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
  Purpose

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.


Condition Intervention Phase
Ovarian Cancer
Drug: AZD2281
Drug: matching placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by AstraZeneca:

Primary Outcome Measures:
  • 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)]


Secondary Outcome Measures:
  • 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]


Enrollment: 265
Study Start Date: August 2008
Study Completion Date: November 2012
Primary Completion Date: June 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1
AZD2281
Drug: AZD2281
Oral 400mg bid
Other Name: olaparib
Placebo Comparator: 2
matching placebo
Drug: matching placebo
matching placebo bid

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

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).
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00753545

  Hide Study Locations
Locations
United States, California
Research Site
Berkeley, California, United States
Research Site
Los Angeles, California, United States
Research Site
San Francisco, California, United States
United States, Florida
Research Site
Sunrise, Florida, United States
Research Site
West Palm Beach, Florida, United States
United States, Indiana
Research Site
Indianapolis, Indiana, United States
United States, Massachusetts
Research Site
Boston, Massachusetts, United States
United States, New York
Research Site
New York, New York, United States
United States, Rhode Island
Research Site
Providence, Rhode Island, United States
Australia, New South Wales
Research Site
Randwick, New South Wales, Australia
Australia, Queensland
Research Site
Nambour, Queensland, Australia
Research Site
South Brisbane, Queensland, Australia
Australia, South Australia
Research Site
North Terrace, South Australia, Australia
Research Site
Toorak Gardens, South Australia, Australia
Australia, Victoria
Research Site
Heidelberg, Victoria, Australia
Research Site
Parkville, Victoria, Australia
Belgium
Research Site
Brussels (jette), Belgium
Research Site
Leuven, Belgium
Canada, British Columbia
Research Site
Vancouver, British Columbia, Canada
Canada, Ontario
Research Site
Toronto, Ontario, Canada
Canada, Quebec
Research Site
Sherbrooke, Quebec, Canada
Czech Republic
Research Site
Brno, Czech Republic
Estonia
Research Site
Tallinn, Estonia
France
Research Site
Bordeaux Cedex, France
Research Site
Lyon Cedex 08, France
Research Site
Nantes,, France
Research Site
Paris, France
Research Site
Reims Cedex, France
Germany
Research Site
Dusseldorf, Germany
Research Site
Essen, Germany
Research Site
Gottingen, Germany
Research Site
Hannover, Germany
Research Site
Kiel, Germany
Research Site
Munchen, Germany
Research Site
ULM, Germany
Research Site
Wiesbaden, Germany
Israel
Research Site
Haifa, Israel
Research Site
Holon, Israel
Research Site
Jerusalem, Israel
Research Site
Nahariya, Israel
Research Site
Tel-aviv, Israel
Research Site
Tel-hashomer, Israel
Netherlands
Research Site
Amsterdam, Netherlands
Poland
Research Site
Bialystok, Poland
Research Site
Lublin, Poland
Research Site
Poznan, Poland
Research Site
Poznaniu, Poland
Research Site
Szczecin, Poland
Romania
Research Site
Baia Mare, Maramures, Romania
Research Site
Cluj-napoca, Romania
Research Site
Suceava, Romania
Russian Federation
Research Site
Barnaul, Russian Federation
Research Site
Ekaterinburg, Russian Federation
Research Site
Obninsk, Russian Federation
Research Site
Orenburg, Russian Federation
Research Site
Perm, Russian Federation
Research Site
St. Petersburg, Russian Federation
Spain
Research Site
Cordoba, Andalucia, Spain
Research Site
Barcelona, Cataluna, Spain
Research Site
Madrid, Comunidad de Madrid, Spain
Research Site
Valencia, Comunidad Valenciana, Spain
Ukraine
Research Site
Donetsk, Ukraine
Research Site
Kharkiv, Ukraine
Research Site
Kyiv, Ukraine
Research Site
Lutsk, Ukraine
Research Site
Odesa, Ukraine
Research Site
Ternopol, Ukraine
Research Site
Uzhgorod, Ukraine
United Kingdom
Research Site
Sutton, Surrey, United Kingdom
Research Site
Bebington, United Kingdom
Research Site
Dundee, United Kingdom
Research Site
Edinburgh, United Kingdom
Research Site
London, United Kingdom
Research Site
Manchester, United Kingdom
Research Site
Northwood, United Kingdom
Sponsors and Collaborators
AstraZeneca
Investigators
Study Director: Jane Robertson, BSc, MBCHB, MD AstraZeneca
Principal Investigator: Prof Jonathan A Lederman University College, London
  More Information

No publications provided by AstraZeneca

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: AstraZeneca
ClinicalTrials.gov Identifier: NCT00753545     History of Changes
Other Study ID Numbers: D0810C00019
Study First Received: September 12, 2008
Results First Received: December 7, 2012
Last Updated: February 6, 2013
Health Authority: Australia: Department of Health and Ageing Therapeutic Goods Administration
Belgium: Federal Agency for Medicinal Products and Health Products
Germany: Federal Institute for Drugs and Medical Devices
United Kingdom: Medicines and Healthcare Products Regulatory Agency
Israel: Ministry of Health
Poland: Office for Registration of Medicinal Products, Medical Devices and Biocidal Products
Romania: National Medicines Agency
Russia: Pharmacological Committee, Ministry of Health
Ukraine: State Pharmacological Center - Ministry of Health
United States: Food and Drug Administration

Keywords provided by AstraZeneca:
Serous,
Ovarian cancer,
PARP,
BRCA1,
BRCA2,
Poly(ADP ribose) polymerases,
Platinum sensitive,
Homologous Recombination Deficiency (HRD)

Additional relevant MeSH terms:
Ovarian Neoplasms
Adnexal Diseases
Endocrine Gland Neoplasms
Endocrine System Diseases
Genital Diseases, Female
Genital Neoplasms, Female
Gonadal Disorders
Neoplasms
Neoplasms by Site
Ovarian Diseases
Urogenital Neoplasms

ClinicalTrials.gov processed this record on October 23, 2014