775 + pemetrexed + carboplatin followed by maintenance AZD1775 + pemetrexed versus pemetrexed and carboplatin followed by maintenance pemetrexed.

Drug: AZD1775
AZD1775 is a highly selective, adenosine-triphosphate (ATP) competitive, small molecule inhibitor of the WEE 1 kinase that sensitizes tumor cells to cytotoxic agents and is being developed for the treatment of advanced solid tumors and p53 pathway deficient malignancies
Other Names:
  • MK-1775

    • Drug: pemetrexed
    This drug is a part of a general group of chemotherapy drugs called anti-metabolites. It prevents cells from using folate to make DNA and RNA. Because cancer cells need these substances to make new cells, this drug helps to stop the growth of cancer cells.

    Drug: carboplatin
    This drug is a platinum chemotherapy drug that acts like an alkylating agent. It stops the growth of cancer cells, causing the cells to die.
    Experimental: Placebo + carboplatin + pemetrexed

    Randomised: AZD1775 + pemetrexed + carboplatin followed by maintenance AZD1775 + pemetrexed versus pemetrexed and carboplatin followed by maintenance pemetrexed.

    Drug: AZD1775 Matching Placebo
    AZD1775 is a highly selective, adenosine-triphosphate (ATP) competitive, small molecule inhibitor of the WEE 1 kinase that sensitizes tumor cells to cytotoxic agents and is being developed for the treatment of advanced solid tumors and p53 pathway deficient malignancies

    Drug: pemetrexed
    This drug is a part of a general group of chemotherapy drugs called anti-metabolites. It prevents cells from using folate to make DNA and RNA. Because cancer cells need these substances to make new cells, this drug helps to stop the growth of cancer cells.

    Drug: carboplatin
    This drug is a platinum chemotherapy drug that acts like an alkylating agent. It stops the growth of cancer cells, causing the cells to die.

    Outcome Measures

    Primary Outcome Measures

    1. Progression Free Survival [6 months]

      Progression free survival is defined as the time from randomisation until the date of objective disease progression or death (by any cause in the absence of progression) regardless of whether the subject withdraws from randomised therapy or receives another anti-cancer therapy prior to progression.

    Secondary Outcome Measures

    1. Assess the Objective Response Rates in Each Arm [Up to a maximum of 4 treatment cycles (treatment cycles will be repeated every 21 days)]

      The objective response rate is defined as the number of the subjects with a confirmed best overall response of CR or PR divided by the number of subjects in the Full Analysis Set (FAS) for whom measureable disease is present at baseline

    2. Assess the Disease Control Rate in Each Treatment Arm [Up to a maximum of 4 treatment cycles (treatment cycles will be repeated every 21 days)]

      the disease control rate is defined as the percentage of FAS subjects with a best overall response of CR, PR or SD).

    3. Assess the Duration of Response in Each Treatment Arm [Up to a maximum of 4 treatment cycles (treatment cycles will be repeated every 21 days)]

      Duration of response is defined as the time from the date of first documented response until the date of documented progression or any cause death.

    4. Assess Overall Survival in Each Treatment Arm [Up to a maximum of 4 treatment cycles (treatment cycles will be repeated every 21 days)]

      Overall survival is defined as the time from the date of randomization until death due to any cause.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No

    Inclusion Criteria

    • Provision of informed consent prior to any study specific procedures

    • Histologic or cytologic diagnosis of advanced NSCLC, Recurrent or Stage IV disease (according to American Joint Committee on Cancer (AJCC) staging system, v7.0).

    • No prior chemotherapy for locally advanced or metastatic disease

    • Subjects with a known EGFR mutation must have received previous treatment with an EGFR tyrosine kinase inhibitor; and subjects with a known ALK translocation must have received previous treatment with an ALK inhibitor.

    • No prior radiation therapy to the whole pelvis or to ≥25% of the total bone marrow area.

    • At least one measurable lesion according to Response Evaluation Criteria in Solid Tumours (RECIST) v1.1

    • Mandatory availability of tumour tissue (archival or fresh if archival is not available) for TP53 determination.

    • Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) score of 0 or 1.

    • Absolute neutrophil count (ANC) ≥1500/μL

    • Hemoglobin (Hgb) ≥10 g/dL

    • Platelets ≥100,000/μL

    • Alanine aminotransferase (ALT) and aspartate aminotransferase (AST), ≤3.0 x the upper limit of normal (ULN); 5 x ULN if known hepatic metastases

    • Total bilirubin ≤1.5 x ULN, unless secondary to Gilbert's disease

    • Serum creatinine ≤1.5 x ULN and a calculate creatinine clearance (CrCl) ≥45 mL/min by the Cockcroft-Gault method

    • Ability to swallow oral medication

    • Fertile male subjects willing to use at least one medically acceptable form of birth control for the duration of the study and for 2 weeks after treatment stops

    • Female subjects who are not of childbearing potential and fertile female subjects of childbearing potential who agree to use adequate contraceptive measures who are not breastfeeding, and who have a negative serum or urine pregnancy test within 72 hours prior to start of study treatment

    • Predicted life expectancy ≥12 weeks

    • Must be ≥18 years of age

    • Willingness and ability to comply with study and follow-up procedures

    • Ability to understand the nature of this trial and give written informed consent Exclusion criteria

    • Use of a study drug ≤21 days or 5 half-lives (whichever is shorter) prior to the first dose of AZD1775

    • Major surgical procedures ≤28 days of beginning AZD1775, or minor surgical procedures ≤7 days

    • Known central nervous system (CNS) disease

    • Subject has had prescription or non-prescription drugs or other products (i.e. grapefruit juice) known to be sensitive CYP3A4 substrates

    • Any known hypersensitivity or contraindication to the components of study treatment

    • Any of the following cardiac diseases currently or within the last 6 months as defined by New York Heart Association ([NYHA] Appendix G) ≥ Class 2

    • Corrected QT interval (QTc) >470 msec (as calculated by Fridericia correction formula) at study entry or congenital long QT syndrome.

    • Pregnant or lactating

    • Any serious, active underlying medical condition that would impair the ability of the subjects to receive study treatment

    • Unable or unwilling to take folic acid or vitamin B12

    • Presence of other active cancers, or history of treatment for invasive cancer ≤3 years

    • Psychological, familial, sociological, or geographical conditions that do not permit compliance with the protocol

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Research Site Englewood Colorado United States
    2 Research Site Fort Myers Florida United States
    3 Research Site Orlando Florida United States
    4 Research Site Peoria Illinois United States
    5 Research Site Fort Wayne Indiana United States
    6 Research Site Wichita Kansas United States
    7 Research Site Cincinnati Ohio United States
    8 Research Site Nashville Tennessee United States

    Sponsors and Collaborators

    • AstraZeneca

    Investigators

    • Principal Investigator: David R Spigel, MD, SCRI Development Innovations, LLC

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    AstraZeneca
    ClinicalTrials.gov Identifier:
    NCT02087241
    Other Study ID Numbers:
    • D6011C00002
    First Posted:
    Mar 14, 2014
    Last Update Posted:
    Mar 29, 2017
    Last Verified:
    Feb 1, 2017
    Keywords provided by AstraZeneca
    Stage IV Lung Cancer
    Additional relevant MeSH terms:
    Lung Neoplasms
    Carcinoma, Non-Small-Cell Lung
    Carboplatin
    Pemetrexed
    Adavosertib

    Study Results

    Participant Flow

    Recruitment Details The study was conducted at 16 clinical sites in the United States. A total of 14 subjects were enrolled between March 19, 2014 and April 16, 2015.
    Pre-assignment Detail 22 subjects were consented; 3 subjects failed screening. The study was terminated prior to the start of screening for 5 participants. 14 participants were treated with AZD1775. The study was terminated early by the sponsor. Part 2 was not done. The 14 participants were enrolled in 4 Cohorts, designated Cohorts 1, 2, 3, and A.
    Arm/Group Title Cohort 1 Cohort 2 Cohort 3 Cohort A
    Arm/Group Description AZD1775 225 mg bid. 5 doses over 3 days (Days 1, 2, and 3 of a 21- Day Cycle)/Pemetrexed 500 mg/Carboplatin AUC 6 AZD1775 225 mg bid. 5 doses over 3 days (Days 3, 4, and 5 of a 21-Day Cycle)/Pemetrexed 500 mg/Carboplatin AUC 6. AZD1775 175 mg bid. 5 doses over 3 days (Days 3, 4, and 5 of a 21-Day Cycle)/Pemetrexed 500 mg/Carboplatin AUC 6 AZD1775 125 mg bid. 5 doses over 3 days (Days 1, 2, and 3 of a 21- Day Cycle)/Pemetrexed 400 mg/Carboplatin AUC 5
    Period Title: Overall Study
    STARTED 3 3 1 7
    COMPLETED 0 0 0 0
    NOT COMPLETED 3 3 1 7

    Baseline Characteristics

    Arm/Group Title Cohort 1 Cohort 2 Cohort 3 Cohort A Total
    Arm/Group Description AZD1775 225 mg bid. 5 doses over 3 days (Days 1, 2, and 3 of a 21- Day Cycle)/Pemetrexed 500 mg/Carboplatin AUC 6 AZD1775 225 mg bid. 5 doses over 3 days (Days 3, 4, and 5 of a 21-Day Cycle)/Pemetrexed 500 mg/Carboplatin AUC 6. AZD1775 175 mg bid. 5 doses over 3 days (Days 3, 4, and 5 of a 21-Day Cycle)/Pemetrexed 500 mg/Carboplatin AUC 6 AZD1775 125 mg bid. 5 doses over 3 days (Days 1, 2, and 3 of a 21- Day Cycle)/Pemetrexed 400 mg/Carboplatin AUC 5 Total of all reporting groups
    Overall Participants 3 3 1 7 14
    Age (Years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [Years]
    65.3
    (6.03)
    59.0
    (4.36)
    81.0
    (0)
    62.6
    (9.41)
    63.7
    (8.88)
    Age (Years) [Median (Full Range) ]
    Median (Full Range) [Years]
    66.0
    61.0
    81.0
    64.0
    63.0
    Age, Customized (Number) [Number]
    < 65
    1
    33.3%
    3
    100%
    0
    0%
    4
    57.1%
    8
    57.1%
    >= 65
    2
    66.7%
    0
    0%
    1
    100%
    3
    42.9%
    6
    42.9%
    Sex: Female, Male (Count of Participants)
    Female
    2
    66.7%
    3
    100%
    0
    0%
    3
    42.9%
    8
    57.1%
    Male
    1
    33.3%
    0
    0%
    1
    100%
    4
    57.1%
    6
    42.9%
    Ethnicity (NIH/OMB) (Count of Participants)
    Hispanic or Latino
    0
    0%
    1
    33.3%
    0
    0%
    0
    0%
    1
    7.1%
    Not Hispanic or Latino
    3
    100%
    2
    66.7%
    1
    100%
    7
    100%
    13
    92.9%
    Unknown or Not Reported
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Race (NIH/OMB) (Count of Participants)
    American Indian or Alaska Native
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Asian
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Native Hawaiian or Other Pacific Islander
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Black or African American
    0
    0%
    0
    0%
    0
    0%
    1
    14.3%
    1
    7.1%
    White
    3
    100%
    3
    100%
    1
    100%
    6
    85.7%
    13
    92.9%
    More than one race
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Unknown or Not Reported
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Region of Enrollment (Number) [Number]
    United States
    3
    100%
    3
    100%
    1
    100%
    7
    100%
    14
    100%
    Tobacco Use (Number) [Number]
    Smoker
    3
    100%
    3
    100%
    1
    100%
    7
    100%
    14
    100%
    Non-Smoker
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    ECOG Performance Status (Number) [Number]
    ECOG Performance Status = 0
    1
    33.3%
    1
    33.3%
    1
    100%
    3
    42.9%
    6
    42.9%
    ECOG Performance Status = 1
    2
    66.7%
    2
    66.7%
    0
    0%
    4
    57.1%
    8
    57.1%

    Outcome Measures

    1. Primary Outcome
    Title Progression Free Survival
    Description Progression free survival is defined as the time from randomisation until the date of objective disease progression or death (by any cause in the absence of progression) regardless of whether the subject withdraws from randomised therapy or receives another anti-cancer therapy prior to progression.
    Time Frame 6 months

    Outcome Measure Data

    Analysis Population Description
    Progression-Free Survival data were not collected.
    Arm/Group Title Cohort 1 Cohort 2 Cohort 3 Cohort A
    Arm/Group Description AZD1775 225 mg bid. 5 doses over 3 days (Days 1, 2, and 3 of a 21-Day Cycle)/Pemetrexed 500 mg/Carboplatin AUC 6. AZD1775 225 mg bid. 5 doses over 3 days (Days 3, 4, and 5 of a 21-Day Cycle)/Pemetrexed 500 mg/Carboplatin AUC 6. AZD1775 175 mg bid. 5 doses over 3 days (Days 3, 4, and 5 of a 21-Day Cycle)/Pemetrexed 500 mg/Carboplatin AUC 6 AZD1775 125 mg bid. 5 doses over 3 days (Days 1, 2, and 3 of a 21- Day Cycle)/Pemetrexed 400 mg/Carboplatin AUC 5
    Measure Participants 0 0 0 0
    2. Secondary Outcome
    Title Assess the Objective Response Rates in Each Arm
    Description The objective response rate is defined as the number of the subjects with a confirmed best overall response of CR or PR divided by the number of subjects in the Full Analysis Set (FAS) for whom measureable disease is present at baseline
    Time Frame Up to a maximum of 4 treatment cycles (treatment cycles will be repeated every 21 days)

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Cohort 1 Cohort 2 Cohort 3 Cohort A
    Arm/Group Description AZD1775 225 mg bid. 5 doses over 3 days (Days 1, 2, and 3 of a 21-Day Cycle)/Pemetrexed 500 mg/Carboplatin AUC 6. AZD1775 225 mg bid. 5 doses over 3 days (Days 3, 4, and 5 of a 21- Day Cycle)/Pemetrexed 500 mg/Carboplatin AUC 6 AZD1775 175 mg bid. 5 doses over 3 days (Days 3, 4, and 5 of a 21-Day Cycle)/Pemetrexed 500 mg/Carboplatin AUC 6 AZD1775 125 mg bid. 5 doses over 3 days (Days 1, 2, and 3 of a 21- Day Cycle)/Pemetrexed 400 mg/Carboplatin AUC 5
    Measure Participants 3 3 1 7
    Number (90% Confidence Interval) [Percentage of Participants]
    66.7
    2223.3%
    33.3
    1110%
    0
    0%
    14.3
    204.3%
    3. Secondary Outcome
    Title Assess the Disease Control Rate in Each Treatment Arm
    Description the disease control rate is defined as the percentage of FAS subjects with a best overall response of CR, PR or SD).
    Time Frame Up to a maximum of 4 treatment cycles (treatment cycles will be repeated every 21 days)

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Cohort 1 Cohort 2 Cohort 3 Cohort A
    Arm/Group Description AZD1775 225 mg bid. 5 doses over 3 days (Days 1, 2, and 3 of a 21- Day Cycle)/Pemetrexed 500 mg/Carboplatin AUC 6 AZD1775 225 mg bid. 5 doses over 3 days (Days 3, 4, and 5 of a 21-Day Cycle)/Pemetrexed 500 mg/Carboplatin AUC 6. AZD1775 175 mg bid. 5 doses over 3 days (Days 3, 4, and 5 of a 21-Day Cycle)/Pemetrexed 500 mg/Carboplatin AUC 6 AZD1775 125 mg bid. 5 doses over 3 days (Days 1, 2, and 3 of a 21-Day cycle)/Pemetrexed 400 mg/Carboplatin AUC 5
    Measure Participants 3 3 1 7
    Number (90% Confidence Interval) [Percentage of Participants]
    66.7
    2223.3%
    66.7
    2223.3%
    0
    0%
    85.7
    1224.3%
    4. Secondary Outcome
    Title Assess the Duration of Response in Each Treatment Arm
    Description Duration of response is defined as the time from the date of first documented response until the date of documented progression or any cause death.
    Time Frame Up to a maximum of 4 treatment cycles (treatment cycles will be repeated every 21 days)

    Outcome Measure Data

    Analysis Population Description
    Duration of response data were not collected.
    Arm/Group Title Cohort 1 Cohort 2 Cohort 3 Cohort A
    Arm/Group Description AZD1775 225 mg bid. 5 doses over 3 days (Days 1, 2, and 3 of a 21- Day Cycle)/Pemetrexed 500 mg/Carboplatin AUC 6 AZD1775 225 mg bid. 5 doses over 3 days (Days 3, 4, and 5 of a 21-Day Cycle)/Pemetrexed 500 mg/Carboplatin AUC 6. AZD1775 175 mg bid. 5 doses over 3 days (Days 3, 4, and 5 of a 21-Day Cycle)/Pemetrexed 500 mg/Carboplatin AUC 6 AZD1775 125 mg bid. 5 doses over 3 days (Days 1, 2, and 3 of a 21-Day Cycle)/Pemetrexed 400 mg/Carboplatin AUC 5.
    Measure Participants 0 0 0 0
    5. Secondary Outcome
    Title Assess Overall Survival in Each Treatment Arm
    Description Overall survival is defined as the time from the date of randomization until death due to any cause.
    Time Frame Up to a maximum of 4 treatment cycles (treatment cycles will be repeated every 21 days)

    Outcome Measure Data

    Analysis Population Description
    Overall Survival (OS) data were not collected.
    Arm/Group Title Cohort 1 Cohort 2 Cohort 3 Cohort A
    Arm/Group Description AZD1775 225 mg bid. 5 doses over 3 days (Days 1, 2, and 3 of a 21- Day Cycle)/Pemetrexed 500 mg/Carboplatin AUC 6 AZD1775 225 mg bid. 5 doses over 3 days (Days 3, 4, and 5 of a 21-Day Cycle)/Pemetrexed 500 mg/Carboplatin AUC 6. AZD1775 175 mg bid. 5 doses over 3 days (Days 3, 4, and 5 of a 21-Day Cycle)/Pemetrexed 500 mg/Carboplatin AUC 6 AZD1775 125 mg bid. 5 doses over 3 days (Days 1, 2, and 3 of a 21-Day Cycle)/Pemetrexed 400 mg/Carboplatin AUC 5.
    Measure Participants 0 0 0 0

    Adverse Events

    Time Frame 1 year, 3 months
    Adverse Event Reporting Description Adverse event data were collected from the time the first patient received the first dose of investigational drug on March 19, 2014 until the study was closed on June 1, 2015.
    Arm/Group Title Cohort 1 Cohort 2 Cohort 3 Cohort A
    Arm/Group Description AZD1775 225 mg bid. 5 doses over 3 days (Days 1, 2, and 3 of a 21- Day Cycle)/Pemetrexed 500 mg/Carboplatin AUC 6 AZD1775 225 mg bid. 5 doses over 3 days (Days 3, 4, and 5 of a 21-Day Cycle)/Pemetrexed 500 mg/Carboplatin AUC 6. AZD1775 175 mg bid. 5 doses over 3 days (Days 3, 4, and 5 of a 21-Day Cycle)/Pemetrexed 500 mg/Carboplatin AUC 6 AZD1775 125 mg bid. 5 doses over 3 days (Days 1, 2, and 3 of a 21-Day Cycle)/Pemetrexed 400 mg/Carboplatin AUC 5.
    All Cause Mortality
    Cohort 1 Cohort 2 Cohort 3 Cohort A
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total / (NaN) / (NaN) / (NaN) / (NaN)
    Serious Adverse Events
    Cohort 1 Cohort 2 Cohort 3 Cohort A
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 1/3 (33.3%) 3/3 (100%) 1/1 (100%) 3/7 (42.9%)
    Blood and lymphatic system disorders
    FEBRILE NEUTROPENIA 0/3 (0%) 0 0/3 (0%) 0 0/1 (0%) 0 1/7 (14.3%) 1
    NEUTROPENIA 0/3 (0%) 0 2/3 (66.7%) 2 0/1 (0%) 0 0/7 (0%) 0
    PANCYTOPENIA 0/3 (0%) 0 1/3 (33.3%) 1 0/1 (0%) 0 0/7 (0%) 0
    THROMBOCYTOPENIA 0/3 (0%) 0 1/3 (33.3%) 1 0/1 (0%) 0 0/7 (0%) 0
    Cardiac disorders
    ATRIAL FIBRILLATION 1/3 (33.3%) 1 0/3 (0%) 0 0/1 (0%) 0 0/7 (0%) 0
    MYOCARDIAL INFARCTION 0/3 (0%) 0 0/3 (0%) 0 0/1 (0%) 0 1/7 (14.3%) 1
    Gastrointestinal disorders
    ABDOMINAL PAIN 0/3 (0%) 0 1/3 (33.3%) 1 0/1 (0%) 0 0/7 (0%) 0
    DIARRHOEA 0/3 (0%) 0 1/3 (33.3%) 1 0/1 (0%) 0 0/7 (0%) 0
    GASTROINTESTINAL HAEMORRHAGE 0/3 (0%) 0 0/3 (0%) 0 1/1 (100%) 1 0/7 (0%) 0
    STOMATITIS 0/3 (0%) 0 1/3 (33.3%) 1 0/1 (0%) 0 0/7 (0%) 0
    UPPER GASTROINTESTINAL HAEMORRHAGE 0/3 (0%) 0 1/3 (33.3%) 1 0/1 (0%) 0 0/7 (0%) 0
    VOMITING 0/3 (0%) 0 1/3 (33.3%) 1 0/1 (0%) 0 0/7 (0%) 0
    General disorders
    MUCOSAL INFLAMMATION 0/3 (0%) 0 1/3 (33.3%) 1 0/1 (0%) 0 0/7 (0%) 0
    Infections and infestations
    INFLUENZA 0/3 (0%) 0 0/3 (0%) 0 0/1 (0%) 0 1/7 (14.3%) 1
    Investigations
    PLATELET COUNT DECREASED 0/3 (0%) 0 1/3 (33.3%) 1 0/1 (0%) 0 0/7 (0%) 0
    Metabolism and nutrition disorders
    DEHYDRATION 0/3 (0%) 0 1/3 (33.3%) 1 1/1 (100%) 1 0/7 (0%) 0
    FAILURE TO THRIVE 0/3 (0%) 0 0/3 (0%) 0 0/1 (0%) 0 1/7 (14.3%) 1
    HYPOKALAEMIA 0/3 (0%) 0 1/3 (33.3%) 1 0/1 (0%) 0 0/7 (0%) 0
    Nervous system disorders
    CEREBROVASCULAR ACCIDENT 0/3 (0%) 0 0/3 (0%) 0 0/1 (0%) 0 1/7 (14.3%) 1
    Other (Not Including Serious) Adverse Events
    Cohort 1 Cohort 2 Cohort 3 Cohort A
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 3/3 (100%) 3/3 (100%) 1/1 (100%) 7/7 (100%)
    Blood and lymphatic system disorders
    ANAEMIA 2/3 (66.7%) 2 1/3 (33.3%) 5 1/1 (100%) 1 2/7 (28.6%) 3
    FEBRILE NEUTROPENIA 1/3 (33.3%) 1 0/3 (0%) 0 0/1 (0%) 0 1/7 (14.3%) 1
    LEUKOPENIA 0/3 (0%) 0 1/3 (33.3%) 4 0/1 (0%) 0 0/7 (0%) 0
    NEUTROPENIA 1/3 (33.3%) 1 1/3 (33.3%) 4 0/1 (0%) 0 3/7 (42.9%) 5
    THROMBOCYTOPENIA 2/3 (66.7%) 3 2/3 (66.7%) 8 0/1 (0%) 0 1/7 (14.3%) 1
    Cardiac disorders
    ATRIAL FIBRILLATION 0/3 (0%) 0 0/3 (0%) 0 1/1 (100%) 1 0/7 (0%) 0
    TACHYCARDIA 0/3 (0%) 0 0/3 (0%) 0 0/1 (0%) 0 1/7 (14.3%) 1
    Gastrointestinal disorders
    ABDOMINAL PAIN 0/3 (0%) 0 1/3 (33.3%) 1 1/1 (100%) 1 0/0 (NaN) 0
    ABDOMINAL PAIN UPPER 1/3 (33.3%) 1 0/3 (0%) 0 0/1 (0%) 0 0/7 (0%) 0
    DIARRHOEA 2/3 (66.7%) 4 2/3 (66.7%) 2 1/1 (100%) 1 1/7 (14.3%) 1
    DUODENITIS 0/3 (0%) 0 1/3 (33.3%) 1 0/1 (0%) 0 0/7 (0%) 0
    DYSPEPSIA 0/3 (0%) 0 1/3 (33.3%) 1 0/1 (0%) 0 1/7 (14.3%) 1
    GLOSSITIS 0/3 (0%) 0 1/3 (33.3%) 1 0/1 (0%) 0 0/7 (0%) 0
    NAUSEA 3/3 (100%) 3 1/3 (33.3%) 4 1/1 (100%) 1 2/7 (28.6%) 6
    OESOPHAGITIS 0/3 (0%) 0 1/3 (33.3%) 1 0/1 (0%) 0 0/7 (0%) 0
    VOMITING 3/3 (100%) 5 0/3 (0%) 0 1/1 (100%) 1 2/7 (28.6%) 2
    General disorders
    ASTHENIA 0/3 (0%) 0 0/3 (0%) 0 0/1 (0%) 0 1/7 (14.3%) 1
    CHEST PAIN 1/3 (33.3%) 1 0/3 (0%) 0 0/1 (0%) 0 0/7 (0%) 0
    CHILLS 0/3 (0%) 0 0/3 (0%) 0 1/1 (100%) 1 0/7 (0%) 0
    FATIGUE 1/3 (33.3%) 1 0/3 (0%) 0 1/1 (100%) 1 3/7 (42.9%) 5
    MUCOSAL INFLAMMATION 2/3 (66.7%) 2 0/3 (0%) 0 0/1 (0%) 0 0/7 (0%) 0
    OEDEMA PERIPHERAL 1/3 (33.3%) 1 1/3 (33.3%) 1 0/1 (0%) 0 0/7 (0%) 0
    PERIPHERAL SWELLING 1/3 (33.3%) 1 0/3 (0%) 0 0/1 (0%) 0 0/7 (0%) 0
    PAIN 0/3 (0%) 0 0/3 (0%) 0 0/1 (0%) 0 1/7 (14.3%) 1
    Infections and infestations
    CELLULITIS 1/3 (33.3%) 1 0/3 (0%) 0 0/1 (0%) 0 0/7 (0%) 0
    OESOPHAGEAL CANDIDIASIS 0/3 (0%) 0 1/3 (33.3%) 1 0/1 (0%) 0 0/7 (0%) 0
    ORAL CANDIDIASIS 0/3 (0%) 0 1/3 (33.3%) 2 0/1 (0%) 0 0/7 (0%) 0
    PNEUMONIA 0/3 (0%) 0 0/1 (0%) 0 0/1 (0%) 0 1/7 (14.3%) 1
    Injury, poisoning and procedural complications
    INFUSION RELATED REACTION 1/3 (33.3%) 4 0/3 (0%) 0 0/1 (0%) 0 0/7 (0%) 0
    Investigations
    BLOOD BILIRUBIN INCREASED 0/3 (0%) 0 1/3 (33.3%) 1 0/1 (0%) 0 0/7 (0%) 0
    BLOOD CREATININE INCREASED 0/3 (0%) 0 0/3 (0%) 0 1/1 (100%) 1 0/7 (0%) 0
    NEUTROPHIL COUNT DECREASED 2/3 (66.7%) 3 1/3 (33.3%) 4 0/1 (0%) 0 0/7 (0%) 0
    PLATELET COUNT DECREASED 1/3 (33.3%) 2 2/3 (66.7%) 9 0/1 (0%) 0 0/7 (0%) 0
    TROPONIN INCREASED 0/3 (0%) 0 0/3 (0%) 0 1/1 (100%) 1 0/7 (0%) 0
    WEIGHT DECREASED 1/3 (33.3%) 1 0/3 (0%) 0 0/1 (0%) 0 1/7 (14.3%) 1
    WHITE BLOOD CELL COUNT DECREASED 0/3 (0%) 0 1/3 (33.3%) 6 0/1 (0%) 0 0/7 (0%) 0
    Metabolism and nutrition disorders
    DECREASED APPETITE 1/3 (33.3%) 1 1/3 (33.3%) 1 0/1 (0%) 0 4/7 (57.1%) 4
    DEHYDRATION 2/3 (66.7%) 2 0/3 (0%) 0 0/1 (0%) 0 2/7 (28.6%) 3
    HYPERGLYCAEMIA 0/3 (0%) 0 0/3 (0%) 0 1/1 (100%) 1 0/7 (0%) 0
    HYPOCALCAEMIA 0/3 (0%) 0 1/3 (33.3%) 4 1/1 (100%) 1 0/7 (0%) 0
    HYPOKALAEMIA 0/3 (0%) 0 2/3 (66.7%) 8 0/1 (0%) 0 0/7 (0%) 0
    HYPOMAGNESAEMIA 0/3 (0%) 0 1/3 (33.3%) 4 0/1 (0%) 0 0/7 (0%) 0
    HYPONATRAEMIA 0/3 (0%) 0 1/3 (33.3%) 1 1/1 (100%) 1 0/7 (0%) 0
    HYPOPHOSPHATAEMIA 0/3 (0%) 0 1/3 (33.3%) 4 0/1 (0%) 0 0/7 (0%) 0
    Musculoskeletal and connective tissue disorders
    ARTHRALGIA 1/3 (33.3%) 2 0/3 (0%) 0 1/1 (100%) 1 0/7 (0%) 0
    BACK PAIN 0/3 (0%) 0 1/3 (33.3%) 1 0/1 (0%) 0 1/7 (14.3%) 1
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    SEBORRHOEIC KERATOSIS 0/3 (0%) 0 0/3 (0%) 0 0/1 (0%) 0 1/7 (14.3%) 1
    Nervous system disorders
    HEADACHE 0/3 (0%) 0 0/3 (0%) 0 0/1 (0%) 0 1/7 (14.3%) 1
    Psychiatric disorders
    ANXIETY 0/3 (0%) 0 1/3 (33.3%) 1 0/1 (0%) 0 1/7 (14.3%) 1
    INSOMNIA 0/3 (0%) 0 1/3 (33.3%) 1 0/1 (0%) 0 1/7 (14.3%) 1
    Renal and urinary disorders
    ACUTE KIDNEY INJURY 0/3 (0%) 0 0/3 (0%) 0 1/1 (100%) 1 0/7 (0%) 0
    CHROMATURIA 1/3 (33.3%) 1 0/3 (0%) 0 0/1 (0%) 0 0/7 (0%) 0
    DYSURIA 2/3 (66.7%) 3 0/3 (0%) 0 0/1 (0%) 0 0/7 (0%) 0
    Reproductive system and breast disorders
    VULVOVAGINAL BURNING SENSATION 1/3 (33.3%) 1 0/3 (0%) 0 0/1 (0%) 0 0/7 (0%) 0
    Respiratory, thoracic and mediastinal disorders
    COUGH 0/3 (0%) 0 0/3 (0%) 0 1/1 (100%) 1 0/7 (0%) 0
    EPISTAXIS 0/3 (0%) 0 0/3 (0%) 0 0/1 (0%) 0 1/7 (14.3%) 1
    HICCUPS 0/3 (0%) 0 0/3 (0%) 0 0/1 (0%) 0 1/7 (14.3%) 1
    PRODUCTIVE COUGH 0/3 (0%) 0 0/3 (0%) 0 0/1 (0%) 0 2/7 (28.6%) 2
    PULMONARY EMBOLISM 0/3 (0%) 0 0/3 (0%) 0 0/1 (0%) 0 1/7 (14.3%) 1
    Skin and subcutaneous tissue disorders
    ALOPECIA 0/3 (0%) 0 1/3 (33.3%) 1 0/1 (0%) 0 0/7 (0%) 0
    PRURITUS 1/3 (33.3%) 1 1/3 (33.3%) 1 0/1 (0%) 0 1/7 (14.3%) 2
    RASH 1/3 (33.3%) 1 0/3 (0%) 0 0/1 (0%) 0 0/7 (0%) 0
    RASH PAPULAR 0/3 (0%) 0 0/3 (0%) 0 0/1 (0%) 0 1/7 (14.3%) 1
    Vascular disorders
    HYPERTENSION 0/3 (0%) 0 0/3 (0%) 0 1/1 (100%) 1 0/7 (0%) 0
    HYPOTENSION 0/3 (0%) 0 0/3 (0%) 0 1/1 (100%) 1 3/7 (42.9%) 3
    PHLEBITIS SUPERFICIAL 1/3 (33.3%) 1 0/3 (0%) 0 0/1 (0%) 0 0/7 (0%) 0

    Limitations/Caveats

    The study was terminated on June 1, 2015 by the sponsor. The Primary Outcome Measure (Progression Free Survival) was not assessed and the randomised portion of the study was not done.

    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 Charles H. Davis
    Organization SCRI Development Innovations
    Phone +615-524-4341
    Email charles.davis2@scri-innovations.com
    Responsible Party:
    AstraZeneca
    ClinicalTrials.gov Identifier:
    NCT02087241
    Other Study ID Numbers:
    • D6011C00002
    First Posted:
    Mar 14, 2014
    Last Update Posted:
    Mar 29, 2017
    Last Verified:
    Feb 1, 2017