Study to Compare the Efficacy and Safety of Olaparib When Given in Combination With Carboplatin and Paclitaxel, Compared With Carboplatin and Paclitaxel in Patients With Advanced Ovarian Cancer

• ClinicalTrials.gov Identifier: NCT01081951
• Recruitment Status: Active, not recruiting
• First Posted: March 5, 2010
• Results First Posted: December 10, 2012
• Last Update Posted: January 7, 2021
• Sponsor: AstraZeneca
• Information provided by (Responsible Party): AstraZeneca

Tracking Information

• First Submitted Date: February 26, 2010
• First Posted Date: March 5, 2010
• Results First Submitted Date: November 12, 2012
• Results First Posted Date: December 10, 2012
• Last Update Posted Date: January 7, 2021
• Actual Study Start Date: February 4, 2010
• Actual Primary Completion Date: October 10, 2011 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: December 9, 2014)

Progression Free Survival (PFS) [ Time Frame: Radiologic scans performed at weeks 9 and 18 (+/-1 week) and every 12 weeks thereafter relative to the date of randomisation until the primary analysis (approximately 20 months) ]

PFS (based on independent central review) was defined as the time from randomisation until objective disease progression as defined by Response Evaluation Criteria In Solid Tumours (RECIST) v1.1 (≥20% increase in the sum of the diameters of target lesions from minimum, clinically significant progression in non-target lesions or the presence of a new lesion) or death (by any cause in the absence of progression).

• Original Primary Outcome Measures (submitted: March 4, 2010): Progression free survival [ Time Frame: Event driven primary outcome, approx. 19 months after recruitment is open ]

Current Secondary Outcome Measures (submitted: December 9, 2014)

• Overall Survival (OS) [ Time Frame: Following disease progression, patients will be contacted every 12 weeks to assess survival status until the final analysis (approximately 50 months) ]
  OS was defined as the time from randomisation until death by any cause. Patients who had not died at the time of analysis were censored at the last date the patient was known to be alive.
• Percentage Change in Tumour Size [ Time Frame: Week 9 (+/- 1 week) ]
  The total tumour size was defined as the sum of the longest diameters of the target lesions. At week 9, the percentage change in tumour size was calculated as [(week 9 sum of target lesions - baseline sum of target lesions)/baseline sum of target lesions]*100 for each patient. Imputations were used for missing data where possible.

Original Secondary Outcome Measures (submitted: March 4, 2010)

• Percentage Change in Tumour Size [ Time Frame: 9 weeks after recruitment of the 50th patient ]
• To compare the safety and tolerability by collection of adverse events, haematology, clinical chemistry data, vital signs [ Time Frame: performed at screening, every week for the first 6 weeks then every 3 weeks thereafter until discontinuation from chemotherapy. Following chemotherapy phase, safety assessments will be performed until disease progression ]

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

Descriptive Information

• Brief Title: Study to Compare the Efficacy and Safety of Olaparib When Given in Combination With Carboplatin and Paclitaxel, Compared With Carboplatin and Paclitaxel in Patients With Advanced Ovarian Cancer
• Official Title: A Phase II Open Label Randomised Comparative Multicentre Study to Compare the Efficacy and Tolerability of Olaparib in Combination With Paclitaxel and Carboplatin Versus Paclitaxel and Carboplatin Alone in Patients With Platinum Sensitive Advanced Serous Ovarian Cancer
• Brief Summary: To compare the efficacy of olaparib in combination with paclitaxel and carboplatin (AUC4) when compared with carboplatin (AUC6) and paclitaxel alone in patients with advanced ovarian cancer.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Ovarian Cancer

Intervention

• Drug: olaparib
  Oral dose capsule 200mg BID day 1-10 of every 21 day cycle, Oral dose capsule 400mg BID continuously after completion of combination therapy
• Drug: paclitaxel
  175mg/m2 iv for 6 cycles (18 weeks) day 1 of 21 day cycle
  Other Name: Taxol
• Drug: carboplatin
  AUC6 iv for 6 cycles (18 weeks) day 1 of 21 day cycle
• Drug: paclitaxel
  175mg/m2 iv for up to 6 cycles (18 weeks)
• Drug: Drug: carboplatin
  AUC4 iv for up to 6 cycles (18 weeks)

Study Arms

• Experimental: 1
  200mg, 400mg BID - CAPSULES Olaparib paclitaxel iv and carboplatin iv
  Interventions:

  • Drug: olaparib
  • Drug: paclitaxel
  • Drug: Drug: carboplatin
• Active Comparator: 2
  paclitaxel iv and carboplatin iv
  Interventions:

  • Drug: paclitaxel
  • Drug: carboplatin

Publications *

• Gunderson CC, Moore KN. PARP inhibition in ovarian cancer: state of the science. Gynecol Oncol. 2015 Jan;136(1):8-10. doi: 10.1016/j.ygyno.2014.12.009.
• Oza AM, Cibula D, Benzaquen AO, Poole C, Mathijssen RH, Sonke GS, Colombo N, Špaček J, Vuylsteke P, Hirte H, Mahner S, Plante M, Schmalfeldt B, Mackay H, Rowbottom J, Lowe ES, Dougherty B, Barrett JC, Friedlander M. Olaparib combined with chemotherapy for recurrent platinum-sensitive ovarian cancer: a randomised phase 2 trial. Lancet Oncol. 2015 Jan;16(1):87-97. doi: 10.1016/S1470-2045(14)71135-0. Epub 2014 Dec 4. Erratum in: Lancet Oncol. 2015 Feb;16(2):e55. Lancet Oncol. 2015 Jan;16(1):e6.

Recruitment Information

• Recruitment Status: Active, not recruiting
• Actual Enrollment (submitted: September 12, 2017): 162
• Original Estimated Enrollment (submitted: March 4, 2010): 150
• Estimated Study Completion Date: December 31, 2021
• Actual Primary Completion Date: October 10, 2011 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Diagnosed with serous ovarian cancer
• Patients who have received no more than 3 previous platinum containing treatments and were progression free for at least 6 months following the end of the last platinum treatment
• At least one lesion that is suitable for accurate repeated measurements

Exclusion Criteria:

• Patients receiving any systemic anticancer chemotherapy, radiotherapy (except palliative) within two weeks from the last dose prior to study treatment
• Hypersensitivity to pre medications required for treatment with paclitaxel/carboplatin

Sex/Gender

• Sexes Eligible for Study: Female

• Ages: 18 Years to 125 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Australia, Belgium, Canada, Czechia, Germany, Italy, Japan, Netherlands, Panama, Peru, Spain, United Kingdom, United States
• Removed Location Countries: Czech Republic

Administrative Information

• NCT Number: NCT01081951
• Other Study ID Numbers: D0810C00041
• 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

• Responsible Party: AstraZeneca
• Study Sponsor: AstraZeneca
• Collaborators: Not Provided

Investigators

• Study Director: Jane Robertson, BSc, MBCHB, MD; AstraZeneca
• Principal Investigator: Amit Oza, MD; Princess Margaret Hospital, Canada

• PRS Account: AstraZeneca
• Verification Date: November 2020