Assessment of Efficacy of AZD2281 in Platinum Sensitive Relapsed Serous Ovarian Cancer

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
AstraZeneca
ClinicalTrials.gov Identifier:
NCT00753545
First received: September 12, 2008
Last updated: February 6, 2013
Last verified: February 2013

September 12, 2008
February 6, 2013
August 2008
June 2010   (final data collection date for primary outcome measure)
Progression Free Survival (PFS) (According to Response Evaluation Criteria in Solid Tumours [RECIST]) [ Time Frame: Radiologic scans performed at baseline then every 12 weeks (+/- 1 week) for the first 60 weeks, then every 24 weeks (+/-1 week) thereafter ] [ Designated as safety issue: No ]
PFS was defined as the time from randomisation to the earlier date of radiological progression (per RECIST criteria) or death by any cause in the absence of objective progression. [Full analysis set (FAS)]
The primary objective of this study is to determine the efficacy (assessed by progression free survival [PFS]) of AZD2281 compared to placebo in this patient population [ Time Frame: Radiological tumour assessments will occur every 12 weeks ] [ Designated as safety issue: No ]
Complete list of historical versions of study NCT00753545 on ClinicalTrials.gov Archive Site
  • Overall Survival (OS) [ Time Frame: Follow up every 8 weeks post progression ] [ Designated as safety issue: No ]
    OS = time from randomisation to date of death from any cause. Patients who had not died at time of analysis were censored at last date patient was known to be alive. [FAS] There were insufficient events to calculate median OS or perform formal statistical analysis so percentage of patients who died are shown along with 95% confidence intervals.
  • Objective Response Rate (ORR) (According to RECIST) [ Time Frame: Radiologic scans performed at baseline then every 12 weeks (+/- 1 week) for the first 60 weeks, then every 24 weeks (+/-1 week) thereafter ] [ Designated as safety issue: Yes ]
    For each treatment group, the ORR was the number of Complete Response (CR) and Partial Response (PR) divided by the number of patients in the group in the FAS with measurable disease at baseline (displayed as a percentage below). Evaluable for response set
  • Disease Control Rate [ Time Frame: Radiologic scans performed at baseline then every 12 weeks (+/- 1 week) for the first 60 weeks, then every 24 weeks (+/-1 week) thereafter ] [ Designated as safety issue: No ]
    Disease control rate was defined as the percentage of patients who have at least 1 confirmed visit response of CR or PR or have demonstrated SD or NED for at least 23 weeks (ie, 24 weeks +/- 1 week) prior to any evidence of progression. [FAS]
  • Duration of Response [ Time Frame: Radiologic scans performed at baseline then every 12 weeks (+/- 1 week) for the first 60 weeks, then every 24 weeks (+/-1 week) thereafter ] [ Designated as safety issue: No ]
    Duration of response = time from assessment prior to timepoint where PR or CR confirmed (i.e. initial assessment of PR/CR), until earliest date of objective progression or death. [Responding patients only].
  • Percentage Change From Baseline in Tumour Size at Week 24 [ Time Frame: Radiologic scans performed at baseline then every 12 weeks (+/- 1week) for the first 60 weeks, then every 24 weeks (+/-1 week) thereafter ] [ Designated as safety issue: No ]
    Percentage change from baseline to Week 24 in target tumour size.
  • Best Percentage Change in Cancer Antigen 125 (CA-125) Levels [ Time Frame: CA-125 was measured at baseline then every 28 days on treatment ] [ Designated as safety issue: No ]
    Best percentage change from baseline in CA-125 level
  • Best Objective Response [ Time Frame: Radiologic scans performed at baseline then every 12 weeks (+/- 1week) for the first 60 weeks, then every 24 weeks (+/- 1 week) thereafter ] [ Designated as safety issue: No ]
    Best overall response from radiologic assessments. [FAS]
  • RECIST and CA-125 Response Separately and Combined [ Time Frame: Radiologic scans performed at baseline then every 12 weeks (+/- 1week) for the first 60 weeks, then every 24 weeks (+/- 1 week) thereafter and monthly for CA-125 measurements ] [ Designated as safety issue: No ]
    RECIST and CA-125 response separately and combined [Patients evaluable for either CA-125 response or RECIST response]
  • Time to Earlier of CA-125 or RECIST Progression [ Time Frame: Radiologic scans performed at baseline then every 12 weeks (+/- 1 week) for the first 60 weeks, then every 24 weeks (+/- 1 week) thereafter and monthly for CA-125 measurements ] [ Designated as safety issue: No ]
    Time from randomisation to the earlier date of radiological progression (per RECIST criteria) or CA-125 or death by any cause in the absence of objective progression. [FAS]
  • Improvement Rate for FACT-O Symptom Index (FOSI) [ Time Frame: Patient reported outcome questionnaire completed at baseline then every 28 days up to disease progression ] [ Designated as safety issue: No ]
    The percentage of patients with an improvement in FOSI. Improvement was defined as a change from baseline of greater than or equal to +3. [Evaluable for FOSI set]
  • Improvement Rate for Trial Outcome Index (TOI) [ Time Frame: Patient reported outcome questionnaire completed at baseline then every 28 days up to disease progression ] [ Designated as safety issue: No ]
    The percentage of patients with an improvement in TOI. Improvement was defined as a change from baseline of greater than or equal to +7. [Evaluable for TOI set]
  • Improvement Rate for Total Functional Analysis of Cancer Therapy - Ovarian (FACT-O) [ Time Frame: Patient reported outcome questionnaire completed at baseline then every 28 days up to disease progression ] [ Designated as safety issue: No ]
    The percentage of patients with an improvement in total FACT-O. Improvement was defined as a change from baseline of greater than or equal to +9. [Evaluable for FACT-O set]
  • FACT-O Symptom Index (FOSI) Time to Worsening [ Time Frame: Patient reported outcome questionnaire completed at baseline then every 28 days up to disease progression ] [ Designated as safety issue: No ]
    The time to worsening was compared between treatments for each of the TOI, FOSI and total FACT-O. [Evaluable for FOSI set]
  • Trial Outcome Index(TOI)Time to Worsening [ Time Frame: Patient reported outcome questionnaire completed at baseline then every 28 days up to disease progression ] [ Designated as safety issue: No ]
    The time to worsening was compared between treatments for each of the TOI, FOSI and total FACT-O. [Evaluable for TOI set]
  • Functional Analysis of Cancer Therapy - Ovarian (FACT-O) Time to Worsening [ Time Frame: Patient reported outcome questionnaire completed at baseline then every 28 days up to disease progression ] [ Designated as safety issue: No ]
    The time to worsening was compared between treatments for each of the TOI, FOSI and total FACT-O. [Evaluable for FACT-O set]
  • The secondary objectives of this study are to determine the efficacy of AZD2281 compared to placebo by assessment of overall survival (OS), best overall response, duration of response, Cancer antigen (CA)-125 response (Gynecologic CancerInterGroup [GCIG] [ Time Frame: CA-125 measurements will be performed every 28 daysradiological tumour assessments will be performed every 12 weeks for 1st 60 weeks and then every 24 weeks ] [ Designated as safety issue: No ]
  • Adverse events (AEs), physical examination, vital signs including blood pressure (BP), pulse, electrocardiogram (ECG) and laboratory findings including clinical chemistry, haematology and urinalysis. [ Time Frame: Safety assessments will generally be performed every 28 days ] [ Designated as safety issue: Yes ]
Not Provided
Not Provided
 
Assessment of Efficacy of AZD2281 in Platinum Sensitive Relapsed Serous Ovarian Cancer
Phase II Randomised, Double Blind, Multicentre Study to Assess the Efficacy of AZD2281 in the Treatment of Patients With Platinum Sensitive Relapsed Serous Ovarian Cancer Following Treatment With Two or More Platinum Containing Regimens

The primary purpose of this study to determine if AZD2281 is effective and well tolerated in maintaining the improvement in your cancer after previous platinum-based chemotherapy.

Not Provided
Interventional
Phase 2
Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Ovarian Cancer
  • Drug: AZD2281
    Oral 400mg bid
    Other Name: olaparib
  • Drug: matching placebo
    matching placebo bid
  • Experimental: 1
    AZD2281
    Intervention: Drug: AZD2281
  • Placebo Comparator: 2
    matching placebo
    Intervention: Drug: matching placebo

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
265
November 2012
June 2010   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • Female patients with histologically diagnosed serous ovarian cancer or recurrent serous ovarian cancer.
  • Patients must have completed at least 2 previous courses of platinum containing therapy; the patient must have been platinum sensitive to the penultimate chemo regimen.
  • For the last chemotherapy course prior to enrolment on the study, patients must have demonstrated an objective stable maintained response (partial or complete response) and this response needs to be maintained until completion of chemotherapy.
  • Patients must be treated on the study within 8 wks of completion of their final dose of the platinum containing regimen.

Exclusion Criteria:

  • Previous treatment with PARP inhibitors including AZD2281
  • Patients with low grade ovarian carcinoma.
  • Patients who have had drainage of their ascites during the final 2 cycles of their last chemotherapy regimen prior to enrolment on the study
  • Patients receiving any chemotherapy, radiotherapy (except for palliative reasons), within 2 weeks from the last dose prior to study entry (or a longer period depending on the defined characteristics of the agents used).
Female
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United States,   Australia,   Belgium,   Canada,   Czech Republic,   Estonia,   France,   Germany,   Israel,   Netherlands,   Poland,   Romania,   Russian Federation,   Spain,   Ukraine,   United Kingdom
 
NCT00753545
D0810C00019
No
AstraZeneca
AstraZeneca
Not Provided
Study Director: Jane Robertson, BSc, MBCHB, MD AstraZeneca
Principal Investigator: Prof Jonathan A Lederman University College, London
AstraZeneca
February 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP