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

• ClinicalTrials.gov Identifier: NCT00753545
• Recruitment Status: Completed
• First Posted: September 16, 2008
• Results First Posted: March 11, 2013
• Last Update Posted: March 21, 2024
• Sponsor: AstraZeneca
• Information provided by (Responsible Party): AstraZeneca

Tracking Information

• First Submitted Date: September 12, 2008
• First Posted Date: September 16, 2008
• Results First Submitted Date: December 7, 2012
• Results First Posted Date: March 11, 2013
• Last Update Posted Date: March 21, 2024
• Actual Study Start Date: August 28, 2008
• Actual Primary Completion Date: June 30, 2010 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: July 10, 2017)

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, assessed maximum up to 14 months. ]

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)]

• Original Primary Outcome Measures (submitted: September 15, 2008): 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 ]

Current Secondary Outcome Measures (submitted: July 10, 2017)

• Overall Survival (OS) [ Time Frame: Follow up every 12 weeks post progression, assessed maximum up to 90 months. ]
  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.
• 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, assessed maximum up to 14 months. ]
  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: Assessed at 24 weeks. Radiologic scans performed at baseline, week 12 (+/- 1 week) and week 24 (+/- 1 week). ]
  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, assessed maximum up to 14 months. ]
  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]. There were insufficient responses to enable conclusions to be drawn.
• 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, assessed maximum up to 14 months. ]
  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, assessed maximum up to 14 months. ]
  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, assessed maximum up to 14 months. ]
  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, assessed maximum up to 14 months. ]
  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, assessed maximum up to 14 months. ]
  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, assessed maximum up to 14 months. ]
  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, assessed maximum up to 14 months. ]
  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, assessed maximum up to 14 months. ]
  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, assessed maximum up to 14 months. ]
  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, assessed maximum up to 14 months. ]
  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, assessed maximum up to 14 months. ]
  The time to worsening was compared between treatments for each of the TOI, FOSI and total FACT-O. [Evaluable for FACT-O set]

Original Secondary Outcome Measures (submitted: September 15, 2008)

• 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 ]
• 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 ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Assessment of Efficacy of AZD2281 in Platinum Sensitive Relapsed Serous Ovarian Cancer
• 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
• Brief Summary: 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
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: Ovarian Cancer

Intervention

• Drug: AZD2281
  Tablets Oral BID
  Other Name: Olaparib, Lynparza
• Drug: matching placebo
  matching placebo bid

Study Arms

• Experimental: 1
  AZD2281
  Intervention: Drug: AZD2281
• Placebo Comparator: 2
  matching placebo
  Intervention: Drug: matching placebo

Publications *

• Tattersall A, Ryan N, Wiggans AJ, Rogozinska E, Morrison J. Poly(ADP-ribose) polymerase (PARP) inhibitors for the treatment of ovarian cancer. Cochrane Database Syst Rev. 2022 Feb 16;2(2):CD007929. doi: 10.1002/14651858.CD007929.pub4.
• Ledermann JA, Harter P, Gourley C, Friedlander M, Vergote I, Rustin G, Scott C, Meier W, Shapira-Frommer R, Safra T, Matei D, Fielding A, Bennett B, Parry D, Spencer S, Mann H, Matulonis U. Quality of life during olaparib maintenance therapy in platinum-sensitive relapsed serous ovarian cancer. Br J Cancer. 2016 Nov 22;115(11):1313-1320. doi: 10.1038/bjc.2016.348. Epub 2016 Nov 8.
• Ledermann JA, Harter P, Gourley C, Friedlander M, Vergote I, Rustin G, Scott C, Meier W, Shapira-Frommer R, Safra T, Matei D, Fielding A, Spencer S, Rowe P, Lowe E, Hodgson D, Sovak MA, Matulonis U. Overall survival in patients with platinum-sensitive recurrent serous ovarian cancer receiving olaparib maintenance monotherapy: an updated analysis from a randomised, placebo-controlled, double-blind, phase 2 trial. Lancet Oncol. 2016 Nov;17(11):1579-1589. doi: 10.1016/S1470-2045(16)30376-X. Epub 2016 Sep 9.
• Matulonis UA, Harter P, Gourley C, Friedlander M, Vergote I, Rustin G, Scott C, Meier W, Shapira-Frommer R, Safra T, Matei D, Fielding A, Spencer S, Parry D, Grinsted L, Ledermann JA. Olaparib maintenance therapy in patients with platinum-sensitive, relapsed serous ovarian cancer and a BRCA mutation: Overall survival adjusted for postprogression poly(adenosine diphosphate ribose) polymerase inhibitor therapy. Cancer. 2016 Jun 15;122(12):1844-52. doi: 10.1002/cncr.29995. Epub 2016 Apr 8.
• Ledermann J, Harter P, Gourley C, Friedlander M, Vergote I, Rustin G, Scott CL, Meier W, Shapira-Frommer R, Safra T, Matei D, Fielding A, Spencer S, Dougherty B, Orr M, Hodgson D, Barrett JC, Matulonis U. Olaparib maintenance therapy in patients with platinum-sensitive relapsed serous ovarian cancer: a preplanned retrospective analysis of outcomes by BRCA status in a randomised phase 2 trial. Lancet Oncol. 2014 Jul;15(8):852-61. doi: 10.1016/S1470-2045(14)70228-1. Epub 2014 May 31. Erratum In: Lancet Oncol. 2015 Apr;16(4):e158.
• Ledermann J, Harter P, Gourley C, Friedlander M, Vergote I, Rustin G, Scott C, Meier W, Shapira-Frommer R, Safra T, Matei D, Macpherson E, Watkins C, Carmichael J, Matulonis U. Olaparib maintenance therapy in platinum-sensitive relapsed ovarian cancer. N Engl J Med. 2012 Apr 12;366(15):1382-92. doi: 10.1056/NEJMoa1105535. Epub 2012 Mar 27.
• Yap TA, Carden CP, Kaye SB. Beyond chemotherapy: targeted therapies in ovarian cancer. Nat Rev Cancer. 2009 Mar;9(3):167-81. doi: 10.1038/nrc2583.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: March 20, 2018): 265
• Original Estimated Enrollment (submitted: September 15, 2008): 250
• Actual Study Completion Date: October 12, 2023
• Actual Primary Completion Date: June 30, 2010 (Final data collection date for primary outcome measure)

Eligibility 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).

Sex/Gender

• Sexes Eligible for Study: Female

• Ages: 18 Years to 130 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Australia, Austria, Belgium, Canada, Czechia, Estonia, France, Germany, Israel, Netherlands, Poland, Romania, Russian Federation, Spain, Ukraine, United Kingdom, United States
• Removed Location Countries: Czech Republic

Administrative Information

• NCT Number: NCT00753545
• Other Study ID Numbers: D0810C00019; 2008-003439-18 ( EudraCT Number )
• Has Data Monitoring Committee: No
• U.S. FDA-regulated Product: Not Provided

IPD Sharing Statement

• Plan to Share IPD: Yes
• Plan Description: Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All request will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
• Supporting Materials: Study Protocol
• Supporting Materials: Statistical Analysis Plan (SAP)
• Time Frame: AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please rerefer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
• Access Criteria: When a request has been approved AstraZeneca will provide access to the de-identified individual patient-level data in an approved sponsored tool . Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statements at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
• URL: https://astrazenecagroup-dt.pharmacm.com/DT/Home

• Current Responsible Party: AstraZeneca
• Original Responsible Party: James Carmichael, MD, Medical Science Director, AstraZeneca
• Current Study Sponsor: AstraZeneca
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Mika Sovak, BSc, MBCHB, MD; AstraZeneca
• Principal Investigator: Prof Jonathan A Lederman; University College, London

• PRS Account: AstraZeneca
• Verification Date: March 2024