ICEBERG 2: Study to Assess the Efficacy and Safety of a PARP Inhibitor for the Treatment of BRCA-positive Advanced Ovarian Cancer

Sponsor
AstraZeneca (Industry)
Overall Status
Completed
CT.gov ID
NCT00494442
Collaborator
KuDOS Pharmaceuticals Limited (Industry)
58
Enrollment
11
Locations
2
Arms
121.3
Actual Duration (Months)
5.3
Patients Per Site
0
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The purpose of the study is to see if the drug KU 0059436 is effective and well tolerated in treating patients with measurable BRCA1- or BRCA2-positive advanced ovarian cancer and for whom no curative therapeutic option exists.

Condition or DiseaseIntervention/TreatmentPhase
  • Drug: KU-0059436 (AZD2281)(PARP inhibitor)
  • Drug: KU-0059436 (AZD2281)(PARP inhibitor)
Phase 2

Study Design

Study Type:
Interventional
Actual Enrollment :
58 participants
Allocation:
Non-Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Phase II Open-label, Non-comparative, International, Multicentre Study to Assess the Efficacy and Safety of KU 0059436 Given Orally Twice Daily in Patients With Advanced BRCA1 or BRCA2 Associated Ovarian Cancer
Actual Study Start Date :
Jun 11, 2007
Actual Primary Completion Date :
Mar 17, 2009
Actual Study Completion Date :
Jul 20, 2017

Arms and Interventions

ArmIntervention/Treatment
Experimental: KU-0059436 (AZD2281) 100 mg BID

Drug: KU-0059436 (AZD2281)(PARP inhibitor)
oral
Other Names:
  • Olaparib
  • Experimental: KU-0059436 (AZD2281) 400 mg BID

    Drug: KU-0059436 (AZD2281)(PARP inhibitor)
    oral

    Outcome Measures

    Primary Outcome Measures

    1. Confirmed Objective Tumour Response (According to Response Evaluation Criteria In Solid Tumors (RECIST) [Baseline, every 8 also at study termination or initiation of confounding anti-cancer therapy.]

      Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by CT/MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease from baseline in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.

    Secondary Outcome Measures

    1. Clinical Benefit (CB) [End of study]

      Clinical Benefit (CB) is defined as the percentage of patients with a RECIST tumour response of confirmed complete response, partial response or stable disease for ≥8 weeks)

    2. Duration of Response [End of study]

      Duration of response to olaparib

    3. Best Percentage Change in Tumour Size [End of study]

      The best % change (reduction) from baseline in tumour size (defined as the sum of the longest diameters as measured among all target lesions).

    4. Progression-Free Survival (PFS) [End of study]

      Progression-Free Survival (PFS) is defined as the time from first dose to the earlier date of radiologic progression (as per RECIST criteria) or death by any cause in the absence of objective progression.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years to 130 Years
    Sexes Eligible for Study:
    Female
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:
    • Advanced ovarian cancer with positive BRCA1 or BRCA2 status

    • Failed at least one prior chemotherapy

    • In investigators opinion, no curative standard therapy exists

    • Measurable disease

    Exclusion Criteria:
    • Brain metastases

    • Less than 28 days since last treatment used to treat the disease

    • Considered a poor medical risk due to a serious uncontrolled disorder

    Contacts and Locations

    Locations

    SiteCityStateCountryPostal Code
    1Research SiteLos AngelesCaliforniaUnited States90048
    2Research SiteSan FranciscoCaliforniaUnited States94115
    3Research SiteBostonMassachusettsUnited States02115
    4Research SiteNew YorkNew YorkUnited States10065
    5Research SiteHoustonTexasUnited States77030
    6Research SiteMelbourne, ParkvilleAustraliaVIC 3050
    7Research SiteMelbourneAustralia3000
    8Research SiteRandwickAustralia2031
    9Research SiteKölnGermany50931
    10Research SiteHospitalet deLlobregatSpain08907
    11Research SiteLundSwedenS-221 85

    Sponsors and Collaborators

    • AstraZeneca
    • KuDOS Pharmaceuticals Limited

    Investigators

    • Study Director: James Carmichael, BSc MBChB MD FRCP, KuDOS Pharmaceuticals Limited
    • Principal Investigator: Andrew Tutt, PhD MRCP FRCR, Guy's and St Thomas's NHS Foundation Trust, London, UK

    Study Documents (Full-Text)

    None provided.

    More Information

    Additional Information:

    Publications

    None provided.
    Responsible Party:
    AstraZeneca
    ClinicalTrials.gov Identifier:
    NCT00494442
    Other Study ID Numbers:
    • KU36-58
    • D0810C00009
    First Posted:
    Jun 29, 2007
    Last Update Posted:
    Aug 1, 2018
    Last Verified:
    Jun 1, 2018

    Study Results

    Participant Flow

    Recruitment DetailsThe first patient was enrolled on June 11, 2007 and efficacy and safety data were collected up to the data cut-off of March 17, 2009. Patients were enrolled at 12 centres in 5 countries: Australia, Germany, Spain, Sweden and the USA.
    Pre-assignment DetailTwo cohorts of women with Breast Cancer gene 1 (BRCA1)- or BRCA2-associated ovarian cancer who had failed at least one prior chemotherapy in the advanced/metastatic setting, were planned to receive olaparib 100 mg bd (n= up to 24) or 400 mg bd (n= up to 40). Enrolment to 2 cohorts was sequential with the 400 mg bd cohort being recruited first.
    Arm/Group TitleOlaparib 100 mg bdOlaparib 400 mg bd
    Arm/Group Descriptionolaparib (KU-0059436; AZD2281) 100 mg oral capsules, twice dailyolaparib (KU-0059436; AZD2281) 400 mg oral capsules, twice daily
    Period Title: Overall Study
    STARTED2433
    COMPLETED717
    NOT COMPLETED1716

    Baseline Characteristics

    Arm/Group TitleOlaparib 100 mg bdOlaparib 400 mg bdTotal
    Arm/Group Descriptionolaparib (KU-0059436; AZD2281) 100 mg oral capsules, twice dailyolaparib (KU-0059436; AZD2281) 400 mg oral capsules, twice dailyTotal of all reporting groups
    Overall Participants243357
    Age (Years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [Years]
    55.6
    (8.02)
    56.8
    (10.49)
    56
    (9)
    Sex: Female, Male (Count of Participants)
    Female
    24
    100%
    33
    100%
    57
    100%
    Male
    0
    0%
    0
    0%
    0
    0%
    BRCA mutation (Count of Participants)
    BRCA1
    19
    79.2%
    21
    63.6%
    40
    70.2%
    BRCA2
    5
    20.8%
    12
    36.4%
    17
    29.8%

    Outcome Measures

    1. Primary Outcome
    TitleConfirmed Objective Tumour Response (According to Response Evaluation Criteria In Solid Tumors (RECIST)
    DescriptionPer Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by CT/MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease from baseline in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.
    Time FrameBaseline, every 8 also at study termination or initiation of confounding anti-cancer therapy.

    Outcome Measure Data

    Analysis Population Description
    PP Analysis Set (includes all enrolled patients who complete the trial schedule and medication regime without any major deviations to the protocol - this is the main analysis population, with ITT used to confirm)
    Arm/Group TitleOlaparib 100 mg bdOlaparib 400 mg bd
    Arm/Group Descriptionolaparib (KU-0059436; AZD2281) 100 mg oral capsules, twice dailyolaparib (KU-0059436; AZD2281) 400 mg oral capsules, twice daily
    Measure Participants2433
    PP Analysis Set
    3
    12.5%
    11
    33.3%
    ITT Analysis Set
    3
    12.5%
    11
    33.3%
    2. Secondary Outcome
    TitleClinical Benefit (CB)
    DescriptionClinical Benefit (CB) is defined as the percentage of patients with a RECIST tumour response of confirmed complete response, partial response or stable disease for ≥8 weeks)
    Time FrameEnd of study

    Outcome Measure Data

    Analysis Population Description
    PP Analysis Set (includes all enrolled patients who complete the trial schedule and medication regime without any major deviations to the protocol - this is the main analysis population, with ITT used to confirm)
    Arm/Group TitleOlaparib 100 mg bdOlaparib 400 mg bd
    Arm/Group Descriptionolaparib (KU-0059436; AZD2281) 100 mg oral capsules, twice dailyolaparib (KU-0059436; AZD2281) 400 mg oral capsules, twice daily
    Measure Participants2433
    Number (95% Confidence Interval) [Percentage of participants]
    45.5
    189.6%
    71.0
    215.2%
    3. Secondary Outcome
    TitleDuration of Response
    DescriptionDuration of response to olaparib
    Time FrameEnd of study

    Outcome Measure Data

    Analysis Population Description
    PP Analysis Set (includes all enrolled patients who complete the trial schedule and medication regime without any major deviations to the protocol - this is the main analysis population, with ITT used to confirm
    Arm/Group TitleOlaparib 100 mg bdOlaparib 400 mg bd
    Arm/Group Descriptionolaparib (KU-0059436; AZD2281) 100 mg oral capsules, twice dailyolaparib (KU-0059436; AZD2281) 400 mg oral capsules, twice daily
    Measure Participants2433
    Median (Full Range) [Days]
    242
    301
    4. Secondary Outcome
    TitleBest Percentage Change in Tumour Size
    DescriptionThe best % change (reduction) from baseline in tumour size (defined as the sum of the longest diameters as measured among all target lesions).
    Time FrameEnd of study

    Outcome Measure Data

    Analysis Population Description
    PP Analysis Set (includes all enrolled patients who complete the trial schedule and medication regime without any major deviations to the protocol - this is the main analysis population, with ITT used to confirm
    Arm/Group TitleOlaparib 100 mg bdOlaparib 400 mg bd
    Arm/Group Descriptionolaparib (KU-0059436; AZD2281) 100 mg oral capsules, twice dailyolaparib (KU-0059436; AZD2281) 400 mg oral capsules, twice daily
    Measure Participants2433
    Median (Full Range) [Percent change]
    -5.1
    -25.8
    5. Secondary Outcome
    TitleProgression-Free Survival (PFS)
    DescriptionProgression-Free Survival (PFS) is defined as the time from first dose to the earlier date of radiologic progression (as per RECIST criteria) or death by any cause in the absence of objective progression.
    Time FrameEnd of study

    Outcome Measure Data

    Analysis Population Description
    PP Analysis Set (includes all enrolled patients who complete the trial schedule and medication regime without any major deviations to the protocol - this is the main analysis population, with ITT used to confirm
    Arm/Group TitleOlaparib 100 mg bdOlaparib 400 mg bd
    Arm/Group Descriptionolaparib (KU-0059436; AZD2281) 100 mg oral capsules, twice dailyolaparib (KU-0059436; AZD2281) 400 mg oral capsules, twice daily
    Measure Participants2433
    Median (95% Confidence Interval) [Days]
    62.5
    226

    Adverse Events

    Time FrameFrom baseline, every visit until 30 days after last dose.
    Adverse Event Reporting Description
    Arm/Group TitleOlaparib 100 mg bdOlaparib 400 mg bd
    Arm/Group Descriptionolaparib (KU-0059436; AZD2281) 100 mg oral capsules, twice dailyolaparib (KU-0059436; AZD2281) 400 mg oral capsules, twice daily
    All Cause Mortality
    Olaparib 100 mg bdOlaparib 400 mg bd
    Affected / at Risk (%)# EventsAffected / at Risk (%)# Events
    Total10/24 (41.7%) 11/33 (33.3%)
    Serious Adverse Events
    Olaparib 100 mg bdOlaparib 400 mg bd
    Affected / at Risk (%)# EventsAffected / at Risk (%)# Events
    Total7/24 (29.2%) 12/33 (36.4%)
    Blood and lymphatic system disorders
    Neutropenia1/24 (4.2%) 1/33 (3%)
    Anaemia0/24 (0%) 1/33 (3%)
    Cardiac disorders
    Cardiac Failure Congestive1/24 (4.2%) 0/33 (0%)
    Gastrointestinal disorders
    Intestinal Obstruction0/24 (0%) 2/33 (6.1%)
    Nausea1/24 (4.2%) 2/33 (6.1%)
    Vomiting1/24 (4.2%) 2/33 (6.1%)
    Abdominal Pain1/24 (4.2%) 0/33 (0%)
    Large Intestinal Obstruction1/24 (4.2%) 1/33 (3%)
    Gastrointestinal Obstruction0/24 (0%) 1/33 (3%)
    Ileus0/24 (0%) 1/33 (3%)
    Intestinal Perforation0/24 (0%) 1/33 (3%)
    Small Intestinal Obstruction0/24 (0%) 1/33 (3%)
    General disorders
    Oedema Peripheral0/24 (0%) 1/33 (3%)
    Hepatobiliary disorders
    Bile Duct Stone0/24 (0%) 1/33 (3%)
    Infections and infestations
    Pneumonia0/24 (0%) 1/33 (3%)
    Injury, poisoning and procedural complications
    Humerus Fracture0/24 (0%) 1/33 (3%)
    Blood Pressure Increased1/24 (4.2%) 0/33 (0%)
    Metabolism and nutrition disorders
    Hyponatraemia1/24 (4.2%) 0/33 (0%)
    Dehydration0/24 (0%) 1/33 (3%)
    Hypokalaemia0/24 (0%) 1/33 (3%)
    Nervous system disorders
    Encephalopathy1/24 (4.2%) 0/33 (0%)
    Convulsion0/24 (0%) 1/33 (3%)
    Psychiatric disorders
    Mental Status Changes1/24 (4.2%) 0/33 (0%)
    Renal and urinary disorders
    Renal Failure1/24 (4.2%) 0/33 (0%)
    Renal Failure Acute0/24 (0%) 1/33 (3%)
    Respiratory, thoracic and mediastinal disorders
    Pulmonary Embolism1/24 (4.2%) 0/33 (0%)
    Respiratory Failure1/24 (4.2%) 0/33 (0%)
    Vascular disorders
    Deep Vein Thrombosis0/24 (0%) 1/33 (3%)
    Other (Not Including Serious) Adverse Events
    Olaparib 100 mg bdOlaparib 400 mg bd
    Affected / at Risk (%)# EventsAffected / at Risk (%)# Events
    Total23/24 (95.8%) 33/33 (100%)
    Blood and lymphatic system disorders
    Anaemia3/24 (12.5%) 7/33 (21.2%)
    Lymphopenia2/24 (8.3%) 0/33 (0%)
    Thrombocytopenia3/24 (12.5%) 1/33 (3%)
    Neutropenia2/24 (8.3%) 3/33 (9.1%)
    Gastrointestinal disorders
    Nausea15/24 (62.5%) 21/33 (63.6%)
    Diarrhoea7/24 (29.2%) 12/33 (36.4%)
    Abdominal Pain4/24 (16.7%) 9/33 (27.3%)
    Vomiting6/24 (25%) 11/33 (33.3%)
    Constipation6/24 (25%) 4/33 (12.1%)
    Abdominal Distension4/24 (16.7%) 6/33 (18.2%)
    Dyspepsia4/24 (16.7%) 4/33 (12.1%)
    Abdominal Pain Upper3/24 (12.5%) 3/33 (9.1%)
    Abdominal Discomfort1/24 (4.2%) 3/33 (9.1%)
    Abdominal Pain Lower0/24 (0%) 3/33 (9.1%)
    Gastrooesophageal Reflux Disease1/24 (4.2%) 3/33 (9.1%)
    Gastrointestinal Pain2/24 (8.3%) 0/33 (0%)
    Ascites0/24 (0%) 2/33 (6.1%)
    Gastritis0/24 (0%) 2/33 (6.1%)
    Rectal Haemorrhage0/24 (0%) 2/33 (6.1%)
    Salivary Hypersecretion0/24 (0%) 2/33 (6.1%)
    Stomatitis1/24 (4.2%) 2/33 (6.1%)
    Intestinal obstruction0/24 (0%) 2/33 (6.1%)
    General disorders
    Fatigue13/24 (54.2%) 17/33 (51.5%)
    Oedema Peripheral1/24 (4.2%) 6/33 (18.2%)
    Pyrexia2/24 (8.3%) 2/33 (6.1%)
    Asthenia0/24 (0%) 2/33 (6.1%)
    Infections and infestations
    Urinary Tract Infection5/24 (20.8%) 2/33 (6.1%)
    Upper Respiratory Tract Infection2/24 (8.3%) 3/33 (9.1%)
    Oral Herpes2/24 (8.3%) 0/33 (0%)
    Cellulitis0/24 (0%) 2/33 (6.1%)
    Herpes Zoster0/24 (0%) 2/33 (6.1%)
    Nasopharyngitis0/24 (0%) 2/33 (6.1%)
    Sinusitis0/24 (0%) 2/33 (6.1%)
    Injury, poisoning and procedural complications
    Contusion1/24 (4.2%) 4/33 (12.1%)
    Investigations
    Waist Circumference Increased4/24 (16.7%) 0/33 (0%)
    Haemoglobin Urine3/24 (12.5%) 0/33 (0%)
    Blood Urine Present2/24 (8.3%) 0/33 (0%)
    Gamma-Glutamyltransferase Increased0/24 (0%) 2/33 (6.1%)
    Metabolism and nutrition disorders
    Hypokalaemia2/24 (8.3%) 4/33 (12.1%)
    Hypomagnesaemia1/24 (4.2%) 4/33 (12.1%)
    Anorexia1/24 (4.2%) 3/33 (9.1%)
    Hyperkalaemia2/24 (8.3%) 0/33 (0%)
    Decreased Appetite1/24 (4.2%) 2/33 (6.1%)
    Musculoskeletal and connective tissue disorders
    Arthralgia4/24 (16.7%) 2/33 (6.1%)
    Back Pain4/24 (16.7%) 2/33 (6.1%)
    Muscle Spasms0/24 (0%) 4/33 (12.1%)
    Pain In Extremity0/24 (0%) 3/33 (9.1%)
    Flank Pain0/24 (0%) 2/33 (6.1%)
    Joint Swelling0/24 (0%) 2/33 (6.1%)
    Myalgia1/24 (4.2%) 2/33 (6.1%)
    Nervous system disorders
    Headache4/24 (16.7%) 7/33 (21.2%)
    Neuropathy Peripheral4/24 (16.7%) 1/33 (3%)
    Dizziness2/24 (8.3%) 3/33 (9.1%)
    Dysgeusia2/24 (8.3%) 1/33 (3%)
    Sinus Headache1/24 (4.2%) 2/33 (6.1%)
    Psychiatric disorders
    Insomnia1/24 (4.2%) 4/33 (12.1%)
    Depression2/24 (8.3%) 3/33 (9.1%)
    Anxiety1/24 (4.2%) 2/33 (6.1%)
    Renal and urinary disorders
    Pollakiuria2/24 (8.3%) 0/33 (0%)
    Reproductive system and breast disorders
    Pelvic Pain2/24 (8.3%) 2/33 (6.1%)
    Respiratory, thoracic and mediastinal disorders
    Dyspnoea4/24 (16.7%) 0/33 (0%)
    Cough3/24 (12.5%) 1/33 (3%)
    Dyspnoea Exertional0/24 (0%) 2/33 (6.1%)
    Oropharyngeal Pain1/24 (4.2%) 2/33 (6.1%)
    Skin and subcutaneous tissue disorders
    Rash5/24 (20.8%) 5/33 (15.2%)
    Dry Skin2/24 (8.3%) 1/33 (3%)

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

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

    The sponsor can review and comment prior to publication. In order to ensure that the Sponsor will be able to make comments and suggestions where pertinent, material for public dissemination will be submittted to the Sponsor for review at least sixty (60) days prior to submission for publication, public dissemination, or review by a publication committee

    Results Point of Contact

    Name/TitleGerard Lynch
    OrganizationAstraZeneca
    Phone
    EmailClinicalTrialTransparency@astrazeneca.com
    Responsible Party:
    AstraZeneca
    ClinicalTrials.gov Identifier:
    NCT00494442
    Other Study ID Numbers:
    • KU36-58
    • D0810C00009
    First Posted:
    Jun 29, 2007
    Last Update Posted:
    Aug 1, 2018
    Last Verified:
    Jun 1, 2018